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  • 51.
    Salehpour, Mehran
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Tillämpad kärnfysik.
    Håkansson, Karl
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Tillämpad kärnfysik.
    Westermark, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Antoni, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för nuklearmedicin och PET.
    Wikström, Gerhard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Possnert, Possnert
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Tillämpad kärnfysik.
    Life science applications utilizing radiocarbon tracing2013Inngår i: Radiocarbon, ISSN 0033-8222, E-ISSN 1945-5755, Vol. 55, nr 2-3, s. 865-873Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Radiocarbon-based accelerator mass spectrometry (AMS) facilities at Uppsala University include a measurement center for archaeological applications and a separate entity dedicated to life science research. This paper addresses the latter, with the intention of giving a brief description of the biomedical activities at our laboratory, as well as presenting new data. The ultra-small sample preparation method, which can be used down to a few μg C samples, is outlined and complemented with new results. Furthermore, it is shown that the average secondary ion current performance for small samples can be improved by increasing the distance between the cathode surface and the pressed graphite surface. Finally, data is presented for a new application: Amyloidoses are a group of diseases where the conformational changes in specific proteins’ structure lead to the formation of extracellular deposits that spread and increase in mass and eventually may lead to total organ failure and death. The formation timeframe is unknown and yet it is an important clue for the elucidation of the mechanism. We present results on bomb-peak dating of 4 different types of purified amyloid proteins from human postmortem heart and spleen samples. The data indicates that the average measured age of the carbon originating from the systemic amyloid types studied here correspond to a few years before the death of the subject. This suggests that a major part of the fibril formation takes place during the last few years before death, rather than as an accumulation of amyloid deposits over decades.

  • 52.
    Sandqvist, Anna
    et al.
    Umea Univ, Div Clin Pharmacol, Dept Pharmacol & Clin Neurosci, Umea, Sweden..
    Henrohn, Dan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Egeröd, Hanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Hedeland, Mikael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för analytisk farmaceutisk kemi. Natl Vet Inst SVA, Dept Chem, Uppsala, Sweden..
    Wernroth, Lisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Bondesson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för analytisk farmaceutisk kemi. Natl Vet Inst SVA, Dept Chem, Uppsala, Sweden..
    Schneede, Jorn
    Umea Univ, Div Clin Pharmacol, Dept Pharmacol & Clin Neurosci, Umea, Sweden..
    Wikström, Gerhard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Acute vasodilator response to vardenafil and clinical outcome in patients with pulmonary hypertension2015Inngår i: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 71, nr 10, s. 1165-1173Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose Acute vasodilator testing is recommended in patients with pulmonary arterial hypertension to identify individuals who may benefit from long-term treatment with oral calcium channel blockers. The aim of this study was to investigate the use of vardenafil in acute vasoreactivity testing compared to adenosine. Methods A total of 20 patients eligible for right heart catheterisation were enrolled. Acute vasoreactivity testing was carried out with intravenous (iv) adenosine (n = 18) followed by oral vardenafil (n = 20). Haemodynamic responses were recorded at baseline and after 60 min (vardenafil). Responders were defined according to consensus guideline criteria. Results Both vardenafil and adenosine significantly decreased mean pulmonary arterial pressure (mPAP, p < 0.001 and p = 0.026, respectively) and pulmonary vascular resistance (p < 0.001 and p > 0.001, respectively), and significantly increased cardiac output (p = 0.001 and p = 0.005, respectively). Vardenafil reduced mPAP more than adenosine (p = 0.044), while adenosine resulted in higher responses of cardiac index (p = 0.009) and pulmonary arterial oxygen saturation (p = 0.042). Acute adverse reactions were common with adenosine, while no side effects were observed after a single oral dose vardenafil. Vardenafil identified five responders (out of 20), while adenosine identified three responders (out of 18). During a 7-year follow-up, vardenafil responders had significantly lower NT-proBNP levels compared to non-responders. Conclusions Vardenafil may be safely used for acute vasoreactivity testing in patients with PH. A single oral dose of vardenafil is better tolerated than iv adenosine and may identify additional responders who could benefit from long-term vasodilator treatment.

  • 53.
    Sandqvist, Anna
    et al.
    Umea Univ, Clin Pharmacol, Dept Pharmacol & Clin Neurosci, S-90187 Umea, Sweden..
    Schneede, Jörn
    Umea Univ, Clin Pharmacol, Dept Pharmacol & Clin Neurosci, S-90187 Umea, Sweden..
    Kylhammar, David
    Lund Univ, Dept Clin Sci Lund, Cardiol, Lund, Sweden.;Skane Univ Hosp, Sect Heart Failure & Valvular Dis, Lund, Sweden..
    Henrohn, D
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Lundgren, Jakob
    Lund Univ, Dept Clin Sci Lund, Cardiol, Lund, Sweden.;Skane Univ Hosp, Sect Heart Failure & Valvular Dis, Lund, Sweden..
    Hedeland, Mikael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Analytisk vetenskap. Natl Vet Inst SVA, Dept Chem, Uppsala, Sweden..
    Bondesson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Analytisk vetenskap. Natl Vet Inst SVA, Dept Chem, Uppsala, Sweden..
    Rådegran, Göran
    Lund Univ, Dept Clin Sci Lund, Cardiol, Lund, Sweden.;Skane Univ Hosp, Sect Heart Failure & Valvular Dis, Lund, Sweden..
    Wikström, Gerhard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala Univ, Dept Med Sci, Cardiol, Uppsala, Sweden..
    Plasma l-arginine levels distinguish pulmonary arterial hypertension from left ventricular systolic dysfunction2018Inngår i: Heart and Vessels, ISSN 0910-8327, E-ISSN 1615-2573, Vol. 33, nr 3, s. 255-263Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Pulmonary arterial hypertension (PAH) is a life-threatening condition, characterized by an imbalance of vasoactive substances and remodeling of pulmonary vasculature. Nitric oxide, formed from l-arginine, is essential for homeostasis and smooth muscle cell relaxation in PAH. Our aim was to compare plasma concentrations of l-arginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) in PAH compared to left ventricular systolic dysfunction (LVSD) and healthy subjects. This was an observational, multicenter study comparing 21 patients with PAH to 14 patients with LVSD and 27 healthy subjects. Physical examinations were obtained and blood samples were collected. Plasma levels of ADMA, SDMA, l-arginine, l-ornithine, and l-citrulline were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Plasma levels of ADMA and SDMA were higher, whereas l-arginine and l-arginine/ADMA ratio were lower in PAH patients compared to healthy subjects (p < 0.001). Patients with PAH also had lower levels of l-arginine than patients with LVSD (p < 0.05). l-Arginine correlated to 6 min walking distance (6MWD) (r (s) = 0.58, p = 0.006) and l-arginine/ADMA correlated to WHO functional class (r (s) = -0.46, p = 0.043) in PAH. In conclusion, l-arginine levels were significantly lower in treatment na < ve PAH patients compared to patients with LVSD. Furthermore, l-arginine correlated with 6MWD in PAH. l-arginine may provide useful information in differentiating PAH from LVSD.

  • 54. Sartipy, Ulrik
    et al.
    Kjellman, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Samuelsson, Sten
    Hagerman, Inger
    Wikström, Gerhard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Larsson, Thomas
    Albåge, Anders
    Lindblom, Dan
    Left ventricular reconstruction as an alternative to heart transplantation: a case report2006Inngår i: Heart Surgery Forum, ISSN 1098-3511, E-ISSN 1522-6662, Vol. 9, nr 3, s. E638-E640Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A 57-year-old man with dilated cardiomyopathy was referred to our institution to be assessed for heart transplantation. He had symptoms of severe heart failure and left ventricular dysfunction. We proposed surgical ventricular restoration (the Dor procedure) as an alternative to heart transplantation. The patient underwent successful surgery and an uneventful postoperative course. Pre- and postoperative investigations are presented. One year after surgery, the patient is in good clinical and functional condition. This case illustrates that surgical ventricular restoration can be an alternative to heart transplantation.

  • 55. Selimovic, N.
    et al.
    Lövgren Ekmehag, B.
    Jansson, K.
    Larsen, F.
    Söderberg, S.
    Wikström, Gerhard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Pulmonary Arterial Hypertension in Sweden: First Data from a National Registry2012Inngår i: The Journal of Heart and Lung Transplantation, ISSN 1053-2498, E-ISSN 1557-3117, Vol. 31, nr 4, s. S284-S284Artikkel i tidsskrift (Annet vitenskapelig)
  • 56.
    Stålhammar, Jan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Boman, K.
    Umea Univ, Res Unit, Skelleftea Cty Hosp, Med & Geriatr,Dept Publ Hlth, Umea, Sweden..
    Olofsson, M.
    Umea Univ, Res Unit, Skelleftea Cty Hosp, Med & Geriatr,Dept Publ Hlth, Umea, Sweden..
    Lindmark, K.
    Umea Univ, Ctr Heart, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Lahoz, R.
    Novartis Pharma AG, Basel, Switzerland..
    Corda, S.
    Novartis Pharma AG, Basel, Switzerland..
    Wintzell, V.
    IMS Hlth Sweden, Stockholm, Sweden..
    Linder, R.
    IMS Hlth Sweden, Stockholm, Sweden..
    Gondos, A.
    IMS Hlth Germany, Berlin, Germany..
    Wikström, Gerhard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    A description of unselected patients with heart failure: a swedish population-based study2016Inngår i: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 18, s. 195-195Artikkel i tidsskrift (Annet vitenskapelig)
  • 57.
    Stålhammar, Jan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Boman, K.
    Umea Univ, Res Unit, Med & Geriatr, Skelleftea Cty Hosp,Dept Publ Hlth, Umea, Sweden..
    Olofsson, M.
    Umea Univ, Res Unit, Med & Geriatr, Skelleftea Cty Hosp,Dept Publ Hlth, Umea, Sweden..
    Lindmark, K.
    Umea Univ, Dept Publ Hlth & Clin Med, Ctr Heart, Umea, Sweden..
    Lahoz, R.
    Novartis Pharma AG, Basel, Switzerland..
    Corda, S.
    Novartis Pharma AG, Basel, Switzerland..
    Wintzell, V.
    IMS Hlth Sweden, Stockholm, Sweden..
    Linder, R.
    IMS Hlth Sweden, Stockholm, Sweden..
    Gondos, A.
    IMS Hlth Germany, Berlin, Germany..
    Wikström, Gerhard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Recent trends in diagnostic work-up among unselected patients newly diagnosed with heart failure: a Swedish population-based study2016Inngår i: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 18, s. 54-55Artikkel i tidsskrift (Annet vitenskapelig)
  • 58.
    Stålhammar, Jan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Boman, K.
    Umea Univ, Dept Publ Hlth & Clin Med, Res Unit, Med, Umea, Sweden..
    Olofsson, M.
    Umea Univ, Dept Publ Hlth & Clin Med, Res Unit, Med, Umea, Sweden..
    Wikström, Gerhard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Bergman, G. J.
    QuintilesIMS, Solna, Sweden..
    Tornblom, M.
    QuintilesIMS, Solna, Sweden..
    Wintzell, V.
    QuintilesIMS, Solna, Sweden..
    Wirta, S. Bruce
    Novartis Sweden AB, Stockholm, Sweden..
    Proenca, C. C.
    Wellmera AG, Basel, Switzerland..
    Schlienger, R.
    Novartis Pharma AG, Basel, Switzerland..
    Lindmark, K.
    Umea Univ, Dept Publ Hlth & Clin Med, Ctr Heart, Umea, Sweden..
    Management of patients with heart failure with preserved versus reduced ejection fraction: a retrospective population-based cohort study in Sweden2017Inngår i: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 19, s. 54-55Artikkel i tidsskrift (Annet vitenskapelig)
  • 59.
    Stålhammar, Jan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Stern, Lee
    Linder, Ragnar
    Sherman, Steve
    Parikh, Rohan
    Ariely, Rinat
    Deschaseaux, Celine
    Wikström, Gerhard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    The burden of preserved ejection fraction heart failure in a real-world Swedish patient population2014Inngår i: Journal of Medical Economics, ISSN 1369-6998, E-ISSN 1941-837X, Vol. 17, nr 1, s. 43-51Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: To evaluate resource use and associated costs in patients with a diagnosis of heart failure with preserved ejection fraction (HF-PEF) in Sweden.

    METHODS: This retrospective study identified real-world patients with an ICD-10 diagnosis code for heart failure (I50) for the period between July 1, 2005 and December 31, 2006 from electronic medical records of primary care centers in Uppsala County Council, and in the Swedish patient registry data. Patients were categorized as having HF-PEF (left ventricle ejection fraction [LVEF] > 50%) during the index period. The study assessed medication utilization, outpatient visits, hospitalizations, and associated healthcare costs, as well as the incidence rates and time to all-cause and heart failure mortality following the index period.

    RESULTS: The study included 137 HF-PEF patients with a mean age of 77.1 (SD = 9.1) years. Over 50% of HF-PEF patients were female and hypertensive. Nearly all patients received ≥ 1 medication post-index. Patients had an average of 1.5 heart failure related hospitalizations per follow-up year. The average annual per patient cost for the management of a HF-PEF patient was found in Sweden to be Swedish Krona (SEK) 108,246 (EURO [EUR] 11,344). Hospitalizations contributed to more than 80% of the total cost. All-cause mortality over the 18-month study period was 25.5%, and more than 50% of these deaths occurred within 1 year of index.

    LIMITATIONS: Due to the limitations of registry data, it is not possible to confirm the HF diagnosis, and therefore the accuracy of registry records must be assumed. Other factors such as short follow-up time, the study-mandated LVEF assessment, and a lack of drug duration data may also have an impact on the study results.

    CONCLUSIONS: All-cause mortality was high in the HF-PEF population, with more than half of patients dying within 1 year of study follow-up. Study results also indicate that 60% of HF-PEF patients have ≥ 1 hospitalization during follow-up. Hospitalizations, especially heart failure related admissions, represent a substantial proportion of the total healthcare burden of patients with HF-PEF in Sweden.

  • 60.
    Stålhammar, Jan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Stern, Lee
    Linder, Ragnar
    Sherman, Steven
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Parikh, Rohan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Ariely, Rinat
    Wikström, Gerhard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Resource utilization and cost of heart failure associated with reduced ejection fraction in Swedish patients2012Inngår i: Journal of medical economics, ISSN 1941-837X, Vol. 15, nr 5, s. 938-946Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIM:

    The purpose of this study was to assess healthcare utilization and costs for heart failure patients with reduced ejection fraction (HF-REF) in Sweden.

    METHODS AND RESULTS:

    This was a retrospective, population-based cohort study of patients diagnosed with HF-REF during a period of 18 months at 31 primary care centers in Uppsala County, Sweden. Data was obtained from computerized records from these centers, the Swedish Patient Registry, the Swedish Prescription Registry, the Cause of Death Registry, and a local echocardiography registry maintained by the Department of Physiology, Uppsala University Hospital. Main outcome measures were cardiovascular and heart-failure-related hospitalizations, outpatient visits, medication utilization, mortality (all-cause, cardiovascular, and heart-failure), and healthcare costs for HF-REF patients. During the index period, 252 heart failure patients had a left ventricular ejection fraction measurement ≤ 40% and were categorized as having HF-REF. More than half of the patients had ≥ 1 cardiovascular or heart failure-related hospitalization. On average, patients had >2 such hospitalizations annually. They also averaged ∼1 cardiovascular or heart-failure-related outpatient visit per year. All-cause mortality was high: 15.9% patients died within 1 year after the index date. The mean annual cost per patient for heart-failure-related hospitalizations was SEK 72,613 (EUR 7610). In contrast, annual prescription costs were low, on average 3% of total cost (SEK 3503, EUR 367 per patient)

    LIMITATIONS:

    The main limitations of this study include a short follow-up time and small sample size. Also, certain data were missing, such as echocardiograms (available for only 28% of patients), and information on patients' New York Heart Association (NYHA) functional class, validity period for prescriptions or the units of medication prescribed, and medication dosing. Furthermore, the overall mortality could have been under-estimated, as only the primary cause of death was included in the analysis.

    CONCLUSIONS:

    The main burden associated with HF-REF is related to hospitalizations for heart-failure events. Effective treatment options that decrease hospitalization rates could reduce patients' suffering and potentially offer considerable cost savings.

  • 61. Söderberg, Stefan
    et al.
    Carlberg, Bo
    Ekmehag, Björn
    Jansson, Kjell
    Larsen, Flemming
    Lockowandt, Ulf
    Nisell, Magnus
    Selimovic, Nedim
    Ullman, Bengt
    Wall, Kent
    Wikström, Gerhard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Genmäle om begäran om lungskintigrafi: En akademisk studie som vi tror kan förändra vården av kronisk lungemboli: [A reply on requesting pulmonary scintigraphy. An academic study we believe can change the care of chronic pulmonary embolism].2011Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 108, nr 24-25, s. 1316-1317; discussion 1318Artikkel i tidsskrift (Fagfellevurdert)
  • 62.
    Sörensen, Jens
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för nuklearmedicin och PET.
    Ståhle, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Thoraxkirurgi.
    Långström, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för nuklearmedicin och PET.
    Frostfeldt, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Wikström, Gerhard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Hedenstierna, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Simple and accurate assessment of forward cardiac output by use of 1-[11C]acetate PET verified in a pig model2003Inngår i: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 44, nr 7, s. 1176-1183Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Dynamic 1-(11)C-acetate PET (AC-PET) allows quantification of myocardial blood flow and oxidative metabolism. We wanted to determine the accuracy of AC-PET in measuring cardiac output (CO) using first-pass analysis and the indicator dilution principle. Further, we wanted to investigate the pulmonary uptake of acetate in relation to left atrial filling pressures and ventricular function.

    METHODS: Twenty-four steady-state experiments were performed in 5 domestic pigs. Pulmonary capillary wedge pressure (PCWP) and CO by thermodilution (CO(thermo)) were recorded invasively simultaneous with AC-PET scans at baseline (n = 9), dobutamine infusion (n = 6), high-dose metoprolol and morphine (n = 6), and angiotensinamide infusion (n = 3). 1-(11)C-Acetate was injected as a rapid manual bolus. Regions of interest (ROIs) were placed in the right (RV) and left (LV) heart cavities. Time-activity curves were constructed and the area under the curve (AUC) was integrated from beginning the scan to the time of visually determined recirculation by simple arithmetic. CO by PET (CO(PET)) was calculated as injected dose/AUC. Image handling and curve analysis were repeated by a blinded observer. Total pulmonary extravascular retention of (11)C, expressed as percentage of injected dose (lung-uptake %ID), was measured using a combination of transmission, (15)O-carbon monoxide, and AC-PET scans.

    RESULTS: CO(thermo) ranged from 2.1 to 8.2 L/min. CO(PET) determined from both LV and RV was linearly related to CO(thermo) with slopes close to 1 (LV, r = 0.98; RV, r = 0.96; both P < 0.001). Interobserver reproducibility was r = 0.98, P < 0.001. The PCWP range was 6-14 mm Hg and the lung-uptake %ID was 2.7-8.5 %ID. When normalized to baseline, lung-uptake %ID was correlated with PCWP (r = 0.56, P = 0.01) and linearly correlated with LV input resistance (PCWP divided by CO(thermo); r = 0.91, P < 0.001). When both lung-uptake %ID and stroke volume were normalized to baseline, a piecewise linear relation was found (r = 0.95, P < 0.001).

    CONCLUSION: Our results suggest that measurements of CO by AC-PET are feasible and accurate. Using RV ROIs might favor CO measurements by any injectable PET tracer. The lung-uptake %ID might be useful in evaluation of pulmonary congestion, but further studies are needed.

  • 63. Waldenström, Anders
    et al.
    Haney, M.
    Biber, B.
    Kavianipour, Mohammad
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Moritz, T.
    Strandén, P.
    Wikström, Gerhard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Ronquist, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Ischaemic preconditioning is related to decreasing levels of extracellular adenosine that may be metabolically useful in the at-risk myocardium: an experimental study in the pig2010Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 199, nr 1, s. 1-9Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim: 'Pre-treatment' with short repetitive periods of ischaemia (ischaemic preconditioning) has proved to be a powerful mechanism for modification of the extent of myocardial damage following acute coronary artery occlusion. The exact mechanism of protection induced by ischaemic preconditioning is not known. We herewith put forward a contributing component for protection with preconditioning involving a shift in the adenylate kinase (AK) equilibrium reaction in favour of adenosine triphosphate (ATP) formation. Methods: A coronary artery was occluded in anaesthetized thoracotomized pigs to induce ischaemic preconditioning as well as a longer period of ischaemia. Microdialysis probes were inserted in ischaemic and control myocardium and were infused with (14)C- adenosine with two different specific activities. (14)C-lactate was identified and measured in the effluent. Results: (14)C-adenosine was taken up by non-preconditioned and preconditioned myocardium during ischaemia. Significantly increased levels of (14)C-lactate were recovered in preconditioned myocardium. (14)C-adenosine with high specific activity resulted in a specific activity of lactate that was 2.7 times higher than that of lactate after administration of (14)C-adenosine with low specific activity. Mass spectrography verified the identity of (14)C-lactate. Conclusions: Preconditioning up-regulates a new metabolic pathway (starting with 5'-nucleotidase and ending up with lactate) resulting in ATP formation in the micromolar range on top of another effect terminating in a useful shift in the AK equilibrium reaction in favour of ATP generation in the millimolar range. Although the up-regulation of the purine nucleoside phosphorylase pathway is clearly demonstrated, its biological relevance remains to be proved.

  • 64.
    Wikström, Bernt Gerhard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Correspondence concerning the article: Is levosimendan better than dobutamine in acute heart failure in patients on beta blockade treatment? What is the evidence?2010Inngår i: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 12, nr 8, s. 893-893Artikkel i tidsskrift (Fagfellevurdert)
  • 65.
    Wikström, G
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Kavianipour, M
    Ronquist, G
    Waldenström, A
    Pre-conditioning activates adenosine utilization in a cost-effective way during myocardial ischaemia.2001Inngår i: Acta Physiol Scand, ISSN 0001-6772, Vol. 173, nr 2, s. 185-94Artikkel i tidsskrift (Annet vitenskapelig)
  • 66.
    Wikström, Gerhard
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Blomström-Lundqvist, Carina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin.
    Andrén, Bertil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin.
    Lönnerholm, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin.
    Blomström, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin.
    Freemantle, Nick
    Remp, Thomas
    Cleland, John G. F.
    The effects of aetiology on outcome in patients treated with cardiac resynchronization therapy in the CARE-HF trial2009Inngår i: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 30, nr 7, s. 782-788Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIMS: Cardiac dyssynchrony is common in patients with heart failure, whether or not they have ischaemic heart disease (IHD). The effect of the underlying cause of cardiac dysfunction on the response to cardiac resynchronization therapy (CRT) is unknown. This issue was addressed using data from the CARE-HF trial. METHODS AND RESULTS: Patients (n = 813) were grouped by heart failure aetiology (IHD n = 339 vs. non-IHD n = 473), and the primary composite (all-cause mortality or unplanned hospitalization for a major cardiovascular event) and principal secondary (all-cause mortality) endpoints analysed. Heart failure severity and the degree of dyssynchrony were compared between the groups by analysing baseline clinical and echocardiographic variables. Patients with IHD were more likely to be in NYHA class IV (7.5 vs. 4.0%; P = 0.03) and to have higher NT-proBNP levels (2182 vs. 1725 pg/L), indicating more advanced heart failure. The degree of dyssynchrony was more pronounced in patients without IHD (assessed using mean QRS duration, interventricular mechanical delay, and aorta-pulmonary pre-ejection time). Left ventricular ejection fraction and left ventricular end-systolic volume improved to a lesser extent in the IHD group (4.53 vs. 8.50% and -35.68 vs. -58.52 cm(3)). Despite these differences, CRT improved all-cause mortality, NYHA class, and hospitalization rates to a similar extent in patients with or without IHD. CONCLUSION: The benefits of CRT in patients with or without IHD were similar in relative terms in the CARE-HF study but as patients with IHD had a worse prognosis, the benefit in absolute terms may be greater.

  • 67.
    Wikström, Gerhard
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Boman, K.
    Umea Univ, Skelleftea Cty Hosp, Dept Publ Hlth, Res Unit,Med & Geriatr, Umea, Sweden..
    Olofsson, M.
    Umea Univ, Skelleftea Cty Hosp, Dept Publ Hlth, Res Unit,Med & Geriatr, Umea, Sweden..
    Lindmark, K.
    Umea Univ, Dept Publ Hlth & Clin Med, Ctr Heart, Umea, Sweden..
    Lahoz, R.
    Novartis Pharma AG, Basel, Switzerland..
    Corda, S.
    Novartis Pharma AG, Basel, Switzerland..
    Wintzell, V.
    IMS Hlth Sweden, Stockholm, Sweden..
    Linder, R.
    IMS Hlth Sweden, Stockholm, Sweden..
    Gondos, A.
    IMS Hlth Germany, Berlin, Germany..
    Stålhammar, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Dosing of heart failure treatments in newly diagnosed unselected patients in sweden: compliance with european society of cardiology guidelines2016Inngår i: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 18, s. 341-341Artikkel i tidsskrift (Annet vitenskapelig)
  • 68.
    Wikström, Gerhard
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala Univ, Inst Med Sci, Uppsala, Sweden..
    Boman, K.
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Olofsson, M.
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Lindmark, K.
    Umea Univ, Ctr Heart, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Lahoz, R.
    Novartis Pharma AG, Basel, Switzerland..
    Corda, S.
    Novartis Pharma AG, Basel, Switzerland..
    Wintzell, V.
    IMS Hlth Sweden, Stockholm, Sweden..
    Linder, R.
    IMS Hlth Sweden, Stockholm, Sweden..
    Gondos, A.
    IMS Hlth Germany, Berlin, Germany..
    Stålhammar, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Exposure to heart failure treatments in newly diagnosed patients in Sweden2016Inngår i: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 18, s. 48-48Artikkel i tidsskrift (Annet vitenskapelig)
  • 69.
    Wikström, Gerhard
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Boman, K.
    Umea Univ, Res Unit, Med, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Olofsson, M.
    Umea Univ, Res Unit, Med, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Stålhammar, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Bergman, G. J.
    QuintilesIMS, Solna, Sweden..
    Tornblom, M.
    QuintilesIMS, Solna, Sweden..
    Wintzell, V.
    QuintilesIMS, Solna, Sweden..
    Balas, B.
    Novartis Pharma AG, Basel, Switzerland..
    Corda, S.
    Novartis Pharma AG, Basel, Switzerland..
    Lindmark, K.
    Umea Univ, Dept Publ Hlth & Clin Med, Ctr Heart, Umea, Sweden..
    Suboptimal dosing of common heart failure treatments in newly diagnosed patients with heart failure: a retrospective population-based cohort study in Sweden2017Inngår i: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 19, s. 54-54Artikkel i tidsskrift (Annet vitenskapelig)
  • 70.
    Wikström, Gerhard
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Kvidal, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Hagström, Emil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Livshotande hjärtsvikt av ADHD-medicinering: Fem patientfall beskrivs2012Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 109, nr 45, s. 2016-2018Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Five patients, three women and two men, with symptoms and signs of cardiomyopathy are presented. The common denominator for these patients was that they were all receiving medical treatment for attention deficit hyperactivity disorder. Although not proven a causal relationship between treatment for attention deficit hyperactivity disorder and development of cardiomyopathy is suggested. When medication for this disorder was stopped or reduced, together with conventional therapy for heart failure all patients normalized or improved their heart function and functional class. A short discussion follows where some of the likely mechanisms for this possible relationship are presented. We suggest a more thorough physical examination, history and follow up to avoid risk of developing cardiomyopathy when the above mentioned drugs are recommended for the treatment of attention deficit hyperactivity disorders.

  • 71.
    Wikström, Gerhard
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Lindmark, K.
    Umea Univ, Dept Publ Hlth & Clin Med, Ctr Heart, Umea, Sweden..
    Olofsson, M.
    Umea Univ, Dept Publ Hlth & Clin Med, Res Unit, Med, Umea, Sweden..
    Stålhammar, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Bergman, G. J.
    QuintilesIMS, Solna, Sweden..
    Tornblom, M.
    QuintilesIMS, Solna, Sweden..
    Wintzell, V.
    QuintilesIMS, Solna, Sweden..
    Wirta, S. Bruce
    Novartis Pharma AG, Basel, Switzerland..
    Balas, B.
    Novartis Pharma AG, Basel, Switzerland..
    Boman, K.
    Umea Univ, Dept Publ Hlth & Clin Med, Res Unit, Med, Umea, Sweden..
    Drug treatment patterns in patients newly diagnosed with heart failure: a retrospective population-based cohort study in Sweden2017Inngår i: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 19, nr Suppl. 1, s. 55-55Artikkel i tidsskrift (Annet vitenskapelig)
  • 72. Yilmaz, Mehmet B.
    et al.
    Grossini, Elena
    Silva Cardoso, Jose C.
    Edes, Istvan
    Fedele, Francesco
    Pollesello, Piero
    Kivikko, Matti
    Harjola, Veli-Pekka
    Hasslacher, Julia
    Mebazaa, Alexandre
    Morelli, Andrea
    le Noble, Jos
    Oldner, Anders
    Oulego Erroz, Ignacio
    Parissis, John T.
    Parkhomenko, Alexander
    Poelzl, Gerhard
    Rehberg, Sebastian
    Ricksten, Sven-Erik
    Rodriguez Fernandez, Luis M.
    Salmenpera, Markku
    Singer, Mervyn
    Treskatsch, Sascha
    Vrtovec, Bojan
    Wikström, Gerhard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Renal Effects of Levosimendan: A Consensus Report2013Inngår i: Cardiovascular Drugs and Therapy, ISSN 0920-3206, E-ISSN 1573-7241, Vol. 27, nr 6, s. 581-590Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Renal dysfunction is common in clinical settings in which cardiac function is compromised such as heart failure, cardiac surgery or sepsis, and is associated with high morbidity and mortality. Levosimendan is a calcium sensitizer and potassium channel opener used in the treatment of acute heart failure. This review describes the effects of the inodilator levosimendan on renal function. A panel of 25 scientists and clinicians from 15 European countries (Austria, Finland, France, Hungary, Germany, Greece, Italy, Portugal, the Netherlands, Slovenia, Spain, Sweden, Turkey, the United Kingdom, and Ukraine) convened and reached a consensus on the current interpretation of the renal effects of levosimendan described both in non-clinical research and in clinical study reports. Most reports on the effect of levosimendan indicate an improvement of renal function in heart failure, sepsis and cardiac surgery settings. However, caution should be applied as study designs differed from randomized, controlled studies to uncontrolled ones. Importantly, in the largest HF study (REVIVE I and II) no significant changes in the renal function were detected. As it regards the mechanism of action, the opening of mitochondrial K-ATP channels by levosimendan is involved through a preconditioning effect. There is a strong rationale for randomized controlled trials seeking beneficial renal effects of levosimendan. As an example, a study is shortly to commence to assess the role of levosimendan for the prevention of acute organ dysfunction in sepsis (LeoPARDS).

  • 73.
    Zemgulis, Vitas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Ronquist, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Bjerner, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Henze, Axel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Waldenström, Anders
    Thelin, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Wikström, Gerhard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Energy-related metabolites during and after induced myocardial infarction with special emphasis on the reperfusion injury after extracorporeal circulation2001Inngår i: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 171, nr 2, s. 129-143Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 74.
    Zemgulis, Vitas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Wikström, Gerhard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Bjerner, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Henze, Axel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Lahtinen, M.
    Waldenström, Anders
    Thelin, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Ronquist, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Discrepant outcome between myocardial energy-related metabolites and infarct size limitation during retroperfusion of the coronary sinus2001Inngår i: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 61, nr 8, s. 651-662Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    The basic idea of retroperfusion of the coronary sinus (RCS) is to ameliorate detrimental consequences of myocardial ischaemia. Several experimental models of RCS have been introduced, most with an emphasis on functional myocardial status. Since only few studies have been devoted to energy metabolic considerations and none to continuous monitoring of energy-related metabolites of myocardium during RCS, we here present such a study using microdialysis. This study comprised the following components: Coronary occlusion and drainage on the beating heart with RCS-assist (60 min), hypothermic (30 degrees C) extracorporeal circulation (ECC) and cardioplegia (45 min), reperfusion and rewarming to 38 degrees C on ECC (30 min). The microdialysis analytical outcome mainly reflected anaerobic energy metabolism in potentially ischaemic myocardium. Additionally, a pronounced increase of microdialysate content of lactate, pyruvate and guanosine was observed in non-ischaemic myocardium especially during the reperfusion phase. The planimetric calculation revealed an infarct size reduction from 69% to 19% and was not correlated to clear-cut improvements of potentially ischaemic myocardial energy metabolism. We conclude that prolonged (60 min) anaerobic energy metabolism does not pose an immediate threat to cell viability but could even sustain myocyte survival.

  • 75.
    Zemgulis, Vitas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Wikström, Gerhard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Henze, Axel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Waldenström, Anders
    Thelin, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Ronquist, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Nucleoside transport inhibition in ischemic myocardium results in enhanced taurine efflux2001Inngår i: European Journal of Pharmacology, ISSN 0014-2999, E-ISSN 1879-0712, Vol. 411, nr 1-2, s. 143-154Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    We measured with the microdialysis technique energy-related metabolites in ischemic myocardium over time in an experimental pig model. Emphasis was put on the dipyridamole effect when administered in the microdialysis probe inserted in ischemic myocardium. Not only adenosine but also taurine and pyruvate concentrations were significantly higher in the microdialysate during the periods of ischemia and extracorporeal circulation with cardioplegia. The enhanced efflux of taurine in ischemic myocardium induced by dipyridamole is a new finding. A mechanistic role of taurine in the prevention of Ca(2+) overload in ischemic myocytes is discussed. Also, taurine may have stimulatory effects on glycolysis in ischemic heart.

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