Phospholipid alterations in canine ischemic myocardium. Temporal and topographical correlations with Tc-99m-PPi accumulation and an in vitro sarcolemmal Ca2+ permeability defect.

Abstract

Experimental myocardial ischemia produced in dogs by proximal left anterior descending coronary artery (LAD) ligation results in a small but measurable decrease in total phospholipid content in the subendocardium of the ischemic region. After 3 hours of fixed occlusion, there is a 10% decrease in total phospholipid content. Silica gel chromatography reveals this decrease to be reflected predominantly by decreases in phosphatidyl choline (PC) and phosphatidyl ethanolamine (PE). If technetium 99m stannous pyrophosphate (Tc-99m-PPi) is injected intravenously after various intervals of LAD occlusion and 10 minutes prior to Vh hours of reflow, there is a close temporal and topographical correlation between the extent of PE depletion and Tc-99m-PPi uptake. To measure the effects of phospholipid degradation on cardiac sarcolemmal membranes, an enriched sarcolemmal preparation was treated with an exogenous phospholipase (0.01 mg/ml). Phospholipid degradation, even without depleting total phospholipid content, resulted in more than a 50% increase in net Ca 2+ efflux from vesicles preloaded by Na + :Ca 2+ exchange. In addition, sarcolemmal vesicles isolated from ischemic myocardium after 3 hours of LAD occlusion have an increased Ca 2+ permeability and phosphatidyl choline depletion compared to vesicles obtained from the corresponding nonischemic myocardium. These studies suggest that an alteration in phospholipid metabolism is related closely to the development of irreversible damage in ischemic canine myocardium. The biochemical mechanism responsible for this relationship may be the degradation of sarcolemmal membrane phospholipids and the associated increase in sarcolemmal Ca 2+ permeability.