Myofibrillar disruption in hypocontractile myocardium showing perfusion-contraction matches and mismatches

1 Feinberg Cardiovascular Research Institute and the Departments of 2 Medicine, 3 Surgery, 4 Pediatrics, and 5 Cell and Molecular Biology, Northwestern University Medical School, Chicago, Illinois 60611-3008 Chronically instrumented dogs underwent 2- or 5-h regional reductions in coronary flow that were followed, respectively, by balanced reductions in myocardial contraction and O 2 consumption ("hibernation") and persistently reduced contraction despite normal myocardial O 2 consumption ("stunning"). Previously unidentified myofibrillar disruption developed during flow reduction in both experimental models and persisted throughout the duration of reperfusion (2-24 h). Aberrant perinuclear aggregates that resembled thick filaments and stained positively with a monoclonal myosin antibody were present in 34 ± 3.8% (SE) and 68 ± 5.9% of "hibernating" and "stunned" subendocardial myocytes in areas subjected to flow reduction and in 16 ± 2.5% and 44 ± 7.4% of subendocardial myocytes in remote areas of the same ventricles. Areas of myofibrillar disruption also showed glycogen accretion and unusual heterochromatin clumping adjacent to the inner nuclear envelope. The degrees of flow reduction employed were sufficient to reduce regional myofibrillar creatine kinase activity by 25-35%, but troponin I degradation was not evident. The observed changes may reflect an early, possibly reversible, phase of the myofibrillar loss characteristic of hypocontractile myocardium in patients undergoing revascularization. myocardial hibernation; stunning; apoptosis; stress proteins; myocardial ischemia