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  • 1.
    Axelson, Hans W
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Human motor compensations for thixotropy-dependent changes in muscular resting tension after moderate joint movements2004In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 182, no 3, p. 295-304Article in journal (Refereed)
    Abstract [en]

    AIM:

    This study on healthy subjects explores history-dependent changes in the resting tension of relaxed wrist muscles after moderate joint excursions and the motor control consequences of these changes during voluntary wrist joint position maintenance.

    METHODS:

    Integrated surface electromyogram (IEMG) was recorded from wrist extensor/flexor muscles. Angular position and torque were recorded from the wrist joint. Changes in wrist flexor muscle resting tension were sensed by a force transducer pressed against the tendons.

    RESULTS:

    Consecutive stepwise changes (7.5 degrees ) in wrist joint position (within the dorsiflexed range) were either imposed on relaxed subjects or actively performed while the subjects under visual guidance tried to mimic the passive movements. In relaxed subjects, passive joint torque resistance at a given steady dorsiflexed position either gradually declined or rose depending on the direction of the previous transition movements. In corresponding voluntary contraction experiments, the IEMG amplitude from position holding wrist extensors was found to vary in a similar way as the passive torque resistance. Further, there was a strong correlation between history-dependent changes in extensor IEMG amplitude and stress alterations exhibited by the relaxed antagonist flexors. The above described, slowly subsiding post-movement mechanical and motor adaptations were accelerated by brief forceful cocontractions of the forearm muscles.

    CONCLUSION:

    Moderate stepwise changes in joint position are sufficient to induce history-dependent after-effects in passive muscular resting tension, after-effects which during voluntary position holding are effectively compensated for by the motor control system.

  • 2. Bergfors, M
    et al.
    Barnekow-Bergkvist, M
    Kalezic, N
    Lyskov, E
    Eriksson, Jan W
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology, Diabetes and Metabolism.
    Short-term effects of repetitive arm work and dynamic exercise on glucose metabolism and insulin sensitivity.2005In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 183, no 4, p. 345-56Article in journal (Refereed)
    Abstract [en]

    AIM: To determine whether repetitive arm work, with a large component of static muscle contraction alters glucose metabolism and insulin sensitivity.

    METHOD: Euglycemic clamps (2 h) were started in ten healthy individuals 15 min after 37 min periods of: (1) repetitive arm work in a simulated occupational setting; (2) dynamic concentric exercise on a cycle ergometer at 60% of VO(2max) and (3) a resting regime as a control. During the experimental periods, blood samples were collected, blood pressure was measured repeatedly and electrocardiogram (ECG) was recorded continuously. During the clamps, euglycemia was maintained at 5 mmol l(-1) and insulin was infused at 56 mU m(-2) min(-1) for 120 min.

    RESULTS: The insulin-mediated glucose disposal rate (M-value) for the steady-state period (60-120 min) of the clamp, tended to be lower following arm work than for both cycling and resting regimes. When dividing the steady-state period into 20-min intervals, the insulin sensitivity index (ISI) was significantly lower for arm work compared with the resting control situation between 60-80 min (P = 0.04) and 80-100 min (P = 0.01), respectively. Catecholamines increased significantly for arm work and cycling compared with resting regime. Data from heart rate variability (HRV) measurements indicated significant sympathetic activation during repetitive arm work.

    CONCLUSION: The results indicate that repetitive arm work might acutely promote insulin resistance, whereas no such effect on insulin resistance was produced by dynamic concentric exercise.

  • 3. Giorgino, F
    et al.
    Laviola, L
    Eriksson, Jan W
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology, Diabetes and Metabolism.
    Regional differences of insulin action in adipose tissue: insights from in vivo and in vitro studies.2005In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 183, no 1, p. 13-30Article in journal (Refereed)
    Abstract [en]

    Adipose tissue is now recognized to have a multitude of functions that are of importance in the regulation of energy balance and substrate metabolism. Different hormones, in particular insulin and catecholamines, govern the storage and utilization of energy in the triglyceride depots. In addition, adipocytes produce several different substances with endocrine or paracrine functions, which regulate the overall energetic homeostasis. With excess energy storage, obesity develops, leading to increased risk for type 2 diabetes and cardiovascular disease. The distribution of body fat appears to be even more important than the total amount of fat. Abdominal and, in particular, visceral adiposity is strongly linked to insulin resistance, type 2 diabetes, hypertension and dyslipidaemia, leading to increased risk of cardiovascular disease. The adverse metabolic impact of visceral fat has been attributed to distinct biological properties of adipocytes in this depot compared with other adipose tissue depots. Indeed, regional variations in the metabolic activity of fat cells have been observed. Furthermore, expression studies aiming at defining the unique biological properties of adipose tissues from distinct anatomical sites have identified depot-related differences in the protein content of fat-produced molecules. In this review we wish to summarize important results from the literature and also some recent data from our own work. The main scope is to describe the biological functions of adipose tissue, and to focus on metabolic, hormonal, and signalling differences between fat depots.

  • 4.
    Hansell, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrativ Fysiologi.
    Källskog, Örjan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrativ Fysiologi.
    Persson, A Erik G
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrativ Fysiologi.
    Introduction to the Fourth Acta Physiologica Scandinavica International Symposium on vasodilators in the development of hypertension: NO and dopamine2000In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 168, no 1, p. 19-19Article in journal (Other academic)
  • 5.
    Hansell, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrativ Fysiologi.
    Maric, C.
    Alcorn, D.
    Göransson, V.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Johnsson, C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Hällgren, Roger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Renomedullary interstitial cells regulate hyaluronan turnover depending on growth media osmolality suggesting a arole in renal water handling1999In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 165, no 1, p. 115-116Article in journal (Refereed)
  • 6.
    Henriksnäs, Johanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Phillipson, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Petersson, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Engstrand, L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Holm, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    An in vivo model for gastric physiological and pathophysiological studies in the mouse2005In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 184, no 2, p. 151-159Article in journal (Refereed)
    Abstract [en]

    Aim:  In vivo models for studying gastrointestinal physiology and pathophysiology are well established in rats. Since a number of genetically modified mice are available there is a need for reliable mouse models. The aim of this project was to develop an in vivo mouse model for gastrointestinal studies.

    Methods: C57bl/6, NMRI and transgenic FVB/N (expressing human α-1,3/4-fucosyltransferase) mice were anaesthetized with isoflurane and the gastric mucosa exteriorized for intravital microscopy. Acid–base status and acid secretion were measured and blood pressure was continuously monitored. Gastric mucosal blood flow was recorded by laser-Doppler flowmetry. Mucus thickness and accumulation rate were measured with micropipettes.

    Results: We have developed an in vivo mouse model for studies of the gastric mucosa. With isoflurane anaesthesia the preparation can be studied for up to 5 h with stable blood pressure and mucosal blood flow. Acid–base status agrees with results from other laboratories. Blood flow increased in both C57bl/6 and α1.3/4-FT mice in response to luminal HCl, and the mucus gel could be divided into a firmly and a loosely adherent layer, all comparable with results in the rat. However, the firmly adherent mucus layer was thinner (45 ± 2 μm), and the mucus accumulation rate lower, than in the rat. Furthermore, both basal and stimulated acid secretion showed lower outputs than in the rat.

    Conclusions: This model has great potential for investigations of gastrointestinal physiology and pathophysiology and can be applied for Helicobacter pylori infection studies.

  • 7. Holm, Lena
    et al.
    Flemström, G
    Nylander, O
    Duodenal alkaline secretion in rabbits: influence of artificial ventilation.1990In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 138, no 4, p. 471-8Article in journal (Refereed)
    Abstract [en]

    The effect of artificial ventilation on duodenal alkaline secretion and blood flow was studied in sodium pentobarbital-anaesthetized rabbits. A duodenal segment (approximately 3 cm) was cannulated in situ and continuously perfused with isotonic saline, and the bicarbonate secretion was titrated by pH-stat. Compared with the spontaneous breathing state, artificial ventilation improved the respiratory status of the animal, increasing Po2 and decreasing both Pco2 and plasma bicarbonate. Duodenal blood flow as measured with laser-Doppler flowmetry was not altered but the alkaline secretion was reduced. Pretreatment with the alpha 2-adrenoceptor antagonist yohimbine (0.5 mg kg-1 i.v., followed by 0.5 mg kg-1 h-1 i.v.) or the ganglionic blocker hexamethonium (10 mg kg-1 i.v.) did not affect the decline in duodenal alkaline secretion in response to artificial ventilation. Nor did these pretreatments affect the changes in plasma bicarbonate and Pco2 or significantly alter the blood flow. Increasing Pco2 in the respirator air increased the plasma Pco2 and bicarbonate concentration as well as the duodenal bicarbonate secretion. Pretreatment with the carbonic anhydrase inhibitor acetazolamide (80 mg kg-1 i.v.) reduced the bicarbonate secretion, and artificial ventilation induced a further reduction. Increasing Pco2 in the respirator in the animals pretreated with acetazolamide did not affect the bicarbonate secretion. Duodenal alkaline secretion was thus always reduced on artificial ventilation. The mechanism for this reduction does not seem to involve the sympathetic nervous system or the blood flow, but appears to be the consequence of alterations in the plasma concentration of bicarbonate and the plasma Pco2.

  • 8. Holm, Lena
    et al.
    Morsing, P
    Casellas, D
    Persson, A E
    Resetting of the pressure range for blood flow autoregulation in the rat kidney.1990In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 138, no 3, p. 395-401Article in journal (Refereed)
    Abstract [en]

    Both a myogenic response and the tubuloglomerular feedback control mechanism seem to be involved in autoregulation of glomerular filtration rate (GFR) and renal blood flow (RBF). Earlier experiments have shown that clamping of renal arterial perfusion pressure, below the autoregulatory range, reduces single-nephron GFR, and that this low value is maintained during the first 10-15 min after release of the clamp. It was also found that the tubuloglomerular feedback mechanism in the early declamp phase was strongly activated to reduce GFR. These findings can not be easily understood with the current knowledge of autoregulation, but would suggest a resetting of RBF and GFR autoregulation to a new level. To test this, left renal arterial perfusion pressure was reduced from 100 to 60 mmHg during 20 min with and without angiotensin converting enzyme inhibition (0.5 mg i.v. enalapril). Renal blood flow was measured with laser-Doppler flowmetry. When arterial perfusion pressure was reduced from 100 to 60 mmHg for 20 min, RBF was reduced to 77% of control and remained at this low level during the first minutes of declamp. In this situation there was an autoregulation to a new level. Renal blood flow was then slowly normalized (16.1 min). In the enalapril-treated animals RBF was only reduced to 85% during the 20 min of clamping and returned immediately to the control level at declamp. Thus, these experiments demonstrate that if renal blood flow is decreased by reducing the perfusion pressure below the normal autoregulatory range the pressure range for blood flow autoregulation resets to a lower level and that this change is mediated via the renin-angiotensin system.

  • 9.
    Holm-Rutili, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Physiology.
    Effects of prostaglandin E1, E2 and 16,16-dimethyl-E2 on gastric mucosal microcirculation and basal acid output in the rat1986In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 127, no 3, p. 313-321Article in journal (Refereed)
    Abstract [en]

    The effects of prostaglandins E1 (PGE1), E2 (PGE2) and 16,16-dimethyl-E2 (16,16-dm-PGE2) on the gastric mucosal microcirculation and (spontaneous) acid output were studied in anaesthetized rats. The superficial mucosal vessels were monitored on a TV screen using a microscope, TV camera and videorecorder for off-line analysis of red cell velocities (VRBC) and vessel diameters, from which the blood flow (QRBC) was calculated. The prostaglandins were either applied topically to the solution bathing the exposed mucosa or administered intravenously as a continuous infusion. Topical application of PGE1 (0.5 or 5 micrograms ml-1), PGE2 (5 or 50 micrograms ml-1) or 16,16-dm-PGE2 (0.005, 0.05 or 0.5 microgram ml-1) increased VRBC dose-dependently without altering acid output, except for the highest dose of PGE2 (50 micrograms ml-1) which inhibited acid output. The latter occurred in spite of a seven- to eight-fold increase in VRBC. Mucus secretion (evidenced by an impaired resolution of the TV image) also increased during topical application of the prostaglandins especially at higher doses. Intravenous PGE1, PGE2 (2.0 micrograms kg-1 min-1) or 16,16-dm-PGE2 (0.02 microgram kg-1 min-1) caused an initial and transient (5-10 min) fall in systemic arterial blood pressure and a decrease in VRBC and acid output. Intravenous 16,16-dm-PGE2 in a dose which did not affect secretion or systemic arterial blood pressure (0.002 microgram kg-1 min-1) still significantly reduced VRBC. Thus, topically applied PGE1, PGE2 or 16,16-dm-PGE2 dose-dependently increase VRBC while intravenous administration of the same prostaglandins reduce VRBC.

  • 10.
    Metry, George
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hall, C.
    Wikström, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Källskog, V.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Hansell, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Danielson, B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Fluid balance in patients with chronic renal failure assessed with N-terminal proatrial natriuretic peptide, atrial natriuretic peptide and ultrasonography2001In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 171, no 2, p. 117-122Article in journal (Refereed)
    Abstract [en]

    The N-terminal proatrial natriuretic peptide (proANP) has become an important parameter for assessing the prognosis of patients with cardiac disease. Its use for evaluating the hydration status in patients with chronic renal failure, however, is still under investigation. The present study comprised 12 haemodialysis (HD) and 17 pre-dialysis patients. In the HD patients, the inferior vena cava diameter during quiet expiration (IVCe) was estimated by ultrasonography and plasma concentrations of N-terminal proANP, atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate (cGMP) were measured before and 4 h after termination of HD. In the pre-dialysis patients venous blood samples were taken during rest to measure plasma N-terminal proANP and ANP and serum creatinine. Normal values for N-terminal proANP and ANP were obtained from 18 healthy volunteers. The plasma concentrations of N-terminal proANP and ANP in healthy volunteers were 328 +/- 92 and 11.4.0 +/- 3.1 pM L-1, respectively. In pre-dialysis patients, serum creatinine ranged from 110 to 447 microM L-1 and was significantly correlated to plasma N-terminal proANP (r = 0.60, P < 0.05) but not to ANP. This may indicate that N-terminal proANP is more dependent on renal function for its clearance than ANP, which is probably cleared by extrarenal mechanisms as well. In HD patients, IVCe was significantly correlated to the three hormones before HD, most strongly to N-terminal proANP. After dialysis, IVCe was significantly correlated to ANP and cGMP but was not correlated to N-terminal proANP. This may suggest that proANP takes a longer time than other hormones to reflect changes in intravascular volume. In conclusion, N-terminal proANP is a hormone closely related to degree of renal function. Furthermore, it is a sensitive marker reflecting the interdialytic hydration status in HD patients, as indicated by its high correlation to IVCe, a standard method which is used frequently nowadays to assess the body hydration. However N-terminal proANP could not reflect the acute changes in fluid volume induced by HD, probably because it is slowly metabolized.

  • 11.
    Metry, George
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Wikström, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Linde, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Danielson, Bo G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Gender and age differences in thoracic bioimpedance1997In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 161, no 2, p. 171-175Article in journal (Refereed)
    Abstract [en]

    Thoracic impedance consists of a constant baseline component Z0 and a time-variable component delta Z which represents the impedance change related to the cardiac cycle. The maximum part of delta Z [(dZ/dt)max] represents the peak of the ascending aortic blood flow. Measurements of basal thoracic impedance are affected by structural and anatomical differences in the thorax related to sex and ageing. This component is a variable in the denominator of Sramek's formula which is used for calculating stroke volume. The aim of this study was to elucidate the question as to whether the age- and sex-related variation in basal impedance may affect bioimpedance measurements of stroke volume. The study comprised 111 healthy subjects (55 males and 56 females) of ages between 20 and 69 years, divided according to age decades into five groups each of males and females. Stroke volume index (SI), Z0 and (dZ/dt)max were measured in every subject, using transthoracic bioimpedance cardiography. Z0 and (dZ/dt)max had significantly higher values in females than in males in every age group except the oldest one in the case of Z0 and the oldest two groups in the case of (dZ/dt)max. Stroke index showed no significant sex difference, although the higher Z0 in females may underestimate the values of stroke index. Elevation of (dZ/dt)max in females may therefore reflect a positive relation to Z0 rather than higher flow rates. Since Z0 and (dZ/dt)max are variants in opposite positions in Sramek's formula (denominator and numerator, respectively), this functional relationship may keep the bioimpedance measurements from being affected by the sex- and age-related changes in Z0.

  • 12. Morsing, P
    et al.
    Stenberg, A
    Casellas, D
    Mimran, A
    Müller-Suur, C
    Thorup, C
    Holm, Lena
    Persson, A E
    Renal interstitial pressure and tubuloglomerular feedback control in rats during infusion of atrial natriuretic peptide (ANP).1992In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 146, no 3, p. 393-8Article in journal (Refereed)
    Abstract [en]

    Atrial natriuretic peptide (ANP), injected at physiological concentrations, is known to induce both natriuresis and diuresis. It has been suggested by some investigators that these changes result from an increasing glomerular filtration rate (GFR), but others have been unable to demonstrate an increased GFR. The tubuloglomerular feedback (TGF) mechanism is an important regulator of GFR, and the sensitivity of TGF is decreased during ANP administration. Furthermore, resetting of TGF is, in most instances, related to changes in renal interstitial hydrostatic and oncotic pressures. It is also known that ANP may increase capillary permeability which may change renal interstitial pressure. The present study was performed to examine renal interstitial pressures and the TGF mechanism during ANP infusion. In accordance with previous studies, TGF sensitivity was found to be decreased. The tubular flow rate which elicited half the maximal drop in stop-flow pressure (Psf) was increased from 18.5 to 25.7 nl min-1. In contrast, ANP infusion resulted in a decreased interstitial hydrostatic pressure and an increased interstitial oncotic pressure. From previous experiments, such changes in interstitial pressures would be expected to increase TGF sensitivity. The changes in interstitial pressure cannot, therefore, directly explain the resetting of the feedback mechanism. In conclusion, the present paper shows a decreased renal net interstitial pressure after intravenous administration of ANP.

  • 13. Sababi, M
    et al.
    Holm, Lena
    Villus tip microcirculation in the rat duodenum.1995In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 154, no 2, p. 221-33Article in journal (Refereed)
    Abstract [en]

    Duodenal microvascular perfusion was measured in anaesthetized rats both as erythrocyte velocity (rcv) in capillaries in the tip of duodenal villi and by laser-Doppler flowmetry (LDF). Rcv increased transiently by about 40% during the first 5 min of luminal exposure to 10 mM (NaCl to isotonicity) hydrochloric acid, while LDF measurements only showed a transient increase of about 7%, followed by a prolonged reduction by about 11%. Since the LDF signal is a measure not only of villus microcirculation but also of blood flow in the deeper layers, our results may suggest that blood flow is transiently redistributed towards the villi from deeper layers. Hypovolaemia (bleeding by approximately 10% of the blood volume) reduced rcv in the capillaries by 63% during the first 5 min of hypotension, but reduced LDF only by about 12%, a discrepancy which suggests a shift in blood flow from the tip to deeper layers. The experiments were performed under atmospheric oxygen tension, but rcv in the villus capillaries exposed to abdominal PO2 (approximately 45 mmHg) did not differ significantly from the values obtained under the atmospheric oxygen condition, either in the resting situation or during hypotension. In conclusion, we have developed an animal model in which red cell velocity in the tip of the duodenal villi can be studied for several hours and in which alkaline secretion from the duodenum is similar to previously reported levels. Our results show that the villus tip microcirculation in the duodenum may respond differently from that of deeper layers of the duodenal wall.

  • 14.
    Sarabi, Mahziar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Fugmann, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Karlström, Brita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lithell, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    An ordinary mixed meal transiently impairs endothelium-dependent vasodilation in healthy subjects2001In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 172, no 2, p. 107-113Article in journal (Refereed)
    Abstract [en]

    This study was designed to evaluate the effects of an ordinary mixed meal on endothelium-dependent vasodilation. Ten young healthy volunteers were given a mixed meal (minced meat sauce with rice, 900 kcal, 34% of the energy content was fat). In the fasting state, at 60 and 120 min after the start of the meal, endothelium-dependent vasodilation and endothelium-independent vasodilation were evaluated by local infusion of metacholine (4 microg min (-1)) and sodium nitroprusside (10 microg min (-1)) in the brachial artery. Blood flow in the forearm was measured using venous occlusion plethysmography. Endothelium-dependent vasodilation decreased from 15.4 +/- 3.3 (mean +/- SD) at fasting to 13.7 +/- 3.5 mL min (-1) (100 mL tissue)-1 (P < 0.01) 60 min after feeding, but had returned to the fasting level at 120 min. At 60 min, but not in the fasting state, the serum level of free fatty acids was inversely related to endothelium-dependent vasodilation (r=-0.74, P < 0.05), although no significant net changes in FFA levels were seen. Endothelium-independent vasodilation was not affected by the mixed meal. No similar attenuations in endothelium-dependent vasodilation were seen during control meals. In conclusion, an ordinary mixed meal transiently attenuated endothelium-dependent vasodilation. Free fatty acids may be involved in this effect on endothelial function.

  • 15.
    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.
    Brodin, Lars-Åke
    Henriksen, Egil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Left ventricular volumes during exercise in endurance athletes assessed by contrast echocardiography2004In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 182, no 1, p. 45-51Article in journal (Refereed)
    Abstract [en]

    Aim:  The objective was to assess left ventricular (LV) volumes at rest and during upright submaximal exercise in endurance athletes to see whether changes in heart volume could explain the large predicted increase in cardiac output in endurance athletes.

    Method:  Contrast echocardiography was used to assess changes in LV volumes during upright bicycle exercise in 24 healthy male endurance athletes. Maximal oxygen uptake and oxygen pulse were measured by using cardiopulmonary exercise testing.

    Results:  From rest to exercise at a heart rate of 160 beats min−1 end-diastolic volume increased by 18% (P < 0.001) and end-systolic volume decreased by 21% (P = 0.002). Stroke volume showed an almost linear increase during exercise (45% increase, P < 0.001). The increase in end-diastolic volume contributed to 73% of the increase in stroke volume. No significant differences were observed between stroke volume calculated from LV volumes with contrast echocardiography and stroke volume calculated from oxygen pulse at heart rates of 130 and 160 beats min−1. Using the linear regression equation between oxygen uptake and cardiac output assessed by echocardiography during exercise (r = 0.87, P = 0.002), cardiac output at maximal exercise was estimated at 33 ± 3 L min−1, with an estimated increase in stroke volume by 69% from rest to maximal exercise.

    Conclusion:  By using contrast echocardiography, a large increase in stroke volume in endurance athletes could be explained by an almost linear increase in end-diastolic volume and an initial small decrease in end-systolic volume during incremental upright exercise.

  • 16.
    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.
    Jonason, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Ahrén, Tom
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Damm, Sabine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Wesslén, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Henriksen, Egil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Left ventricular volume changes during supine exercise in young endurance athletes2003In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 177, no 4, p. 467-472Article in journal (Refereed)
    Abstract [en]

    Aim:  The primary objective of the study was to measure the relative left ventricular volumes and the changes in left ventricular ejection fraction during supine position from rest to exercise in young endurance athletes. The secondary objective was to examine if there were gender differences regarding the volume reply and ejection fraction with exercise.

    Method:  Sixty-five (35 female and 30 males) young healthy Swedish orienteers participated in the study. Left ventricular volume and ejection fraction changes between rest and submaximal supine bicycle exercise were measured with radionuclide ventriculography.

    Results:  The mean left ventricular end-diastolic volume increased by 13% (P < 0.001) but there was no change in end-systolic volume. Stroke volume was found to increase by 21% (P < 0.001). Left ventricular ejection fraction increased significantly (>0.04 units) in 54% of the athletes from rest to exercise; 5% of the athletes showed a decrease in ejection fraction. A negative correlation was found between ejection fraction at rest and the difference in ejection fraction from rest to exercise (r = −0.38, P = 0.002). There were no gender differences in the left ventricular volume changes or ejection fraction.

    Conclusion:  During submaximal supine exercise, the adjustments in cardiac volumes in endurance athletes were small. There were no gender disparities concerning the left ventricular volume reply during exercise.

  • 17. Synnerstad, I
    et al.
    Persson, A E
    Holm, Lena
    Effect of inhibition of pentagastrin-stimulated acid secretion on gastric mucosal gland luminal pressure.1997In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 160, no 1, p. 103-11Article in journal (Refereed)
    Abstract [en]

    We demonstrated previously that hydrochloric acid secreted from the gastric glands traverses the mucus layer in channels above the gland openings. The driving force for creation of these channels is most probably the hydrostatic pressure generated in the gastric gland lumen during stimulation of acid secretion. Here we investigated the effect of total inhibition of acid secretion on gland luminal pressure. Glandular pressure was measured in vivo with a pressure-sensitive microelectrode technique in Inactin-anaesthetized Sprague Dawley or Lewis x DA F1 rats. Glandular pressure was significantly reduced after ranitidine inhibition of acid secretion, from 17.2 +/- 2.1 mmHg during pentagastrin stimulation to 11.2 +/- 1.2 mmHg. This was also true when pentagastrin infusion was continued after inhibition of secretion with ranitidine. Omeprazole, however, did not significantly alter gland luminal pressure although it totally inhibited acid secretion. With continuation of pentagastrin infusion after omeprazole inhibition, glandular pressure increased significantly from 17.6 +/- 3.4 to 20.1 +/- 3.3 mmHg. In conclusion, total inhibition of acid secretion with ranitidine reduces but does not abolish gland luminal pressure. After omeprazole inhibition of acid secretion the gastric gland luminal pressure persisted or even increased. Since the volume secretion is lower after omeprazole administration than during pentagastrin stimulation, the outflow resistance most probably had increased after omeprazole injection. Suggestions for increased outflow resistance are narrowing in the upper part of the gland lumen by conformational changes of the cells or muscle contractions, and/or an increase in mucus secretion or viscosity.

  • 18. Tähepõld, P
    et al.
    Elfström, P
    Eha, I
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Kals, J
    Taal, G
    Talonpoika, A
    Valen, G
    Vaage, J
    Starkopf, J
    Exposure of rats to hyperoxia enhances relaxation of isolated aortic rings and reduces infarct size of isolated hearts.2002In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 175, no 4, p. 271-7Article in journal (Refereed)
    Abstract [en]

    Exposure of rats to hyperoxia before organ harvesting protected their isolated hearts against global ischaemia-reperfusion injury in a previous study. The present study investigates whether hyperoxia influences vasomotor function and regional ischaemia of the heart. Isolated rings of the thoracic aorta were obtained from rats immediately or 24 h after in vivo exposure to 60 min of hyperoxia (>95% O2), and the in vitro dose-response to phenylephrine (PHE), prostaglandin F2alpha (PGF2alpha) and endothelin-1 (ET-1), acetylcholine (Ach) and sodium nitroprusside (SNP) was assessed. Hyperoxia in vivo increased the relaxation of aortic rings to Ach and SNP, while it delayed contraction to PHE. The effect was more evident when the vessels were harvested immediately rather than 24 h after hyperoxic exposure. In separate experiments rat hearts were isolated immediately after hyperoxia, buffer-perfused, and subjected to 30 min of regional ischaemia and reperfused for 120 min. Infarct size was determined by triphenyl tetrazolium chloride staining. Hyperoxia significantly reduced infarct size. In normoxic controls 23.0 +/- 8.3% of the area at risk was infarcted, while in hyperoxic animals infarct size was 14.8 +/- 5.6% of the area at risk (P = 0.012). Exposure of rats to hyperoxia modifies the vasomotor response of isolated aortic rings, and reduces the infarct size of isolated rat heart. These novel aspects of hyperoxic treatment require further studies to explore the potential of its clinical application.

  • 19.
    Zemgulis, Vitas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Ronquist, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Bjerner, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Henze, Axel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Waldenström, Anders
    Thelin, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Energy-related metabolites during and after induced myocardial infarction with special emphasis on the reperfusion injury after extracorporeal circulation2001In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 171, no 2, p. 129-143Article in journal (Refereed)
    Abstract [en]

    In the clinical setting great efforts have been made with contradictory results to operate upon acutely myocardial ischaemic patients. The reasons for the absence of clear-cut results are not well understood nor are they scientifically explored. To resolve this problem further, we attempted to design an experimental in vivo model to mimic acute myocardial ischaemia followed by extracorporeal circulation (ECC) and reperfusion. One of the main targets of our protocol was monitoring of myocardial energy metabolism by microdialysis (MCD) during the periods of coronary occlusion (60 min), hypothermic (30 degrees C) ECC and cardioplegia (45 min), followed by reperfusion with (30 min) and without (60 min) ECC. In eight anaesthetized, open-chest pigs, myocardial lactate, pyruvate, adenosine, taurine, inosine, hypoxanthine and guanosine were sampled with MCD in both ischaemic and non-ischaemic areas. Myocardial area at risk and infarct size were quantified with the modified topographical evaluation methods. The principal finding with this experimental setup was a biphasic release pattern of lactate, adenosine, taurine, inosine, hypoxanthine and guanosine from ischaemic myocardium. Lactate levels were equally high in reperfused ischaemic and non-ischaemic myocardial tissue. Pyruvate demonstrated consistently higher values in non-ischaemic myocardium throughout the experiment. A pattern was discernible, lactate being a marker of compromised cell energy metabolism, and taurine being a marker of disturbed cell integrity. Of special interest was the increased level of pyruvate in microdialysates of non-ischaemic myocardium as compared with its ischaemic counterpart. In conclusion, we found disturbances in energy metabolism and cell integrity not only in ischaemic but also in non-ischaemic tissue during reperfusion implying that non-ischaemic myocardium demonstrated an unexpected accumulation of lactate and pyruvate. These new findings could at least partly be explicatory to the increased risk of heart surgery in connection with acute myocardial infarction.

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