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 myocard ial metabolism and contraction during ischemia and reperfusion was examined by phosphorus 31-nuclear magnetic resonance (P-31-NMR) in Langendorff rabb it hearts. After normothermic 15 min global ischemia, 60 min of postischemi c reperfusion was carried out. TAK-044 and/or temocaprilat was administered from 40 min prior to the global ischemia. Adenosine triphosphate (ATP), cr eatine phosphate, inorganic phosphate, pH, left ventricular systolic develo ped pressure (LVDev.P), left ventricular end-diastolic pressure (LVEDP) and coronary flow were measured. Twenty-eight hearts were divided into 4 exper imental groups consisted of seven hearts each: Group I consisted of control s, Group II was perfused with TAK-044 (10(-6) mol/L), Group III was perfuse d with temocaprilat (10(-6) mol/L), and Group TV was perfused with TAK-044 (10(-6) mol/L) in combination with temocaprilat (10(-6) mol/L). Group 11 sh owed 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 Grou p 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 imp rovement on recovery of ATP during postischemic reperfusion (86+/-3%) compa red with the other 3 groups. There were no differences in LVDev.P, LVEDP an d coronary flow among these groups. In conclusion, TAK-044 in combination w ith temocaprilat had a significant potentiation on myocardial metabolism du ring both ischemia and reperfusion.