Cardioprotective effect of a novel cyclohexane dicarboximide derivative, ST-6, against ischemia/reperfusion injury

Blockade of sodium overload during ischemia and reperfusion plays an import ant role in cardioprotection. The present study was undertaken to determine whether or not a novel cyclohexane dicarboximide derivative, ST-6, which r eveals sodium channel blockade, may protect the heart from ischemia/reperfu sion injury. Isolated rat hearts were subjected to 30 min of ischemia follo wed by a 60-min reperfusion. Treatment with 10 and 30 muM ST-6 enhanced the postischemic recovery of left ventricular developed pressure, attenuated t he rise in left ventricular end-diastolic pressure, and restored high-energ y phosphate levels of the ischemic/reperfused heart. This improvement was a ssociated with reduction of the release of creatine kinase and purine nucle osides and bases from the reperfused heart. Tissue sodium content of the is chemic as well as reperfused hearts was increased. This increase was partia lly reversed by treatment with ST-6. ST-6 had the ability to reduce V-max o f the action potential of the left ventricular muscle. These results sugges t that this agent is capable of reducing ischemia/reperfusion injury of the heart, probably due to attenuation in sodium overload during ischemia and reperfusion. Drug Dev. Res. 51:20-28, 2000. (C) 2000 Wiley-Liss, Inc.