Abstract
Creatine kinase (CK) isoenzymes MM, MB, and BB are located primarily in the cell cytosol, and increased CKMB in plasma is the hallmark of myocardial infarction. However, whether CK is released with reversible ischemic injury remains controversial. Here, we assessed plasma CK activity-cytosolic and mitochondrial CK-in serial samples (every 10 min for 60 min, then hourly or every 4 h for 48 h) from 46 conscious dogs after transient or sustained coronary occlusion. Four dogs were sham-operated (controls); four underwent sustained coronary occlusion (96 h); and 38 underwent transient coronary occlusion (10-40 min) followed by 48 h of reperfusion. In postmortem histological examination of the dogs' hearts by light and electron microscopy, we looked for ischemia or necrosis. The presence of cell swelling and glycogen depletion was indicative of ischemia, whereas the added presence of cell disruption indicated necrosis. Coronary occlusion for ≤20 min consistently increased plasma mitochondrial and total CK activity and produced histologically evident myocardial necrosis. In contrast, after 10 to 15 min of coronary occlusion, 12 of 14 animals, despite extensive severe reversible ischemia, showed no increase in plasma CK; the remaining 2, which had increased plasma CK, had subendocardial necrosis. Thus, cytosolic or mitochondrial CK is released from the heart only when there has been irreversible myocardial injury - a finding with significant diagnostic and therapeutic implications.