Role of C-jun N-terminal Kinase in the Mitochondria of Ischemia-Reperfusion Injury of Isolated Heart (LB648)

Background: Previous studies indicate that inhibition of JNK activation during heart reperfusion reduces cell death and infarct size. However, the studies could not eliminate off-target effects due to the use of non-specific JNK inhibitors. In the present study, we observed whether two mechanistically unrelated, specific JNK inhibitors, SU3327 and SR3306, would reduce damage from ischemia/reperfusion (IR) and improve cardiac function. Methods: Using the Langendorff model of ischemia-reperfusion, isolated rat hearts underwent 25 min of global ischemia followed by concurrent JNK inhibitor administration (2 and 10 µM for SU3327, 0.5 and 2 µM for SR3306) and 30 or 60 min of reperfusion. Throughout perfusion, we monitored cardiac function based on the percent recovery of left ventricular developed pressure, minimum and maximum rates of pressure change in the ventricle, and the rate pressure product. Myocardial damage was assessed by measuring lactate dehydrogenase activity in heart effluent. At the end of repe...