glycogen and Coronary-Stenosis

Scarring and remodeling of the left ventricle (LV) after myocardial infarction (MI) results in ischemic cardiomyopathy with reduced contractile function. Regional differences related to persisting ischemia may exist. We investigated the hypothesis that mitochondrial function and structure is altered in the myocardium adjacent to MI with reduced perfusion (MI

Topics: AMP-Activated Protein Kinases; Animals; Blotting, Western; Cardiomyopathies; Cell Respiration; Cicatrix; Coronary Stenosis; Electron Transport Complex I; Electron Transport Complex II; Electron Transport Complex IV; Glucose Transport Proteins, Facilitative; Glycogen; Magnetic Resonance Imaging; Microscopy, Electron; Microscopy, Fluorescence; Mitochondria, Heart; Myocardial Infarction; Myocardial Perfusion Imaging; Myocytes, Cardiac; Oxygen Consumption; Real-Time Polymerase Chain Reaction; RNA, Messenger; Stroke Volume; Sus scrofa; Swine; Ventricular Remodeling

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.

Topics: Adaptation, Physiological; Animals; Calcium-Binding Proteins; Calcium-Transporting ATPases; Calsequestrin; Chronic Disease; Coronary Circulation; Coronary Stenosis; Disease Models, Animal; Disease Progression; Glycogen; Hemodynamics; Ischemic Preconditioning, Myocardial; Microspheres; Myocardial Contraction; Myocardial Ischemia; Myocardial Reperfusion; Myocardial Stunning; Myocardium; Myofibrils; RNA, Messenger; Sarcoplasmic Reticulum; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Swine