Pharmacologic preconditioning of JTE-607, a novel cytokine inhibitor, attenuates ischemia-reperfusion injury in the myocardium

Background: Myocardial ischemia-reperfusion injury is a main cause of postoperative cardiac dysfunction, and a burst of proinflammatory cytokines, such as tumor necrosis factor α, interleukin 1β, interleukin 6, and interleukin 8, plays a pivotal role. Recently, JTE-607 has been reported as a potent inhibitor of the multiple inflammatory cytokines in the endotoxin shock mouse model. In this study we proved the hypothesis that JTE-607 might attenuate myocardial ischemia-reperfusion injury in a rat model. Methods: The isolated rat hearts in the JTE-607 preconditioning group (J group, n = 8) or control group (C group, n = 8) were subjected to warm ischemia (37°C) for 30 minutes, followed by 60 minutes of reperfusion with the Langendorff perfusion system. Results: Left ventricular developed pressure and maximum dp/ dt after reperfusion were significantly improved in the J group than in the C group (P < .01). Creatine phosphokinase leakage is significantly lower in the J group (P < .05). Moreover, the tissue cytokine levels, such as tumor necrosis factor α, interleukin 6, and interleukin 8, in the myocardium were significantly lower in the J group than in the C group (P < .05). Conclusion: These results suggested that the pharmacologic preconditioning of JTE-607 inhibits a burst of endogenous cytokines in the myocardium, resulting in the improvement of cardiac function after ischemia-reperfusion injury. Thus JTE-607 might be a novel therapeutic strategy for the protection of postoperative cardiac dysfunction in cardiac surgery.