Effect of angiotensin converting enzyme inhibitor and angiotensin II type 1 receptor antagonist on metabolism and contraction in ischemia-reperfused rabbit heart

The effect of angiotensin converting enzyme (ACE) inhibitor, temocaprilat a nd/or angiotensin II type 1 (ATI) receptor antagonist, CV-11974 on myocardi al metabolism and contraction during ischemia and reperfusion was examined by phosphorus 31-nuclear magnetic resonance (P-31-NMR) in Langendorff rabbi t hearts. After normothermic 15 min global ischemia, postischemic reperfusi on of 60 min was carried out. Temocaprilat and/or CV-11974 were administere d from 40 min prior to the global ischemia. Adenosine triphosphate (ATP), c reatine phosphate (PCr), inorganic phosphate (Pi), intracellular pH (pHi), left ventricular developed pressure (LVDevP), left ventricular end-diastoli c pressure (LVEDP) and coronary flow were measured. Twenty-eight hearts wer e divided into 4 experimental groups consisting of 7 hearts each: group I c onsisted of controls, group II was perfused with temocaprilat (10(-6) mol/L ), group III was perfused with CV-11974 (10(-6) mol/L), and group IV was pe rfused with temocaprilat (10(-6) mol/L) in combination with CV-11974 (10(-6 ) mol/L). Groups II and III showed a significant (p<0.05) inhibition of an overshoot phenomenon of PCr during postischemic reperfusion compared with g roup I. Group IV also showed a more pronounced significant (p<0.01) inhibit ion of the overshoot of PCr during reperfusion compared with group I. Group s II, III and IV showed a significant (p<0.05) inhibition of the decrease i n ATP during global ischemia (59+/-2, 54+/-3 and 54+/-7%, respectively) com pared with group I (45+/-r3%). Groups III and IV showed a significant (p<0. 05) early recovery of ATP during reperfusion (81+/-2, 80+/-6%) compared wit h group I (71+/-3%) and group II (73+/-2%). Group IV showed no more signifi cant recovery in ATP than group III. There were no differences in LVDeVP, L VEDP and coronary flow among these groups. In conclusion, temocaprilat in c ombination with CV-11974 has significant potential for improving myocardial energy metabolism during both myocardial ischemia and reperfusion.