Increased Myocardial Tumor Necrosis Factor-α in a Crystalloid-Perfused Model of Cardiac Ischemia-Reperfusion Injury

Background. The heart is a tumor necrosis factor-α (TNF-α)–producing organ. Recent basic experimental and clinical evidence suggests that TNF-α is an important mediator of myocardial injury during acute myocardial infarction, chronic heart failure, cardiac allograft rejection, and cardiopulmonary bypass operations. Although it is known that the myocardium itself is capable of producing TNF-α in response to endotoxin, it is unknown whether there is an increase in myocardial tissue TNF-α levels after ischemia-reperfusion injury. We hypothesized that ischemia-reperfusion induces the production of TNF-α by the heart. Methods. To avoid blood-borne TNF-α as a potentially confounding variable, we examined myocardial TNF-α production in a crystalloid-perfused model of cardiac ischemia-reperfusion injury. Isolated rat hearts were perfused with crystalloid solution and subjected to ischemia-reperfusion. Postischemic myocardial TNF-α was measured using an enzyme-linked immunosorbent assay and correlated with developed pressure, coronary flow, end-diastolic pressure, and creatine kinase loss (assay of activity in coronary effluent). Results. Ischemia-reperfusion induced a marked increase in myocardial TNF-α that was associated with decreased myocardial contractility and coronary flow and with increased end-diastolic pressure and postischemic creatine kinase loss. Conclusions. The heart produces TNF-α in response to ischemia-reperfusion. Ischemia-induced TNF-α production may contribute to postischemic myocardial stunning, necrosis, or both. Strategies designed to limit ischemia-induced myocardial TNF-α production may have therapeutic utility in the settings of planned myocardial ischemic events.