A role for prostaglandins in reperfusion-induced myocardial injury?

Abstract

Restoration of flow to hearts made ischemic for 60 min is known to produce accelerated tissue injury. In these studies, reperfusion produced an enhanced enzyme [creatine phosphokinase (CPK) and lactate dehydrogenase] efflux, development of contracture, and reduced mitochondrial oxidative phosphorylation. These effects were associated with prostaglandin (PG) production as measured by 6-keto-PGF1 alpha efflux from the heart. Three nonsteroidal antiinflammatory agents--indomethacin, aspirin, and mefenamic acid--that inhibit the cyclooxygenase-dependent conversion of arachidonic acid to PGs reduced most aspects of dysfunction associated with reperfusion. In addition, three glucocorticoids--cortisol, dexamethasone, and methylprednisolone--that prevent substrate availability for cyclooxygenase also significantly decreased CPK efflux, but had variable effects on other parameters. These studies suggest that endogenous PGs produced in the heart may contribute to the dysfunction associated with reperfusion of the ischemic myocardium.