Chronic hibernating myocardium in sheep can occur without degenerating events and is reversed after revascularization |
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| Affiliation: | 1. CARIM, Maastricht University, Maastricht, The Netherlands;2. Electron Microscopy Unit at CRISP;3. Department of Molecular Cell Biology;4. Department of Cardiac Surgery, Katholieke Universiteit Leuven, Leuven, Belgium;5. Department of Experimental Cardiology, KU Leuven, Leuven, Belgium;1. The Fingerland Department of Pathology, Charles University Faculty of Medicine and Faculty, Hospital Hradec Králové, Czech Republic;2. Department of Cardiovascular Medicine I, Charles University Faculty of Medicine and Faculty, Hospital Hradec Králové, Czech Republic;1. CNR Institute of Clinical Physiology, Laboratory of Cardiovascular Biochemistry, Pisa, Italy;2. Scuola Superiore Sant’Anna, Pisa, Italy;3. CNR Institute of Clinical Physiology, Cardiovascular Department, Niguarda Cà Granda Hospital, Milan, Italy;4. CardioThoracic and Vascular Department, “A. De Gasperis” Niguarda Ca’ Granda Hospital, Milan, Italy;1. Department of Cardiology, Bezmialem Foundation University, Istanbul, Turkey;2. Department of Cardiology and Angiology, University Clinic Erlangen, Germany;3. Department of Pathology, Medical School Hannover, Hannover, Germany;1. Department of Anatomical Pathology, Marqués de Valdecilla University Hospital, Medical Faculty, University of Cantabria and IDIVAL, Santander, Spain;2. Diagnostic Radiology Service, Marqués de Valdecilla University Hospital, Santander Spain;3. Service of Urology, Marqués de Valdecilla University Hospital, Medical Faculty, University of Cantabria and IDIVAL, Santander, Spain;1. Department of Pathology, Hospital de Especialidades, CMN La Raza, Calle Seris s/n, Col. La Raza, C.P. 02990, Delegación Azcapotzalco, México D.F., Mexico;2. Department of Pathology, San Cecilio University Hospital. Avenida Madrid 11, Granada, Spain;3. Department of Cardiology and Echocardiogram, Hospital de Especialidades, CMN La Raza, Calle Seris s/n, Col. La Raza, C.P. 02990, Delegación Azcapotzalco, México D.F., Mexico |
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| Abstract: | IntroductionOur goal was to show that blunting of myocardial flow reserve is mainly involved in adaptive chronic myocardial hibernation without apparent cardiomyocyte degeneration.Methods and resultsSheep chronically instrumented with critical multivessel stenosis and/or percutaneous transluminal coronary angioplasty (PTCA)-induced revascularization were allowed to run and feed in the open for 2 and 5 months, respectively. Regional myocardial blood flow (MBF) with colored microspheres, regional and global left ventricular function and dimensions (2D echocardiography), and myocardial structure were studied. In sheep with a critical stenosis, a progressive increase in left ventricular end-diastolic and end-systolic cavity area and a decrease in fractional area change were found. Fraction of wall thickness decreased in all left ventricular wall segments. MBF was slightly but not significantly decreased at rest at 2 months. Morphological quantification revealed a rather small but significant increase in diffusely distributed connective tissue, cardiomyocyte hypertrophy, and presence of viable myocardium of which almost 30 % of the myocytes showed depletion of sarcomeres and accumulation of glycogen. The extent of myolysis in the transmural layer correlated with the degree of left ventricular dilation. Structural degeneration of cardiomyocytes was not observed. Balloon dilatation (PTCA) of one of the coronary artery stenoses at 10 weeks revealed recovery of fraction of wall thickness and near normalization of global subcellular structure at 20 weeks.ConclusionThese data indicate that chronic reduction of coronary reserve by itself can induce ischemic cardiomyopathy characterized by left ventricular dilatation, depressed regional and global function, adaptive chronic myocardial hibernation, reactive fibrosis and cardiomyocyte hypertrophy in the absence of obvious degenerative phenomena.SummaryReduction of myocardial flow reserve due to chronic coronary artery stenosis in sheep induces adaptive myocardial hibernation without involvement of degenerative phenomena. |
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