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 metabol ism and contraction during ischemia and reperfusion was investigated by mea ns of phosphorus 31-nuclear magnetic resonance (P-31-NMR) in Langendorff ra bbit hearts. Normothermic, 20-min, global ischemia was followed by 30 min o f postischemic reperfusion and JTV-519 was administered from 40 min prior t o the global ischemia. Adenosine triphosphate (ATP), creatine phosphate (PC r), inorganic phosphate (Pi), intracellular pH (pHi), left ventricular deve loped pressure (LVDP), left ventricular end-diastolic pressure (LVEDP) and coronary flow were measured. Fourteen hearts were divided into 2 experiment al groups of 7: Group I were controls and Group II were perfused with JTV-5 19 (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 showe d 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 r eperfusion between the 2 groups. In conclusion, JTV-519 had a significant b eneficial effect on myocardial energy metabolism and relaxation during both myocardial ischemia and reperfusion.