Effect of a novel cardioprotective agent, JTV-519, on metabolism, contraction and relaxation in the ischemia - Reperfused rabbit heart

The effect of a novel cardioprotective agent, JTV-519 on myocardial metabolism and contraction during ischemia and reperfusion was investigated by means of phosphorus 31-nuclear magnetic resonance (P-31-NMR) in Langendorff rabbit hearts. Normothermic, 20-min, global ischemia was followed by 30 min of postischemic reperfusion and JTV-519 was administered from 40 min prior to the global ischemia. Adenosine triphosphate (ATP), creatine phosphate (PCr), inorganic phosphate (Pi), intracellular pH (pHi), left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (LVEDP) and coronary flow were measured. Fourteen hearts were divided into 2 experimental groups of 7: Group I were controls and Group II were perfused with JTV-519 (10(-6) mol/L). During ischemia, Group II showed a significant (p<0.01) inhibition of the increase in Pi and LVEDP and the decrease in ATP and pHi, compared with Group I. After postischemic reperfusion, Group II also showed a significant (p<0.01) improvement in ATP and pHi as compared with Group I. There were no differences in LVDP or coronary flow during ischemia and reperfusion between the 2 groups. In conclusion, JTV-519 had a significant beneficial effect on myocardial energy metabolism and relaxation during both myocardial ischemia and reperfusion.