Tumor necrosis factor-alph is released from the isolated heart undergoing ischemi and reperfusion

Objectives. The purpose of this study was to examine whether tumor necrosis factor-alph (TNF-alpha) is released directly from the ischemic myocardium undergoing reperfusion. Background. Tumor necrosis factor-alph is protein hormone produced by systemic leukocytes (primarily by activated macrophages). It has been implicated as systemic mediator in the development of septic shock and other pathologic conditions. Serum TNF-alph has also been detected in variety of cardiac disease states and after myocardial ischemia-reperfusion injury. Methods. Nine isolated rat hearts undergoing 30 min of perfusion, followed by warm cardioplegic arrest, 1 h of global ischemi and 30 min of reperfusion, were investigated using the modified Langendorff model. Results. Significant amounts of TNF-alph (752 ± 212 pmol/ml) were detected in the effluent during the first minute of reperfusion. Tumor necrosis factor-alph levels correlated with postischemic deterioration in peak systolic pressures (r = 0.7882, P = 0.012), dP/dt max (r = 0.6795, P = 0.044), time-pressure integral (r = 0.7661, P = 0.0016) and postischemic creatine kinase levels (r = 0.8367, P = 0.005). The deterioration in coronary flow, however, was inversely correlated with TNF-alph levels (r = −0.7581, P = 0.018). Conclusions. To our knowledge, this study is the first to suggest that the isolated rat myocardium synthesizes and releases TNF-alph in response to ischemi and reperfusion, which directly correlates with the postischemic deterioration in myocardial mechanical performance and the amount of cellular necrosis.