ACTIVATED COMPLEMENT DIRECTLY MODIFIES THE PERFORMANCE OF ISOLATED HEART-MUSCLE CELLS FROM GUINEA-PIG AND RAT

The complement system has been implicated in the pathogenesis of cardi ovascular disorders including ischemia and atherosclerosis. Selective deposition of C5b-9, the membrane attack complex of complement, has be en histochemically documented in human myocardium early after reperfus ion of ischemic areas and in infarcted zones. However, functional sequ elae of the C5b-9 complex binding to myocardial cells have not been id entified. Insertion of C5b-9 complexes into the membrane of other cell types can generate transient changes in membrane permeability in the absence of cell lysis. We demonstrate in beating isolated adult guinea pig and rat cardiac myocytes that human derived C5b-9 can transiently augment in a dose-dependent manner both basal cytosolic calcium conce ntration and calcium transients, resulting in a temporary increase in contractility. If similar changes occur in human heart cells in vivo, they could significantly affect myocardial performance and contribute to functional abnormalities seen in ischemia and other pathological co nditions associated with complement activation.