Captopril, an ACE inhibitor, for optimizing reperfusion after acute myocardial infarction.
Captopril is an angiotensin-converting enzyme inhibitor that has been reported to be effective in salvaging post-ischemic reperfused myocardium by its ability to function as a free radical-scavenging agent. A study was performed in the isolated porcine-heart model evaluating the influence of pretreatment with captopril on salvage of myocardium after an induced myocardial infarction. Measurement was carried out of regional and global myocardial function, myocardial high-energy phosphate levels, creatine kinase release, malonaldehyde formation, and 6-keto-prostaglandin F1 alpha generation. In an in vitro preparation, the influence of captopril for scavenging various free radicals was evaluated. A dose-response curve was carried out using this free radical-generating system and differing levels of captopril. Results of the study demonstrate that pretreatment with captopril at a 45-mumol/L level reduced reperfusion injury in the pig heart model. This was manifested by improved cardiac performance, a reduction in creatine kinase release, and reduced malonaldehyde generation. In vitro evaluation of captopril and its free radical-scavenging ability indicated that it is a weak scavenger of superoxide anions (O2-) but behaves as a potent scavenger of hydroxyl radicals (-OH) as well as hypohalite radicals (OCl-). Based on the influence of captopril in reducing lipid peroxidation (decreased malonaldehyde formation) and its documented ability to scavenge -OH as well as OCl-, it is suggested that myocardial preservation in a postinfarction model is due primarily to its free radical-scavenging activity, primarily of the potent free radicals -OH and OCl-.
Department of Surgery, University of Connecticut School of Medicine, Farmington.
R M
RM
Engelman
J A
JA
Rousou
J
J
Iyengar
D K
DK
Das
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002216:Captopril / Q000627:therapeutic use*; D003326:Coronary Circulation / Q000187:drug effects; D003402:Creatine Kinase / Q000096:biosynthesis; D005260:Female; D016166:Free Radical Scavengers; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000473:pathology*; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D013552:Swine
D016166:Free Radical Scavengers; D015121:6-Ketoprostaglandin F1 alpha; D000255:Adenosine Triphosphate; D002216:Captopril; D003402:Creatine Kinase