Membrane changes induced by early myocardial ischemia in the dog

Sarcolemmal and mitochondrial phospholipids were extracted from normally perfused and ischemic regions of the dog heart and the composition of these extracts was analyzed. Relatively pure sarcolemmal fraction obtained from myocardium subjected to 3 h of ischemia exhibited a significantly lower concentration of phospholipids than that obtained from normal myocardium. In particular, phosphatidylcholine and phosphatidylethanolamine were reduced by approximately 33%. The fatty acid content in the sarcolemmal phospholipid fraction was also reduced by approximately 30% without any change in the relative composition. In the mitochondrial fraction, the relative phospholipid composition was also altered by ischemia; the major components (phosphatidylcholine, phosphatidylethanolamine, and cardiolipin) being reduced by approximately 15-20%. An attempt was made to correlate these biochemical changes with ultrastructural lesions observed electron microscopically. These observations revealed extensive regional variability and a wide heterogeneity in the extent of ultrastructural damage evident in the different organelles even in a single cell. This may suggest that ischemic damage, in the early stages, may advance at widely varying rates in different regions. Our findings demonstrate that significant biochemical and structural disorganization occurs during 3 h of ischemia in the myocardium and raise the possibility that one of the initiating events is the activation of sarcolemmal and mitochondrial phospholipases.