Pretreatment with captopril improves myocardial recovery after cardioplegic arrest.
Among the interventions designed to limit postischemic oxidative injury, those that enhance the myocardial content of thiol groups are attractive because thiols are powerful antioxidant. Indeed, part of the protection afforded by the angiotensin-converting enzyme (ACE) inhibitor captopril in regional myocardial ischemia is attributed to its thiol group. This study assesses the effects of captopril in a surgically relevant model of global ischemic arrest. Thirty rats were implanted subcutaneously (s.c.) with osmotic pumps that allowed continuous delivery of captopril (total dose 75 mg), enalapril (a nonthiol-containing ACE inhibitor, total dose 7.5 mg) or saline in 48 h. Drug concentrations were equipotent in their effect on angiotensin I (ANGI) pressor response. Hearts were then excised, perfused under isovolumic conditions, and subjected to 90-min cardioplegic arrest at 30 degrees C followed by 1-h reperfusion. Pre- and postischemic coronary flows were significantly higher to a similar extent in the two drug-pretreated groups than in controls. However, captopril-pretreated hearts had the best recovery of contractility (dP/dtmax; 3,590 +/- 74 versus 2915 +/- 64 mm Hg s-1 in the enalapril group, p less than 0.001), and diastolic pressure (13.7 +/- 0.9 mm Hg vs. 20.0 +/- 1.6 mm Hg in the enalapril group, p less than 0.05). We conclude that pretreatment with ACE inhibitors improves myocardial recovery after cardioplegic arrest and that captopril is more effective than enalapril. The additional protection afforded by captopril was not flow mediated, suggesting that the cardioprotective effects of this drug not only involve an ACE inhibition-dependent coronary vasodilation but could be related to a thiol-dependent limitation of oxidative injury.
Menasché
P
P
Department of Cardiovascular Surgery, Hôpital Lariboisière, Paris, France.
Grousset
C
C
Peynet
J
J
Mouas
C
C
Bloch
G
G
Piwnica
A
A
D000818:Animals; D002216:Captopril / Q000627:therapeutic use*; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy / Q000517:prevention & control; D003971:Diastole / Q000187:drug effects / Q000502:physiology; D004656:Enalapril / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006324:Heart Arrest, Induced / Q000379:methods*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
D004656:Enalapril; D002216:Captopril