Effect of ramiprilat or captopril on myocardial infarct size: assessment in canine models of ischemia alone and ischemia with reperfusion.
Cardioprotective effects of the angiotensin-converting enzyme inhibitors captopril and ramiprilat were studied in two in vivo canine models of myocardial ischemic injury: 90 min of regional ischemia with 18 h reperfusion (protocol I) and 6 h of continuous ischemia without reperfusion (protocol II). In protocol I, neither ramiprilat (50 micrograms/kg) nor captopril (5 mg/kg + 0.25 mg/kg/h) reduced infarct size after 18 h of reperfusion (vs. controls). In protocol II, drugs were administered directly into both left anterior descending coronary artery and left circumflex branch. Compared to controls, continuous intracoronary administration of ramiprilat (40 ng/kg/min) or captopril (400 ng/kg/min) did not reduce infarct size. Thus neither captopril nor ramiprilat protected the heart from injury under conditions of ischemia with reperfusion or ischemia without reperfusion.
Department of Pharmacology, University of Michigan Medical School, Ann Arbor, USA. shawn_black@merck.com
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D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002216:Captopril / Q000494:pharmacology / Q000627:therapeutic use*; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D004285:Dogs; D005069:Evaluation Studies as Topic; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology* / Q000517:prevention & control*; D017202:Myocardial Ischemia / Q000503:physiopathology / Q000517:prevention & control; D015425:Myocardial Reperfusion / Q000009:adverse effects; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000503:physiopathology; D017257:Ramipril / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D000806:Angiotensin-Converting Enzyme Inhibitors; C052549:ramiprilat; D002216:Captopril; D017257:Ramipril