FAILURE OF CAPTOPRIL TO ATTENUATE MYOCARDIAL DAMAGE, NEUTROPHIL ACCUMULATION, AND MORTALITY FOLLOWING CORONARY-ARTERY OCCLUSION AND REPERFUSION IN RAT

Captopril, a sulfhydryl-containing angiotensin-converting enzyme inhib itor, has bee suggested as possessing antiischemic and antiinflammator y properties. To test th hypothesis that captopril may prevent neutrop hil-induced myocardial injury during acut myocardial infarction (AMI), the authors subjected rats to coronary occlusion for thirty minutes a nd reperfusion for twenty-four hours (MI) or to sham operation (sham M I). Oral captopril (100 mg/kg) or vehicle was administered thirty minu tes before corona occlusion. The effect of captopril on mean arterial blood pressure was assessed in separate group of animals (n=8). Infarc t size and neutrophil accumulation in myocardium were determined b mea suring creatine phosphokinase depletion and myeloperoxidase (MPO) acti vity, respectively, in the left ventricular free wall (LVFW). Animals treated with 100 mg/kg of captopril exhibited significant reduction in mean arterial blood pressure compared with vehicle-treated animals (P < 0.01). Compared with vehicle-treated animals, administration of 100 mg/kg of captopril to MI animals attenuated neither twenty-four-hour mortality (56% vs 52%, respectively), nor infarct size (36 +/- 7% vs 3 4% +/- 7% respectively), nor MPO activity (1.0 +/- 0.17 vs 1.26 +/- 0. 19). Thus, in the present experiment captopril did not reduce neutroph il-induced myocardial damage following coronary occlusion and reperfus ion. These findings may be partly explained by the negative effect of captopril on arterial blood pressure during AMI.