Published online before print October 3, 2002, doi: 10.1161/01.RES.0000040396.79379.77
© 2002 American Heart Association, Inc.
Integrative Physiology |
Dissociation of Regional Adaptations to Ischemia and Global Myolysis in an Accelerated Swine Model of Chronic Hibernating Myocardium
From the VA Western New York Healthcare System (J.A.F., J.M.C.), Buffalo, NY; the Department of Medicine and the Department of Physiology and Biophysics (S.A.T., J.A.F., G.S., J.M.C.), University at Buffalo; and the Department of Molecular Cell Biology (M.B.), Cardiovascular Research Institute Maastricht, the Netherlands.
Correspondence to John M. Canty, Jr, MD, Biomedical Research Building, Room 347, Department of Medicine, University at Buffalo, 3435 Main St, Buffalo, NY 14214. E-mail canty{at}buffalo.edu
We tested the hypothesis that an acute critical limitation in coronary flow reserve could rapidly recapitulate the physiological, molecular, and morphological phenotype of hibernating myocardium. Chronically instrumented swine were subjected to a partial occlusion to produce acute stunning, followed by reperfusion through a critical stenosis. Stenosis severity was adjusted serially so that hyperemic flow was severely reduced yet always higher than the preocclusion resting level. After 24 hours, resting left anterior descending coronary artery (LAD) wall thickening had decreased from 36.3±4.0% to 25.5±3.7% (P<0.05), whereas resting flow had remained normal (67±6 versus 67±8 mL/min, respectively). Although peak hyperemic flow exceeded the prestenotic value, resting flow (45±10 mL/min) and LAD wall thickening (17.0±5.0%) progressively decreased after 2 weeks, when physiological features of hibernating myocardium had developed. Regional reductions in sarcoplasmic reticulum proteins were present in hibernating myocardium but absent in stunned myocardium evaluated after 24 hours. Histological analysis showed an increase in connective tissue along with myolysis (myofibrillar loss per myocyte >10%) and increased glycogen typical of hibernating myocardium in the LAD region (33±3% of myocytes from animals with hibernating myocardium versus 15±4% of myocytes from sham-instrumented animals, P<0.05). Surprisingly, the frequency of myolysis was similar in normally perfused remote regions from animals with hibernating myocardium (32±7%). We conclude that the regional physiological and molecular characteristics of hibernating myocardium develop rapidly after a critical limitation in flow reserve. In contrast, the global nature of myolysis and increased glycogen content dissociate them from the intrinsic adaptations to ischemia. These may be related to chronic elevations in preload but appear unlikely to contribute to chronic contractile dysfunction.
Key Words: hibernating myocardium • stunned myocardium • myocardial ischemia • myofibrillar loss
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