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  • 1. Ahlund, Catherine
    et al.
    Pettersson, Knut
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Pulse wave analysis on fingertip arterial pressure: effects of age, gender and stressors on reflected waves and their relation to brachial and femoral artery blood flow2008In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 28, no 2, p. 86-95Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Analysis of the contour of the arterial pressure pulse (pulse wave analysis; PWA) adds information about arterial stiffness etc., beyond that obtained from absolute pressures. Peripheral pulses normally show an anterograde systolic peak and two reflected peaks: one in systole and one in diastole. The amplitudes and timings of these were estimated from finger pressure recordings in three study groups. We studied the usefulness of continuous digital pressures for PWA. METHODS: First, PWA from intra-arterial (brachial) and non-invasive finger pressure recordings was compared. Secondly, stress-induced (mental arithmetics and cold pressor test) changes in pressure pulse reflection were compared with blood flow changes in brachial and femoral arteries (ultrasound). Thirdly, the influence of age and gender on digital pulse pressures was investigated at rest and during exercise. RESULTS AND CONCLUSION: Pulse wave analysis results from brachial and digital pressures correlated strongly. Stress induced changes in systolic reflection were associated with changes in brachial artery flow patterns, whereas diastolic reflection was associated with femoral artery flow changes. At rest, age increased systolic reflection without affecting diastolic reflection. Exercise increased systolic reflection and reduced diastolic reflection more in older subjects (>40 years) than in younger (<40 years). In conclusion, PWA from continuous, digital pressure recordings is a convenient technique to study the arterial function at rest and during exposure to stressors in broad populations. The two reflected waves are differently regulated, which may indicate different anatomical origin.

  • 2. Appelberg, Jonas
    et al.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Pavlenko, Tatjana
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Lung aeration during sleep in patients with obstructive sleep apnoea2010In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 30, no 4, p. 301-307Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Previous studies have indicated that patients with obstructive sleep apnoea (OSA) have altered ventilation and lung volumes awake and the results suggest that this may be a determinant of severity of desaturations during sleep. However, little is known about regional lung aeration during sleep in patients with OSA. METHODS: Twelve patients with OSA were included in the study. Computed tomography was used to study regional lung aeration during wakefulness and sleep. Lung aeration was calculated in ml gas/g lung tissue in four different regions of interest (ROI(1-4)), along the border of the lung from ventral to dorsal. RESULTS: Lung aeration in the dorsal (dependent) lung region (ROI(4)) was lower during sleep compared to wakefulness 0.78 +/- 0.19 versus 0.88 +/- 0.19 (mean +/- SD) ml gas/g lung tissue (P = 0.005). Associations were found between awake expiratory reserve volume and change in lung aeration from wakefulness to sleep in ROI(4) (r = -0.69; P = 0.012). In addition, the change in lung aeration in the dorsal region correlated to sleep time (r = 0.69; P = 0.014) but not to time in supine position. The difference in lung aeration between inspiration and expiration (i.e. ventilation), was larger in the ventral lung region when expressed as ml gas per g lung tissue. In two patients it was noted that, during on-going obstructive apnoea, lung aeration tended to be increased rather than decreased. CONCLUSIONS: Aeration in the dorsal lung region is reduced during sleep in patients with OSA. The decrease is related to lung volume awake and to sleep time.

  • 3.
    Genberg, Margareta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Andrén, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Hedenström, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Commonly used reference values underestimate oxygen uptake in healthy, 50-year-old Swedish women.2018In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 38, no 1, p. 25-33Article in journal (Refereed)
    Abstract [en]

    Cardiopulmonary exercise testing (CPET) is the gold standard among clinical exercise tests. It combines a conventional stress test with measurement of oxygen uptake (VO2 ) and CO2 production. No validated Swedish reference values exist, and reference values in women are generally understudied. Moreover, the importance of achieved respiratory exchange ratio (RER) and the significance of breathing reserve (BR) at peak exercise in healthy individuals are poorly understood. We compared VO2 at maximal load (peakVO2 ) and anaerobic threshold (VO2@AT ) in healthy Swedish individuals with commonly used reference values, taking gender into account. Further, we analysed maximal workload and peakVO2 with regard to peak RER and BR. In all, 181 healthy, 50-year-old individuals (91 women) performed CPET. PeakVO2 was best predicted using Jones et al. (100·5%), while SHIP reference values underestimated peakVO2 most: 112·5%. Furthermore, underestimation of peakVO2 in women was found for all studied reference values (P<0·001) and was largest for SHIP: women had 128% of predicted peakVO2 , while men had 104%. PeakVO2 was similar in subjects with peak RER of 1-1·1 and RER > 1·1 (2 328·7 versus 2 176·7 ml min(-1) , P = 0·11). Lower BR (≤30%) related to significantly higher peakVO2 (P<0·001). In conclusion, peakVO2 was best predicted by Jones. All studied reference values underestimated oxygen uptake in women. No evidence for demanding RER > 1·1 in healthy individuals was found. A lowered BR is probably a normal response to higher workloads in healthy individuals.

  • 4.
    Hagman, Carina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotherapy. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Hedenström, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Emtner, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotherapy. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Measuring breathing patterns and respiratory movements with the respiratory movement measuring instrument2016In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 36, no 5, p. 414-420Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: The respiratory movement measuring instrument (RMMI) is a laser-based non-invasive technique to measure breathing patterns and respiratory movements (RMs). Little knowledge is known about the ability of the RMMI to measure breathing patterns and the correlation between RMs and breathing volumes.

    OBJECTIVES: One aim was to investigate whether the RMMI could discriminate between normal versus abdominal versus high costal breathing patterns in different body positions. A second aim was to determine the correlation between RMs and breathing volumes in different body positions.

    METHOD: Twenty adult, healthy subjects (10 women) were included in the study. The RMMI was used to study the above-mentioned breathing patterns in supine, sitting and standing positions. A subgroup of 12 subjects (6 women) simultaneously performed measurements of breathing volumes while RMs were recorded.

    RESULTS: The RMMI was able to discriminate between different breathing patterns in different body positions (P<0·001). The upper thoracic contribution to RMs in the sitting position was 47% for natural breathing, 32% for abdominal breathing and 64% for high costal breathing; similar results were found in the supine and standing positions. A strong correlation was observed between RMs as measured by the RMMI and different breathing volumes in all three body positions (Spearman's rho 0·86-1·00).

    CONCLUSION: The RMMI can be used to measure and analyse different breathing patterns in different body positions, and the correlation between measured RMs and breathing volumes is strong.

  • 5.
    Hansen, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Total atherosclerotic burden measured by magnetic resonance imaging is related to five-year decline in cognitive function2018In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 38, no 3, p. 373-377Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of this study was to explore whether total atherosclerotic burden is related to future decline in performance on cognitive tests.

    Methods: The total atherosclerotic burden (TAS) was assessed by whole‐body magnetic resonance angiography (WBMRA) in 305 subjects at age 70 in the study Prospective Investigation of Vasculature in Uppsala Seniors (PIVUS). The mini‐mental state examination (MMSE) and trail making tests (TMT) A and B were evaluated at ages 75 and 80 in 190 of those subjects. No subject with a diagnosis of dementia was included in the sample.

    Results: MMSE did not change during the 5 years of follow‐up, while TMT A and B increased by 4 and 7 s, respectively. TAS at age 70 was significantly related to the individual change in TMT B (P<0·0001) between age 75 and 80, when adjusted for sex, education level, TMT B at age 75 and Framingham score at age 70. No such relationship was seen for the change in TMT A (P = 0·10). The relationship between TAS and the change in MMSE was of borderline significance (P = 0·025).

    Conclusion: A relationship was found between the total atherosclerotic burden and future decline in performance on TMT B, highlighting a role of global atherosclerosis in the cognitive decline seen during ageing.

  • 6.
    Henriksen, Egil
    et al.
    Vastmanland Cty Hosp, Dept Clin Physiol, SE-72189 Vasteras, Sweden.
    Selmeryd, Jonas
    Vastmanland Cty Hosp, Dept Clin Physiol, SE-72189 Vasteras, Sweden.
    Hedberg, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Vastmanland Cty Hosp, Dept Clin Physiol, SE-72189 Vasteras, Sweden.
    Associations of left atrial volumes and Doppler filling indices with left atrial function in acute myocardial infarction2019In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 39, no 1, p. 85-92Article in journal (Refereed)
    Abstract [en]

    Recent findings suggest that left atrial (LA) function is more strongly related to adverse prognosis than LA volumes. We aimed to evaluate the associations between LA volumes and Doppler filling indices with LA function. Echocardiographic LA volumes (LAVs), mitral valve early (MV-E) and late (MV-A) peak flow velocities, and mitral atrioventricular plane tissue-Doppler early (TD-e ') and late (TD-a ') peak velocities were obtained in 320 patients with acute myocardial infarction (AMI) free from atrial fibrillation and more than moderate valvular disease. LA function was estimated as the LA emptying fraction (LAEF), that is 100x (LAVmax-LAVmin)/LAVmax. LA reservoir volume was calculated as LAVmax-LAVmin and LA transit volume as LV stroke volume-reservoir volume. In restricted cubic spline regression analyses with multivariable adjustment, a reduced LAEF was strongly associated with smaller reservoir volume, larger transit volume, LAVmax, LAVpreA and especially LAVmin. MV-E linearly increased with a lower LAEF, whereas MV-A decreased but only below LAEF levels of approximately 45%. The resulting E/A ratio showed a sudden increase in LAEF levels below similar to 45%. Lower TD-a ' was linearly associated with a lower LAEF. In conclusion, a reduced atrial function was associated with smaller LA reservoir volume, larger LA transit volume, lower TD-a ', a non-linear decrease in MV-A and a non-linear increase in E/A. Our findings are likely a reflection of the adaptation to sustain LV filling volume and counteracting a rise in pulmonary venous pressure in face of an enhanced LV end-diastolic pressure.

  • 7. Henriksen, Egil
    et al.
    Sundstedt, Milena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Hedberg, Pär
    Left ventricular end-diastolic geometrical adjustments during exercise in endurance athletes2008In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 28, no 2, p. 76-80Article in journal (Refereed)
    Abstract [en]

    The increase in left ventricular (LV) end-diastolic volume has recently been shown to explain more than 70% of the increase in stroke volume during upright exercise in endurance athletes. As the end-diastolic volume enhancement not could be explained by an increase in axial cavity length an augmentation in LV short-axis diameters is to be expected. To investigate LV end-diastolic geometrical alterations during exercise, 15 endurance athletes were examined using contrast exercise echocardiography. LV end-diastolic short-axis diameters were made from apical views at several LV cavity levels. From upright rest to upright exercise the LV end-diastolic internal cavity measurements increased significantly. During exercise, the LV cavity became geometrically more spherical with the largest increase in the LV end-diastolic short-axis cavity diameters in the mid and apical parts of the left ventricle. The LV internal long axis showed significant increase from rest to exercise but the absolute increase was small.

  • 8.
    Henriksson, Peter
    et al.
    Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Qing, Lu
    Karolinska Univ Hosp, Div Clin Chem, Stockholm, Sweden.
    Freyschuss, Anna
    Karolinska Univ Hosp, Dept Med, Stockholm, Sweden.
    Microvascular capillary assessment in relation to forearm blood flow2019In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 39, no 5, p. 322-326Article in journal (Refereed)
    Abstract [en]

    Objective To study whether vascular reactivity as assessed by the methods forearm blood flow (FBF) and postocclusive reactive hyperaemia (PRH) in the nail fold was related as a measure of endothelium-dependent vasodilation in the microcirculation. Methods Microvascular reactivity was assessed in forearm blood flow and in the nail fold by vital capillaroscopy of individual microvessels as postocclusive reactive hyperaemia. Vascular reactivity was assessed at baseline (n = 25) as well as after infusion of acetylcholine and of sodium nitroprusside (n = 13). We also performed a multivariate regression analysis to assess whether forearm blood flow or flow-mediated dilatation related to postocclusive reactive hyperaemia. Results This study showed a distinct microvascular response to both acetylcholine (endothelium-dependent vasodilation) and sodium nitroprusside (endothelium-independent vasodilation) during forearm blood flow assessment and postocclusive reactive hyperaemia assessment in the nail fold (n = 13). These changes were inversely related (r- = -0 center dot 57; P<0 center dot 05). Conclusions Forearm blood flow was inversely correlated to postocclusive reactive hyperaemia. Postocclusive reactive hyperaemia was shortened after infusion with both acetylcholine and sodium nitroprusside. This occurred in parallel with the expected increase in forearm blood flow, conceivably reflecting that both methods can be used to assess endothelium-dependent vasodilation in the microcirculation.

  • 9.
    Hjelmgren, Ola
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Wallenberg Lab,Dept Mol & Clin Med, Gothenburg, Sweden;Sahlgrens Univ Hosp, Dept Clin Physiol, Gothenburg, Sweden.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Prahl, Ulrica
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Wallenberg Lab,Dept Mol & Clin Med, Gothenburg, Sweden.
    Schmidt, Caroline
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Wallenberg Lab,Dept Mol & Clin Med, Gothenburg, Sweden.
    Bergstrom, Goran M. L.
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Wallenberg Lab,Dept Mol & Clin Med, Gothenburg, Sweden;Sahlgrens Univ Hosp, Dept Clin Physiol, Gothenburg, Sweden.
    Inverse association between size of the lipid-rich necrotic core and vascularization in human carotid plaques2018In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 38, no 2, p. 326-331Article in journal (Refereed)
    Abstract [en]

    Purpose: To study the relationship between the size of the lipid-rich necrotic core measured by MRI (magnetic resonance imaging) and the level of plaque vascularization measured by contrast-enhanced ultrasound, in human carotid plaques. Further, to compare the size of lipid-rich necrotic core from MRI to plaque echogenicity.

    Methods: Thirty-one subjects with carotid plaques underwent standard B-mode ultrasound, contrast-enhanced ultrasound and MRI. The lipid-rich necrotic core was quantified using MRI. Contrast-enhanced ultrasound was used to measure carotid plaque vascularization. Standard B-mode ultrasound was used to measure plaque echogenicity as greyscale median.

    Results: The amount of lipid-rich necrotic core correlated inversely with the degree of plaque vascularization (r = -0.40, P = 0.03). There were no correlations between the degree of plaque vascularization and the amount of fibrous tissue or calcifications. There were no correlations between greyscale median and the lipid-rich necrotic core, fibrous tissue or calcifications.

    Conclusions: We show that more dense plaque vascularization is associated with a lower plaque content of lipid-rich necrotic core. A large lipid-rich necrotic core and high plaque vascularization are both proposed as predictors of vulnerability, and our finding is therefore odds with some earlier observations. Our finding can be explained by the fact that the necrotic core of the plaque contains no viable tissue and therefore less of the plaque can be vascularized if the lipid-rich necrotic core is large. Our study suggests that the true relation between plaque vascularization and other indices of vulnerability is more complex than initially thought.

  • 10.
    Hjelmgren, Ola
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med,Wallenberg Lab, Gothenburg, Sweden;Sahlgrens Univ Hosp, Dept Clin Physiol, Gothenburg, Sweden.
    Schmidt, Caroline
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med,Wallenberg Lab, Gothenburg, Sweden.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Bergstrom, Goran M. L.
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med,Wallenberg Lab, Gothenburg, Sweden;Sahlgrens Univ Hosp, Dept Clin Physiol, Gothenburg, Sweden.
    Comparison between magnetic resonance imaging and B-mode ultrasound in detecting and estimating the extent of human carotid atherosclerosis2018In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 38, no 2, p. 296-303Article in journal (Refereed)
    Abstract [en]

    Background: In MRI studies of carotid plaques, ultrasound is used to find plaques, which are later imaged using MRI. The performance in plaque detection has not been compared between the modalities. The aim of the current study was to compare the performance of MRI and ultrasound in detecting carotid artery plaques and measuring extent of atherosclerosis.

    Methods: Subjects with at least one plaque (height >= 2.5mm) on ultrasound were imaged using MRI. The number of plaques and their height was measured in both modalities; plaque area and volume were analysed on ultrasound and MRI, respectively.

    Results: Thirty-eight subjects were included. MRI detected plaques in 95% of carotid arteries with a plaque height of 2.5 mm on ultrasound and in all carotid arteries with a plaque exceeding >= 2.5 mm. MRI detected 53% of the plaques with a height below 2.5mm. The plaque height measured with both techniques correlated significantly, 0.59, P<0.0001. Ultrasound-derived plaque height and plaque area correlated similarly to MRI-derived plaque volume, r = 0.52; P<0.0001 and r = 0.47; P = 0.001, respectively.

    Conclusions: We conclude that MRI has a similar sensitivity to ultrasound in finding carotid artery plaques that are 2.5 mm or higher. In smaller plaques, MRI detects fewer plaques. Multiple carotid plaques seen on ultrasound most often are a misinterpretation of the anatomy and correspond to a single plaque. Plaque height on ultrasound is comparable to plaque height on MRI and correlates fairly well with plaque volume on MRI making it an interesting proxy for plaque burden.

  • 11. Hysing, Per
    et al.
    Jonason, Tommy
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Hedberg, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Prevalence and prognostic impact of electrocardiographic abnormalities in outpatients with extracardiac artery disease2018In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 38, no 5, p. 823-829Article in journal (Refereed)
    Abstract [en]

    Identifying cardiac disease in patients with extracardiac artery disease (ECAD) is essential for clinical decision-making. Electrocardiography (ECG) is an easily accessible tool to unmask subclinical cardiac disease and to risk stratify patient with or without manifest cardiovascular disease (CV). We aimed to examine the prevalence and prognostic impact of ECG changes in outpatients with ECAD. Outpatients with carotid or lower extremity artery disease (n = 435) and community-based controls (n = 397) underwent resting ECG. The patients were followed during a median of 4.8 years for CV events (hospitalization or death caused by ischaemic heart disease, cardiac arrest, heart failure, or stroke). ECG abnormalities were classified according to the Minnesota Code. Major (33% versus 15%, P<0.001) but not minor ECG abnormalities (23% versus 26%, P = 0.42) were significantly more common in patients versus controls. During the follow-up, 141 patients experienced CV events. Both major ECG abnormalities [hazard ratio (HR) 1.58, 95% confidence interval (CI) 1.11-2.25, P = 0.012] and any ECG abnormalities (HR 1.57, 95% CI 1.06-2.33, P = 0.024) were significantly associated with CV events after adjustment for potential risk factors. In conclusion, ECG abnormalities were common in these outpatients with ECAD. Major and any ECG abnormalities were independent predictors of CV events. Addition of easily accessible ECG information might be useful in risk stratification for such patients.

  • 12.
    Högman, Marieann
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Research and Development, Gävleborg. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Lafih, Jaroslava
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Research and Development, Gävleborg.
    Meriläinen, Pekka
    Bröms, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Research and Development, Gävleborg.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Extended NO analysis in a healthy subgroup of a random sample from a Swedish population2009In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 29, no 1, p. 18-23Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: There is an interest in modelling exhaled nitric oxide (NO). Studies have shown that flow-independent NO parameters i.e. NO of the alveolar region (C(A)NO), airway wall (C(aw)NO), diffusing capacity (D(aw)NO) and flux (J(aw)NO), are altered in several disease states such as asthma, cystic fibrosis, alveolitis and chronic obsmuctive pulmonary disease (COPD). However, values from a healthy population are missing. OBJECTIVES: To calculate NO parameters in a healthy population by collecting NO values at different exhalation flow rates. METHODS: A random sample from the ECRHS II study was investigated. Among the 281 subjects that had performed a bronchial hyperreactivity (BHR)-test, FEV(1.0), IgE and NO-analyses 89 were found to be healthy. RESULTS: There were no differences in F(E)NO(0.05) or NO parameters between men and women. There were weak correlations between height and both F(E)NO(0.05) (r = 0.23, P = 0.03) and C(aw)NO (r = 0.22, P = 0.04). There was also a correlation between age and C(A)NO (r = 0.28, P = 0.007). When controlled for gender, this correlation was more powerful in women (r = 0.51, P = 0.001) but did not remain for male subjects. CONCLUSION: Extended NO analysis is a simple non-invasive tool that gives by far more information than F(E)NO(0.05). Based on our results, we suggest that the values for healthy subjects should be considered to fall between the following ranges: F(E)NO(0.05), 10-30 ppb; C(aw)NO, 50-250 ppb; D(aw)NO, 5-15 ml s(-1); J(aw)NO, 0.8-1.6 nl s(-1); and C(A)NO, 0-4 ppb. Values outside these intervals indicate the need for further investigation to exclude a state of disease.

  • 13.
    Högman, Marieann
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Research and Development, Gävleborg.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Norbäck, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Added value with extended NO analysis in atopy and asthma2011In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 31, no 4, p. 294-299Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION:

    Assessments of the usefulness of exhaled nitric oxide (NO) in the treatment of asthma have given conflicting results. It is not always obvious if atopic status has been tested in these evaluations.

    OBJECTIVES:

    The aim of the study is to use extended NO analysis to characterize subjects from a random sample populations with focus on rhinitis and asthma.

    METHODS:

    Data were extracted from the European Community Respiratory Health Survey II. A subgroup from the Uppsala site that had had their NO measured at multiple flow rates was included (n = 284). The nonlinear model for NO parameters was used. Atopy was defined as having a titre against at least one of the tested allergens ≥0·35 kU l(-1) . Bronchial responsiveness was assessed by methacholine challenge.

    RESULTS:

    Subjects with non-atopic rhinitis or non-atopic asthma could not be separated from healthy subjects regarding NO parameters. There was a gradual increase with atopy in airway diffusion rate (D(aw) NO); healthy subject 8·0 (7·3, 8·8), healthy atopic 8·8 (6·7, 11·5), atopic rhinitis 10·6 (9·0, 12·4) and atopic asthma 11·2 (9·9, 28·3) ml s(-1) [geometrical mean (CI(95%) )]. There was a correlation between bronchial responsiveness and D(aw) NO in atopic rhinitis (r = -0·41, P<0·01), and bronchial responsiveness and airway wall content of NO (C(aw) NO) in atopic asthma (r = -0·56, P<0·001).

    CONCLUSION:

    It is of importance to characterize atopic status when evaluating the association between NO and asthma. Our results indicate that the use of extended NO analysis, with particular attention to D(aw) NO and C(aw) NO, may be useful in monitoring treatment for rhinitis and asthma.

  • 14.
    Järhult, Susann J.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hall, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hyperaemic blood-flow velocities in systole and diastole relate to coronary risk in divergent ways2008In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 28, no 3, p. 189-95Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A recent study suggested blood-flow velocity in diastole during reactive hyperaemia as a major driver of flow-mediated vasodilation (FMD) of the brachial artery, also being related to cardiovascular risk factors. The present study aimed to investigate the relative importance of hyperaemic systolic and diastolic blood-flow velocity in the forearm regarding both FMD and cardiovascular risk factors. METHODS: In the Prospective Investigation of the Vasculature in Uppsala Seniors study, conducted in 1016 subjects aged 70 years, FMD, systolic and diastolic blood hyperaemic flow velocities in the brachial artery were evaluated by ultrasound. RESULTS: Hyperaemic blood-flow velocity both in systole and diastole were related to FMD (r = 0.14-0.19, P<0.0001). However, while hyperaemic systolic blood-flow velocity was related to coronary risk (Framingham risk score) in a positive way (r = 0.08, P = 0.013), diastolic blood-flow velocity was inversely related to coronary risk (r = -0.08, P = 0.016). Therefore, the systolic to diastolic hyperaemic blood-flow velocity ratio was more powerful related to coronary risk (r = 0.23, P = 0.0001). In a multiple regression model, both FMD and the systolic to diastolic hyperaemic blood-flow velocity ratio were independent predictors of coronary risk (P = 0.018 and P = 0.0001). CONCLUSION: As hyperaemic blood-flow velocities in systole and diastole in the brachial artery were related to coronary risk in divergent ways, the ratio thereof is a promising index of vascular function providing independent information regarding coronary risk when compared with FMD.

  • 15.
    Järhult, Susann J
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Hansen, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Johansson, Lars
    Astra Zeneca, R&D, Mölndal.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Brachial artery hyperemic blood flow velocity in relation to established indices of vascular function and global atherosclerosis2012In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 32, no 3, p. 227-233Article in journal (Other academic)
    Abstract [en]

    Background

    Systolic to diastolic blood flow velocity (SDFV) ratio in the Brachial artery recently proved to be related to cardiovascular risk and Carotid atherosclerosis. We hypothesized that the SDFV ratio was related to established markers of vascular function and global atherosclerosis. 

     

    Methods

    Established markers of endothelial function in forearm resistance vessels, flow-mediated vasodilation and arterial stiffness were assessed in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study including 1016 individuals aged 70. Whole body magnetic resonance angiography was performed in a random 306 of the participants. Atherosclerotic lesions were summarized in a total atherosclerotic score (TAS). Before and during hyperemia of the Brachial artery, systolic and diastolic blood flow velocities were measured by Doppler.

     

    Results

    The SDFV ratio was positively related to endothelium-independent vasodilatation, while inverse relations to flow-mediated dilation, common carotid artery distensibility and the stroke volume to pulse pressure ratio were found. Endothelium-dependent vasodilatation and total peripheral resistance index were not significantly related to the SDFV ratio.

    The SDFV ratio (p=0.015) and the blood flow increase during hyperemia (p= 0.020) were both significantly related to TAS after gender adjustment. When adjusted for the Framingham risk score, both the SDFV ratio (p= 0.057) and blood flow increase (p= 0.078) lost somewhat in significance.

     

    Conclusion

    The SDFV ratio was related to established markers of both vasodilation and arterial compliance, and to global atherosclerosis. Future larger studies have to evaluate if the SDFV ratio is related to global atherosclerosis independently of traditional risk factors.

  • 16.
    Järhult, Susann J.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Brachial artery hyperemic blood flow velocities are related to carotid atherosclerosis2009In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 29, no 5, p. 360-365Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Cardiovascular (CV) risk relates to the blood flow velocity pattern in the brachial artery during hyperemia, especially to the hyperaemic systolic to diastolic mean blood flow velocity (SDFV) ratio. Here, we investigated the relations between SDFV in the brachial artery and different characteristics of carotid atherosclerosis. MATERIAL AND METHODS: Data were collected from 1016 70-year-olds participating in the Prospective Investigation of Uppsala Seniors study. Doppler recordings of blood flow velocity during hyperemia were analysed in the brachial artery. In the carotid artery, intima-media thickness (IMT) was recorded together with an assessment of echogenicity by the Grey scale median (GSM) method in both overt plaques and in the intima-media complex (IM-GSM). RESULTS: The SDFV ratio was related to the number of carotid arteries affected by plaque (P = 0.018) and inversely to plaque echogenicity (P = 0.0003). The SDFV ratio was also related to IMT (P = 0.0022) and inversely to IM-GSM (P = 0.0001). These relations were statistically significant also after adjusting for major CV risk factors, individually as well as summarised as the Framingham risk score. CONCLUSION: Our results indicate that the hyperemic systolic to diastolic blood flow velocity ratio in the brachial artery is related to atherosclerosis in the carotid artery.

  • 17. Kesek, Milos
    et al.
    Björklund, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Jernberg, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Xue, Joel
    Englund, Anders
    Non-dipolar content of the T-wave as a measure of repolarization inhomogeneity in ST-elevation myocardial infarction2006In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 26, no 6, p. 362-370Article in journal (Refereed)
    Abstract [en]

    The non-dipolar content of the T-wave, i.e. the component of the signal, which cannot be explained by a dipolar model, has been suggested as a measure of the local repolarization inhomogeneity. Our purpose was to study the non-dipolar content of the T-wave during the initial course of ST-elevation myocardial infarction (STEMI), when local repolarization inhomogeneity presumably is markedly increased. Twelve-lead ECG was semicontinuously collected in 211 patients with STEMI, treated with a thrombolytic agent. The T-wave was processed by principal component analysis. The absolute and relative T-wave residues were used as measures of the non-dipolar content. The median values for each hour and for the entire monitoring time were computed. Changes in the parameters were closer studied in two windows, 0-10 respectively, 11-24 h after start of ECG-monitoring. The median of the absolute T-wave residue during the entire monitoring period was 25 000 units in the STEMI-group and 13 500 units in the comparison group. The median for hour 1 was 36 500 units and 28 800 units for hour 2. The decrease was greater in patients with >or=50% resolution of the ST-elevation at 60 min. The moment of change, identified by cumulative sum-method, showed no correlation to the time for 50% ST-resolution. We conclude, that patients with thrombolysed STEMI have an increased non-dipolar content of the T-wave. Resolution of the ST-elevation is associated with a decrease. The increased non-dipolar content reflects a property of the repolarization phase, which is related to but separated from the ST-elevation.

  • 18. Kesek, Milos
    et al.
    Franklin, Karl A.
    Sahlin, Carin
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Heart rate variability during sleep and sleep apnoea in a population based study of 387 women2009In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 29, no 4, p. 309-315Article in journal (Refereed)
    Abstract [en]

    Increased sympathetic activity during sleep has been suggested as a link between obstructive sleep apnoea syndrome and cardiovascular disease. Heart rate variability (HRV) is a measure of autonomic effect on the heart. Different parameters have been associated with sympathetic and parasympathetic activity. We have studied HRV in different sleep stages and related the HRV-pattern to sleep apnoea in a population-based sample of 387 women. We investigated the HRV-parameters standard deviation of all R-R intervals (SDNN), root of the averaged square of successive differences (RMSSD), low frequency component (LF), high frequency component (HF), ratio of low frequency component to high frequency component LF/HF and VSAI [variation in sympathetic activity between rapid eye movement (REM) and slow wave sleep, defined as LF(REM)-LF(SWS)]. The HRV-parameters were compared with the results of a full-night polysomnography. Hourly incidence of obstructive episodes was used for classifying the subjects into four apnoea-hypopnoea index (AHI)-groups (<5, > or =5 and <15, 15-30 and >30 events). Individual sleep stages were analysed by pooling all recordings. Women with high AHI had higher heart rate and LF/HF ratio. In subjects with AHI >30, LF/HF ratio however dropped to same level as with AHI <5. Subjects with high AHI had low VSAI. Levels of SDNN, LF and LF/HF ratio during REM and light sleep were similar to wakefulness. In slow wave sleep the parameters decreased. In conclusion, moderately increased prevalence of obstructive apnoeas was associated with signs of higher sympathetic activity. High AHI was however associated with a HRV-pattern suggestive of depressed sympathetic drive and lowered ability to increase it during REM.

  • 19. Koefoed-Nielsen, Jacob
    et al.
    Hansen, Lars Kjaersgaard
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Does a solitary lobar collapse give pressure-lung volume relationship similar to that found in acute respiratory distress syndrome? A porcine experimental study2008In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 28, no 6, p. 391-397Article in journal (Refereed)
    Abstract [en]

    Background: 

    The underlying pathophysiology causing different shapes of static pressure–lung volume (PV) curves is not fully elucidated. In this study the aim was to examine the influence of a solitary lobar collapse on inflation–deflation PV curves. The hypothesis was that a lobar collapse would induce the same changes in the PV-curve as those found in experimental acute lung injury (ALI) and in acute respiratory distress syndrome (ARDS).

    Methods: 

    In four mechanically ventilated, anaesthetized pigs, the right lower lobe was collapsed by selective lavage and exsufflation. End-expiratory lung volume and static inflation–deflation PV curves of the respiratory system, the chest wall and the lung were obtained before formation of the collapse. After creation of the collapse, the same measurements were performed in the non-collapsed lung and in the whole lung including the lobar collapse. In two animals computed tomography was performed to verify the lobar collapse.

    Results: 

    The solitary lobar collapse changed the PV curve by inducing a significant hysteresis and a right shift of lower inflexion point (LIP) on the inflation limb, but had minimal influence on the deflation limb. After creation of the lobar collapse, LIP was found at the pressure at which the collapse started to expand.

    Conclusions: 

    PV curves of lungs with solitary lobar collapse are similar to those found in ALI/ARDS. Inspiratory LIP indicated start of recruitment, and expiratory curves did not indicate the pressure at which collapse occurred.

  • 20.
    Kullberg, Joel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    von Below, Catrin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Lönn, Lars
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Practical approach for estimation of subcutaneous and visceral adipose tissue2007In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 27, no 3, p. 148-153Article in journal (Refereed)
    Abstract [en]

    Objectives: The first objective was to investigate the correlations between anthropometrical measurements and visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) in two cohorts differing in age using magnetic resonance imaging (MRI) as reference. A second objective was to investigate the potential usage of abdominal diameters in practical estimation of adipose tissue compartments using these cohorts. Methods: Measurements of body mass index, waist circumference, sagittal abdominal diameter (sagittal AD) and transverse abdominal diameter (transverse AD) were obtained from 336 volunteers of age 14-70 years. Manual measurements of VAT and SAT from single slice MRI at the L4-L5 level were used as reference. The abdominal diameters were measured from the MR images. Linear correlations between the anthropometrical measurements and the reference were studied. Results: Sagittal AD showed the strongest correlation to VAT (r > 0·780, P<0·0001) and transverse AD was found to give information about the amount of SAT (r > 0·866, P<0·0001). The ellipse spanned by the sagittal AD and the transverse AD was strongly correlated to the total amount of adipose tissue (r ≥ 0·962 P<0·0001). Conclusion: Strong correlations were found between sagittal and transverse abdominal diameters, assessed using MRI, and VAT and SAT, respectively. These results suggest the use of abdominal diameters in practical estimations of VAT and SAT depots.

  • 21.
    Lattuada, Marco
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Maripuu, Enn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Medical Physics.
    Hård af Segerstad, Carl
    Lundqvist, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Evaluating abdominal oedema during experimental sepsis using an isotope technique2012In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 32, no 3, p. 197-204Article in journal (Refereed)
    Abstract [en]

    Purpose: Abdominal oedema is common in sepsis. A technique for the study of such oedema may guide in the fluid regime of these patients.

    Procedures: We modified a double-isotope technique to evaluate abdominal organ oedema and fluid extravasation in 24 healthy or endotoxin-exposed (septic) piglets. Two different markers were used: red blood cells (RBC) labelled with Technetium99m (99mTc) and Transferrin labelled with Indium111 (111In). Images were acquired on a dual-head gamma camera. Microscopic evaluation of tissue biopsies was performed to compare data with the isotope technique.

    Results: No 99mTc activity was measured in the plasma fraction in blood sampled after labelling. Similarly, after molecular size gel chromatography, 111In activity was exclusively found in the high molecular fraction of the plasma. Extravasation of transferrin, indicating the degree of abdominal oedema, was 4 06 times higher in the LPS group compared to the healthy controls (P< 0 0001). Abdominal free fluid, studied in 3 animals, had as high 111In activity as in plasma, but no 99mTc activity. Intestinal lymphatic vessel size was higher in LPS (3 7 +/- 1 1 lm) compared to control animals (0 6 + 0 2 lm; P< 0 001) and oedema correlated to villus diameter (R 2 = 0 918) and lymphatic diameter (R 2 = 0 758). A correlation between a normalized index of oedema formation (NI) and intra-abdominal pressure (IAP) was also found: NI = 0 46* IAP) 3 3 (R2 = 0 56).

    Conclusions: The technique enables almost continuous recording of abdominal oedema formation and may be a valuable tool in experimental research, with the potential to be applied in the clinic.

  • 22.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    A combined test of acetylcholine-mediated vasodilation of both the forearm resistance vessels and the radial artery2013In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 33, no 3, p. 206-210Article in journal (Refereed)
    Abstract [en]

    Objective To evaluate a new combined test of endothelium-dependent vasodilation (EDV) in the forearm resistance vessel and the radial artery. Methods Acetylcholine (ACh) and sodium nitroprusside (SNP) infusion in the brachial artery were used to simultaneous evaluate EDV and endothelium-independent vasodilation (EIDV) in forearm resistance vessels (plethysmography) and in the radial artery (ultrasound) in 76 healthy subjects. Brachial artery ultrasound was used to assess flow-mediated vasodilation (FMD). Results Acetylcholine induced a 4 center dot 5% (median value, P=0 center dot 0010) increase in the radial artery diameter, while SNP induced a 31 center dot 2% increase in diameter (P<0 center dot 0001). While no increase in radial artery blood flow was induced by ACh (P=0 center dot 69), an increase by 181% in radial blood flow was induced by SNP (P<0 center dot 0001). When relating the radial artery diameter data to FMD, the change in radial artery diameter induced by ACh was significantly correlated with FMD (r=0 center dot 35, P=0 center dot 013). No such relationship was seen for the diameter change induced by SNP (r=0 center dot 03, P=0 center dot 81). When relating the radial artery blood flow data to EDV and EIDV, the change in radial artery blood flow induced by ACh was significantly correlated with EDV in an inverse fashion (r=0 center dot 42, P=0 center dot 0032). No such relationship was seen for the blood flow change induced by SNP when related to EIDV (r=0 center dot 07, P=0 center dot 63). Conclusion Simultaneous measurements of blood flow in forearm vessels by plethysmography and in the radial artery by ultrasound during ACh infusion is a new way to assess EDV in both resistance and conduit arteries during one investigation.

  • 23.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    A detailed lipoprotein profile in relation to intima-media thickness and echogenicity of three major arteries2019In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 39, no 6, p. 415-421Article in journal (Refereed)
    Abstract [en]

    Objective

    To investigate differences in risk‐factor profile, with special emphasis on detailed characterization of the lipoprotein profile, for intima‐media thickness (IMT) and echogenicity of the intima‐media complex (IM‐GSM) in three major arteries: the carotid, femoral and brachial arteries.

    Methods

    IMT and IM‐GSM were measured by ultrasound in the carotid, femoral and brachial arteries in 778 subjects, all aged 75 years (50% women), in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, in which a detailed lipoprotein profile was also determined by nuclear magnetic resonance spectroscopy.

    Results

    First, IMT was considerably lower, and IM‐GSM higher, in the brachial artery compared to the other two arteries. Second, IMT and IM‐GSM in the arteries were related to each other. Third, significant different traditional risk‐factor profiles were seen for both IMT and IM‐GSM, with generally weaker relationships for IMT in the femoral and brachial arteries compared with the carotid artery. Fourth, the strength of associations between an atherogenic lipoprotein profile and IMT in the carotid artery was attenuated in the femoral artery and virtually absent in the brachial artery. Fifth, slightly different lipoprotein profiles were seen for IM‐GSM in the three arteries.

    Conclusion

    Differences between the carotid, femoral and brachial artery IMT and IM‐GSM were seen regarding the traditional risk factors, as well as the lipoprotein profile.

  • 24.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Arterial compliance and endothelium-dependent vasodilation are independently related to coronary risk in the elderly: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study2008In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 28, no 6, p. 373-7Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Measurements of both arterial compliance and endothelium-dependent vasodilation have previously been related to coronary risk factors, but not in the same study. In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, we studied the interplay between arterial compliance and endothelium-dependent vasodilation on coronary risk. METHODS: In the population-based PIVUS study (1016 subjects aged 70 years), arterial compliance was determined by ultrasound in the carotid artery, by pulse wave analysis (augmentation index) and the stroke volume to pulse pressure ratio by echocardiography, while endothelium-dependent vasodilation (EDV) was assessed by the invasive forearm technique with acetylcholine , brachial artery ultrasound [flow-mediated dilatation (FMD)] and pulse wave analysis with terbutaline provocation [change in reflection index (RI)]. RESULTS: Factor analysis disclosed three major factors. The first factor was reflecting the three arterial compliance methods, the second factor was reflecting EDV and the change in RI, while the third factor mainly was reflecting FMD. All these three factors were independently related to the Framingham risk score in multiple regression analysis (P<0.0001, P = 0.0002 and P = 0.0046, respectively). CONCLUSIONS: In conclusion, both arterial compliance and endothelium-dependent vasodilation were independently related to the Framingham risk score, suggesting that it is worthwhile to evaluate the parallel use of these two vascular characteristics in a prospective fashion.

  • 25.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Arterial stiffness, but not endothelium-dependent vasodilation, is related to a low Ankle-Brachial index2011In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 31, no 3, p. 182-187Article in journal (Refereed)
    Abstract [en]

    Background: Arterial compliance and endothelium-dependent vasodilation are two characteristics of the vessel wall. In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study we studied the relationships between arterial compliance and endothelium-dependent vasodilation versus the Ankle-Brachial index (ABI), a clinically used index of peripheral artery disease. Methods: In the population-based PIVUS study (all aged 70), arterial compliance was determined by ultrasound as the distensibility of the carotid artery and the stroke volume to pulse pressure (SV/PP) ratio by echocardiography, while endothelium-dependent vasodilation was assessed by the invasive forearm technique with acetylcholine (EDV) and brachial artery ultrasound (FMD) in 519 subjects in whom the Ankle-Brachial index was investigated. Results: After adjustments for gender and Framingham risk score, distensibility in the carotid artery and the SV/PP ratio were significantly reduced in subjects with a reduced ABI (<0·9) in both legs (n = 15, P = 0·0006 and P = 0·0003, respectively). Endothelium-dependent vasodilation was not significantly related to a reduced ABI. Conclusion: A reduced arterial compliance, but not endothelium-dependent vasodilation, was related to a low ABI in both legs after adjustment for major risk factors, suggesting that atherosclerosis in the leg arteries is associated with arterial compliance also in other parts of the vasculature.

  • 26.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Endothelium-dependent vasodilation predicts the development of the metabolic syndrome2015In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 35, no 6, p. 411-417Article in journal (Refereed)
    Abstract [en]

    Background: Different techniques to evaluate endothelium-dependent vasodilation (EDV) in resistance and conduit arteries have been described and have been associated with the occurrence of the metabolic syndrome (MetS) in cross-sectional studies. This study aimed to evaluate whether EDV in resistance and conduit arteries could predict future development of the MetS in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study. Methods: In the population-based PIVUS study (1016 subjects all aged 70 at baseline), the invasive forearm technique with acetylcholine given in the brachial artery (resistance arteries, EDV) and the brachial artery ultrasound technique with the measurement of flow-mediated dilatation (conduit artery, FMD) were evaluated. Six hundred and twenty-four subjects free of the MetS (NCEP/ATPIII criteria) at the age of 70 were reinvestigated at the age of 75. Results: During the 5-year follow-up, 109 new subjects developed the MetS. EDV, but not FMD, predicted the development of the MetS (OR 0.78 for a 1 SD increase in EDV, 95% CI 0.62-0.97, P = 0.033). Of the five components of the MetS, EDV could significantly predict the development of the glucose (P = 0.02), waist circumference (P = 0.01) and the triglyceride components (P = 0.002), but not significantly so the HDL (P = 0.09) and blood pressure components (P = 0.92). Conclusions: EDV in resistance arteries, but not in the brachial conduit artery (FMD), was a predictor of future development of the MetS, mainly by prediction of future impairments in fasting glucose, serum triglycerides and waist circumference in an elderly cohort.

  • 27.
    Lind, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Andersson, Jessika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Hansen, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Atherosclerosis measured by whole body magnetic resonance angiography and carotid artery ultrasound is related to arterial compliance, but not to endothelium-dependent vasodilation: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study2009In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 29, no 5, p. 321-9Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Arterial compliance and endothelium-dependent vasodilation are two characteristics of the vessel wall. In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, we studied the relationships between arterial compliance and endothelium-dependent vasodilation versus atherosclerosis as measured with two imaging modalities. METHODS: In the population-based PIVUS study (1016 subjects aged 70), arterial compliance was determined by ultrasound in the carotid artery and the stroke volume to pulse pressure ratio by echocardiography, while endothelium-dependent vasodilation was assessed by the invasive forearm technique with acetylcholine and brachial artery ultrasound. Intima-media thickness was evaluated by ultrasound in the carotid artery (n = 954). Stenosis in the carotid, aorta, renal, upper and lower leg arteries were determined by magnetic resonance angiography in a random subsample of 306 subjects. RESULTS: After adjustments for gender, Framingham risk score, obesity, myocardial infarction and stroke, distensibility in the carotid artery and the stroke volume to pulse pressure ratio were both significantly related to a weighted index of stenosis in the five arterial territories evaluated by magnetic resonance angiography (p<0.02 for both). Distensibility in the carotid artery (P = 0.021), but not the stroke volume to pulse pressure ratio (P = 0.08), was also significantly related to intima-media thickness. CONCLUSION: In the elderly population, atherosclerosis is mainly related to arterial compliance, but not to endothelium-dependent vasodilation in peripheral conduit or resistance vessels.

  • 28.
    Lind, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Lampa, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lifetime change in central and peripheral haemodynamics in relation to exercise capacity2019In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 39, no 4, p. 261-275Article in journal (Refereed)
    Abstract [en]

    Exercise capacity as well as many resting central and peripheral haemodynamic features declines by age. We aimed to investigate which haemodynamic features change the most during life and which change in parallel to exercise capacity. We performed a maximal bicycle exercise test with gas exchange in 103 healthy subjects (24 young, 55 middle-aged and 24 elderly). Endothelial function, arterial compliance/stiffness and heart rate variability (HRV) were evaluated, and the myocardium and carotid arteries were investigated by ultrasound. Exercise capacity declined by almost 50% over the lifespan. Several markers reflecting arterial compliance/stiffness and HRV, as well as carotid intima-media thickness (IMT), showed lifetime impairments by >100%, while markers of LV systolic function, diastolic blood pressure and carotid artery blood flow showed only minor changes with age. The decline in exercise capacity clusters closely with many other variables measured during the exercise test, but also to resting vital capacity, left ventricular end-diastolic diameter and resting gas exchange (VO2, VCO2) to a lesser degree. Resting vital capacity was closely related to exercise capacity in the middle-aged group. We conclude that many of the resting markers of central and peripheral haemodynamics declined during life, in parallel to the decline in exercise capacity. However, some haemodynamic features, such as LF/HF ratio at HRV, stiffness index beta of the carotid artery, and heart rate reserve at the exercise test, showed a more exaggerated decline, indicating that those are not closely linked to exercise capacity.

  • 29.
    Lind, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Nylander, Ruta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Endothelium-dependent vasodilation is related to the occurrence of cortical brain infarcts at MR imaging: The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study2017In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 37, no 2, p. 194-197Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Infarcts in the brain can be divided into larger cortical and smaller deep lacunar infarcts. The pathogenesis differs between these two types of infarctions.

    OBJECTIVE: This study aims to investigate the relationship between measures of endothelium-dependent vasodilation (EDV) and occurrence of cortical and lacunar infarcts in a population-based sample.

    METHODS: In the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study, 1016 subjects aged 70 were evaluated by the invasive forearm technique with acetylcholine (EDV) and brachial artery ultrasound to assess flow-mediated vasodilation (FMD). Six to seven years later MRI of the brain was performed, and the prevalence of cortical and lacunar infarcts was visually assessed in 407 randomly selected subjects.

    RESULTS: Lacunar infarcts were found in 22% and cortical infarcts in 5·9% of the subjects. EDV and FMD were both significantly related to the occurrence of cortical, but not lacunar infarcts. In a model adjusting for gender, waist circumference, body mass index, fasting blood glucose, systolic and diastolic blood pressure, HDL and LDL cholesterol, serum triglycerides, smoking, antihypertensive treatment and statin use, both EDV and FMD were independent predictors of cortical infarcts (P = 0·035 and P = 0·008, respectively).

    CONCLUSIONS: Endothelium-dependent vasodilation in both forearm resistance vessels and the brachial artery was related to the occurrence of cortical, but not lacunar, infarcts at MRI in a population-based sample independently of traditional risk factors.

  • 30.
    Lind, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Wohlin, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Andrén, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    The echogenicity of the intimamedia complex in the common carotid artery is related to insulin resistance measured by the hyperinsulinemic clamp in elderly men2013In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 33, no 2, p. 137-142Article in journal (Refereed)
    Abstract [en]

    The echogenicity of the intimamedia complex (IM-GSM) has recently been shown to be related to the echogenicity in carotid artery plaque and to predict cardiovascular (CV) mortality. The present study aims to evaluate the relationship between metabolic CV risk factors, with special emphasis on insulin resistance, and IM-GSM in the carotid artery. Carotid artery ultrasound with grey-scale median analysis of the intimamedia complex, IM-GSM, was performed in a population sample of 480 men aged 75years. In these subjects, a euglycemic hyperinsulinemic clamp to investigate insulin resistance was performed together with measurements of conventional CV risk factors at the age of 70. The metabolic syndrome (MetS) was defined by the NCEP/ATPIII-criteria. In univariate analysis, IM-GSM in the common carotid artery was inversely correlated with the intimamedia thickness (IMT), body mass index (BMI), waist/hip ratio, fasting glucose, serum triglycerides, low HDL cholesterol and insulin resistance at the clamp (r=0 center dot 24, P<0 center dot 001). In multiple regression analysis, only insulin resistance at the clamp and BMI were independently related to IM-GSM. Subjects with the MetS (22%) showed a reduced IM-GSM when compared to those without (64 +/- 20 SD versus 68 +/- 19, P<0 center dot 05). Because the echogenicity of the intimamedia complex in the carotid artery is related to obesity and insulin resistance at clamp independently of IMT, this new vascular characteristic would serve as a marker of vascular alterations induced by insulin resistance and the MetS and has the advantage to be obtainable in almost all subjects.

  • 31. Lindqvist, Per
    et al.
    Waldenström, Anders
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kazzam, Elsadig
    Right ventricular myocardial isovolumic relaxation time and pulmonary pressure2006In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 26, no 1, p. 1-8Article in journal (Refereed)
    Abstract [en]

    AIMS: Non-invasive assessment of pulmonary artery systolic pressure (PASP) has several limitations. As previously described by Burstin, the right ventricular (RV) isovolumic relaxation time (IVRt) is sensitive to changes in PASP. We therefore compared RV myocardial IVRt, derived by Doppler tissue imaging (DTI), with simultaneously measured invasive PASP. METHODS AND RESULTS: Twenty-six consecutive patients (18 males, mean age 52 +/- 12 years, range 23-75) underwent a simultaneous Doppler echocardiography, including DTI, and cardiac catheterization examination for measurement of PASP and right atrial mean pressures. IVRt was measured using the myocardial velocities by pulsed DTI at both basal and mid cavity segments of the RV free wall. As diastolic time intervals are influenced by heart rate IVRt was corrected for heart rate (IVRt/RR%). A significant correlation was found between PASP and regional IVRt/RR% at both the basal (r = 0.42, P<0.05) and mid cavity segment (r = 0.71, P<0.001). Furthermore, when only patients with normal right atrial pressures (<7 mmHg) were taken into account, the correlation coefficient improved at both basal and mid cavity segments (r = 0.74, P<0.05 and r = 0.83, P<0.01). CONCLUSION: Pulsed Doppler-derived IVRt correlates well with PASP. The use of pulsed DTI for measurement of IVRt is simple, reproducible and easy to obtain. We propose this method as an additional non-invasive tool in the assessment of PASP.

  • 32.
    Lundberg, Christina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Hansen, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology. AstraZeneca R&D, Mölndal, Sweden.
    The relationship between carotid intima-media thickness and global atherosclerosis2014In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 34, no 6, p. 457-462Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    The aim of this study was to investigate the relationship between (i) carotid intima-media thickness (CIMT) at baseline as well as (ii) change in CIMT over 5 years (ΔCIMT) and atherosclerotically induced luminal narrowing in non-coronary arterial territories assessed by whole-body magnetic resonance angiography (WBMRA).

    METHODS AND RESULTS:

    In subgroups of the Prospective Investigation of Vasculature in Uppsala Seniors (PIVUS) study, US measurements of CIMT in the common carotid arteries were analysed at 70 and 75 years and ΔCIMT was calculated (n = 272). WBMRA, assessing arterial stenosis in five different territories by which also a total atherosclerotic score (TAS) was calculated, was performed at 70 years (n = 306).

    RESULTS:

    Carotid intima-media thickness in the carotid artery at baseline was correlated with TAS (P = 0·0001) when adjusted to a set of traditional risk factors for atherosclerosis, as well as to stenosis in two of the different investigated territories (aorta and lower leg, P = 0·013 and P = 0·004), but there was no significant correlation between ΔCIMT and TAS (P = 0·41).

    CONCLUSIONS:

    In the present study, CIMT, but not ΔCIMT over 5 years, in the carotid artery was related to overall stenoses in the body, as assessed by WBMRA. These findings support CIMT as a general marker for atherosclerosis.

  • 33. Sahli, David
    et al.
    Svensson, Maria
    Lidgren, Joakim
    Ojbrandt, Kristina
    Eriksson, Jan W
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology, Diabetes and Metabolism.
    Evaluation of simple non-invasive techniques for assessment of lower extremity arterial disease.2005In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 25, no 3, p. 129-34Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate the reproducibility and precision of three, simple, non-invasive methods to measure blood pressure (BP) in the lower extremities by comparing reproducibility and sensitivity in finding abnormally low BP between ankle blood pressure (ABP) and toe blood pressure (TBP), by studying the concordance between TBP in toe 1 and 2 and evaluating the pole-pox method in patients with diabetes and lower extremity arterial disease (LEAD).

    SUBJECTS AND METHODS: The BP was measured twice, 1 week apart, in arms and legs in 13 controls and 12 patients with diabetes. ABP was assessed by using a Doppler pen for pulse registration. TBP was obtained by using a small cuff and a pulse oximetry sensor at toe 1 and 2. In eleven patients with diabetes and previously known LEAD ABP was obtained through the pole-pox method.

    RESULTS: No significant difference in reproducibility between absolute BPs and indices (coefficients of variation <9%) was found. A non-significant improvement with 4-8% in the sensitivity in detecting LEAD was seen when BP indices were used instead of absolute BP. A significant correlation in the variation over time for systemic and TBP (r = 0.34, P = 0.015) and a strong correlation was found between TBP measured at toe 1 and 2, respectively (r = 0.99, P < 0.001) was found. TBP measured with pole-pox method were significantly correlated with measurements made by the ordinary cuff technique (r = 0.75, P < 0.001).

    CONCLUSIONS: The use of TBP and ABP indices instead of absolute BP does not improve the reproducibility but may improve the sensitivity with respect to detection of LEAD, especially in patients with diabetes. The pole-pox method may be used as an alternative screening method in patients with diabetes and LEAD.

  • 34. Schmekel, Birgitta
    et al.
    Blomstrand, Peter
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Serum lysozyme a surrogate marker of pulmonary microvascular injury in smokers?2013In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 33, no 4, p. 307-312Article in journal (Refereed)
    Abstract [en]

    Progression rate of disease processes in smoke-induced lung injuries varies greatly. Diverse pathophysiological mechanisms may trigger these divergences. The aim of this study was to evaluate whether circulating markers of monocytes/macrophages and/or neutrophil [i.e. lysozyme (LZM) or myeloperoxidase (MPO)] were associated with reduced values of diffusion capacity (DL,CO), which is considered to serve as a mirror of pulmonary microvascular derangement and an early sign of tissue remodelling in smokers. Data obtained from 134 smokers (GOLD stage 1) and 24 matched healthy non-smoking volunteers were evaluated in a cross-sectional study design. Lung function tests as well as single breath test of DL,CO were assessed according to ATS/ERS guidelines. Biomarkers were measured in serum by means of sensitive immunoassays. A subgroup of smokers with normal lung function was created to minimize confounding, by excluding datasets showing significant airflow limitation and abnormally high values of carboxy haemoglobin (COHb), the latter indicating recent smoking. The capacity of serum lysozyme to correctly identify abnormally low values of DL,CO (i.e. <1 center dot 9SD units), tended to be higher than that of Myeloperoxidase as assessed by analyses of receiver operated curves (ROC; AUC 0 center dot 81, 95%CI: 0 center dot 690 center dot 89 versus AUC 0 center dot 67, 95%CI: 0 center dot 600 center dot 81). It is concluded that serum levels of lysozyme, reflecting mainly activated monocytes/macrophages but also neutrophils, were significantly associated with isolated decrements of DL,CO in smokers with normal lung function tests. This suggests monocytes/macrophages to have a significant mechanistic role in early phases of the disease process and/or pulmonary microvascular damage.

  • 35. Selmeryd, Jonas
    et al.
    Sundstedt, Milena
    Nilsson, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Henriksen, Egil
    Hedberg, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Impact of left ventricular geometry on long-term survival in elderly men and women2014In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 34, no 6, p. 442-448Article in journal (Refereed)
    Abstract [en]

    Background: Adverse loading conditions and cardiac injury lead to remodelling of the heart into different patterns of left ventricular (LV) geometry. Geometry can be classified into LV hypertrophy (LVH), concentric remodelling (CR) or normal geometry (NG). The prognostic implications of the different geometric patterns have been extensively studied in middle-aged subjects, but data are scarcer for elderly populations. Methods: From a community-based random sample of 75-year-old men and women, subjects with normal LVEF were selected (n = 303). All-cause and cardiovascular mortality was analysed by LV geometry with Cox regression (unadjusted and adjusted for sex, prevalent hypertension, smoking, diabetes and prevalent ischaemic heart disease). Median follow-up time was 9.9 years. Results: Prevalence of CR and LVH was 19% and 17%, respectively. Hazard ratios (HRs) for CR were 0.93 (95% CI 0.54-1.58) for all-cause and 1.13 (0.48-2.65) for cardiovascular mortality. HRs for LVH were 2.01 (1.30-3.10) for all-cause and 3.55 (1.89-6.67) for cardiovascular mortality. As non-proportionality was present in the form of an increasing hazard for LVH, we partitioned the follow-up time at the median event time (approximately 7 years) and performed Cox regression separately within each time period. HRs for LVH during the first period were 1.23 (0.63-2.42) for all-cause and 1.79 (0.69-4.65) for cardiovascular mortality, while HRs for the second period were 3.06 (1.73-5.41) for all-cause and 6.60 (2.82-15.39) for cardiovascular mortality. Conclusion: In this community-based sample of 75-year-old men and women with normal LVEF, LVH was associated with an adverse prognosis during long-term follow-up, whereas CR was not.

  • 36.
    Sundstedt, Milena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Hedberg, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Henriksen, Egil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Mitral annular excursion during exercise in endurance athletes2008In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 28, no 1, p. 27-31Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to quantify the left ventricular (LV) longitudinal motion during exercise at rest and during upright exercise in 24 healthy male endurance athletes. By using M-mode and two-dimensional echocardiography, the relative mitral annular motion and the absolute LV longitudinal axis was measured at end-diastole and end-systole at rest and during exercise. From rest to peak exercise at a heart rate of 160 beats per minute (bpm) the mitral annular motion increased in the septal and lateral annular borders by 68% and 49% respectively. At rest, mitral annular excursion was significantly (13%) higher in the lateral than in the septal wall but at peak exercise at a heart rate of 160 bpm there was no difference between the septal and lateral annular motion. The total end-diastolic LV axial length did not increase from rest to peak exercise. In conclusion, during upright exercise, mitral annular motion increased significantly with no difference between the septal and lateral annular excursion at peak exercise. The absolute increase in mitral annular motion during exercise was explained by a decrease in axial end-systolic length.

  • 37.
    Sundstedt, Milena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Hedberg, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Jonason, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Ringqvist, Ivar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Henriksen, Egil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Echocardiographic doppler assessments of left ventricular filling and ejection during upright exercise in endurance athletes2007In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 27, no 1, p. 36-41Article in journal (Refereed)
    Abstract [en]

    Doppler echocardiography was used to describe left ventricular filling and ejection during upright bicycle exercise in 24 healthy male endurance athletes. The transmitral pressure gradient was estimated and isovolumetric relaxation, filling and ejection time and transmitral and aortic flow velocities were measured at rest and during exercise. From rest to peak exercise (at a heart rate of 160 bpm), the mean left ventricular filling time was shortened by 73%, the ejection time by 31%, while the isovolumetric relaxation time was shortened by 62%. At peak exercise, the maximum aortic flow velocity almost doubled and the maximum transmitral flow velocity more than doubled, with a tenfold increase in the mean transmitral pressure gradient. The increase was significant (P<0·001) at each level of exercise. The left ventricular filling rate measured as volume per time was 185 ± 62 ml s−1 at rest and it increased to 986 ± 192 ml s−1 at peak exercise. This study demonstrates large changes in diastolic filling indices during upright exercise and it shows that the heart is able to increase its filling rate five times from rest to peak exercise.

  • 38.
    Sörensen, Jens
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Valind, Sven
    Andersson, Lars G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Simultaneous quantification of myocardial perfusion, oxidative metabolism, cardiac efficiency and pump function at rest and during supine bicycle exercise using 1-11C-acetate PET - a pilot study2010In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 30, no 4, p. 279-284Article in journal (Refereed)
    Abstract [en]

    Background: 

    PET using 1-11C-acetate (ACE-PET) applied at rest is used for measuring absolute myocardial blood flow (MBF) and oxidative metabolic rate (kmono). We evaluated the feasibility of quantitative ACE-PET during exercise.

    Methods: 

    Five endurance athletes underwent dynamic PET scanning at rest and during supine bicycle stress. Exercise was maintained at a workload of 120 Watt for 17 min. The rate-pressure product (RPP) was recorded repeatedly. MBF, kmono in left (LV) and right (RV) ventricular wall, cardiac output (CO), cardiac efficiency and a lung uptake value reflecting left heart diastolic pressures were calculated from the PET data using previously validated models.

    Results: 

    MBF increased from 0·71 ± 0·17 to 2·48 ± 0·25 ml min−1 per ml, LV-kmono from 0·050 ± 0·005 to 0·146 ± 0·021 min−1, RV-kmono from 0·023 + 0·006 to 0·087 + 0·014 min-1, RPP from 4·7 ± 0·8 to 13·2 ± 1·4 mmHg × min−1 × 103 and Cardiac Output from 5·2 ± 1·1 to 12·3 ± 1·2 l min −1 (all P < 0·001). Cardiac efficiency was unchanged (P = 0·99). Lung uptake decreased from 1·1 ± 0·2 to 0·6 ± 0·1 ml g−1 (P < 0·001).

    Discussion: 

    A number of important parameters related to cardiac function can be quantified non-invasively and simultaneously with a short scanning protocol during steady state supine bicycling. This might open up new opportunities for studies of the integrated cardiac physiology in health and early asymptomatic disease.

  • 39.
    Vedung, Torbjörn
    et al.
    Dept of Physiology and Pharmacology, Karolinska Institutet. Dept of Hand Surgery, Södersjukhuset. .
    Jorfeldt, Lennart
    Dept of Molecular Medicine and Surgery, Section of Clinical Physiology, Karolinska Institutet. Dept of Clinical Physiology Karolinska University Hospital.
    Henriksson, Jan
    Dept of Physiology and Pharmacology, Karolinska Institutet.
    Alterations in forearm position and environmental temperature influences the segmental volume expansion during venous occlusion plethysmography--special attention on hand circulation.2009In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 29, no 5, p. 376-81Article in journal (Refereed)
    Abstract [en]

    AIM: To find evidence that small changes in the positioning of the strain gauge, the environmental temperature (sympathetic activation) and position of the arm (venous pressure) alters the outcome of the venous occlusion plethysmography (VOP) measurement of forearm blood flow and to investigate if the hand circulation influences the results.

    METHODS: Forearm blood flow was measured with VOP (n = 6) on three occasions with air temperatures of 13, 20 and 38 degrees C, respectively. At each occasion the arm position was varied; raised by 10 degrees , horizontal or lowered by 15 degrees . Strain gauges were placed on the forearm at the maximal circumference; 5 cm distal; and 5 cm proximal to this site, respectively. The hand circulation was excluded in half of the measurements.

    RESULTS: The simple main effect of temperature was highly significant (P<0.001). With excluded hand circulation (but not when included), there was a two factor interaction between arm position - strain gauge position (P<0.05). The highest expansion rate was found in the proximal segment when the arm was elevated, but in the distal segment when the arm was lowered. With hand circulation (but not without) there was a two factor interaction between temperature and strain gauge position (P<0.01). The highest expansion rate was found in the distal segment at normal and high temperatures, but in the proximal segment at low temperature.

    CONCLUSION: The volume expansion rate in a particular segment is dependent not only on arterial inflow. Segmental differences in capacity for venous expansion results in redistribution of blood to and from a segment, thus influencing the results obtained.

  • 40.
    Vedung, Torbjörn
    et al.
    Dept of Physiology and Pharmacology, Karolinska Institutet. Dept of Hand Surgery, Södersjukhuset. .
    Jorfeldt, Lennart
    Dept of Molecular Medicine and Surgery, Section of Clinical Physiology, Karolinska Institutet. Dept of Clinical Physiology Karolinska University Hospital.
    Henriksson, Jan
    Dept of Physiology and Pharmacology, Karolinska Institutet.
    Intravenous adrenaline infusion causes vasoconstriction close to an intramuscular microdialysis catheter in humans.2010In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 30, no 6, p. 399-405Article in journal (Refereed)
    Abstract [en]

    AIM: To test if a small muscle injury influences the vascular reactivity to adrenaline in human skeletal muscle.

    METHODS: Blood flow was measured by ¹³³Xenon clearance in the gastrocnemius muscle of eight male subjects at basal and during i.v. infusion of adrenaline (0.1 nmol kg⁻¹ min⁻¹) or placebo. Measurements were done with (expts 2 and 3) or without (expt 1) the influence of a small muscle injury induced by inserting a microdialysis catheter. ¹³³Xenon was administered either (expt 1) conventionally into the muscle via a fine needle, or (expts 2 and 3) through a fine tube close to the inserted microdialysis catheter. Expt 3 (control expt) was identical to expt 2 except that placebo was infused instead of adrenaline. Mean ± SEM, n= 8.

    RESULTS:   The blood flow tended to increase during the adrenaline infusion in expt 1 (1.17 ± 0.10 to 1.39 ± 0.15, N.S.), whereas it decreased during the adrenaline infusion in expt 2, from 1.39 ± 0.14 to 1.03 ± 0.14 ml min⁻¹ 100 g tissue⁻¹ (P<0.001). The blood flow change in response to adrenaline infusion was significantly different in expt 1 and expt 2 (P<0.05). Blood flow also decreased during the placebo infusion in expt 3 (1.15 ± 0.10 to 1.00 ± 0.09, P<0.01), but this decrease was significantly smaller than in response to the adrenaline infusion in expt 2, P<0.01.

    CONCLUSION: The present results are consistent with the hypothesis that the small muscle injury caused by the inserted microdialysis catheter influences the vascular reactivity to adrenaline in a vasoconstrictive direction.

  • 41. Waldenström, Anders
    et al.
    Ronquist, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Aberg, Anna-Maja
    Ahlström, Katarina
    Hauck, Philip
    Abrahamsson, Pernilla
    Johansson, Göran
    Biber, Björn
    Haney, Michael F
    Ischaemic preconditioning reduces myocardial calcium overload in coronary-occluded pig hearts shown by continuous in vivo assessment using microdialysis2012In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 32, no 2, p. 133-138Article in journal (Refereed)
    Abstract [en]

    During ischaemia, ATP depletion leads to insufficient fuelling for Na+/K+ ATPase, decreased electrochemical potential and increased influx of calcium ions. This study demonstrated a means to assess the effects of ischaemic preconditioning (IP) on the free intracellular Ca2+ pool during prolonged ischaemia. In a porcine myocardial ischaemia model, microdialysis (MD) was used for sampling of metabolic and injury markers in IP and non-IP (control) groups. 45Ca2+ was delivered in microperfusate locally to ischaemic myocardium, with distribution and uptake assessed by 45Ca2+ recovery in microdialysate. Cardiomyocytes in vitro were exposed to a Ca2+ ionophore and tested for 45Ca2+ uptake. An accentuated myocardial calcium ion influx (observed as an increased microdialysate 45Ca2+ recovery in the extracellular milieu) was noted in control pigs compared with IP pigs during ischaemia. Suspended cardiomyocytes preincubated with a Ca2+ ionophore to increase the intracellular calcium ion pool and subsequently incubated with 45Ca2+, displayed lower 45Ca2+ uptake in cells compared with control cells not exposed to the ionophore, corroborating the idea of a strong relationship between degree of intracellular calcium overload and microdialysate 45Ca2+ recovery. The ischaemic insult was differentially verified by metabolic and injury markers. We introduce an in vivo method for serial assessment of myocardial calcium overload during ischaemia, using a MD technique and 45Ca2+ inclusion. IP leads to relatively less calcium overload as assessed by this new method, and we interpret this to mean that reduction in calcium overload is an important part of the IP protective effect.

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