Effect of an endothelin receptor antagonist and an angiotensin converting enzyme inhibitor on metabolism and contraction in the ischemic and reperfused rabbit heart.

The effect of an endothelin (ET) A/ETB receptor antagonist, TAK-044, and/or an angiotensin converting enzyme (ACE) inhibitor, temocaprilat, on myocardial metabolism and contraction during ischemia and reperfusion was examined by phosphorus 31-nuclear magnetic resonance (31P-NMR) in Langendorff rabbit hearts. After normothermic 15 min global ischemia, 60min of postischemic reperfusion was carried out. TAK-044 and/or temocaprilat was administered from 40 min prior to the global ischemia. Adenosine triphosphate (ATP), creatine phosphate, inorganic phosphate, pH, left ventricular systolic developed pressure (LVDev.P), left ventricular end-diastolic pressure (LVEDP) and coronary flow were measured. Twenty-eight hearts were divided into 4 experimental groups consisted of seven hearts each: Group I consisted of controls, Group II was perfused with TAK-044 (10(-6) mol/L), Group III was perfused with temocaprilat (10(-6) mol/L), and Group IV was perfused with TAK-044 (10(-6) mol/L) in combination with temocaprilat (10(-6) mol/L). Group II showed a more early recovery of ATP during postischemic reperfusion (82+/-3%) compared with Group I (71+/-3%). Group III showed a significant inhibition of the decrease in ATP during global ischemia (54+/-3%) compared with Group I (45+/-3%). Group IV also showed a significant marked inhibition of the decrease in ATP during global ischemia (59+/-5%) and a more significant improvement on recovery of ATP during postischemic reperfusion (86+/-3%) compared with the other 3 groups. There were no differences in LVDev.P, LVEDP and coronary flow among these groups. In conclusion, TAK-044 in combination with temocaprilat had a significant potentiation on myocardial metabolism during both ischemia and reperfusion.