Attenuation of ischemia--reperfusion injury by enalapril maleat.
1. The aim of this study was to investigate the effects of enalapril maleate on ischemia-reperfusion injury of the myocardium, after cardioplegic arrest in isolated guinea pig hearts, in a modified Langendorff model. 2. Animals were subjected to 90 min of normothermic global ischemia, followed by 30 min of reperfusion. Cardioplegic arrest was achieved by administering St. Thomas Hospital cardioplegic solution (STHCS). 3. The hearts were randomly allocated into four groups (n=8 in each group). The first group was utilized as control. In the second group, oral pretreatment was made (0.2 mg/kg enalapril maleat was given twice a day for 10 days). In the third group, enalapril maleat (1 micromol/l) was added to STHCS. In the fourth group, hearts were arrested with enalapril maleat-enriched STHCS, and enalapril maleat-enriched (1 micromol/l) Krebs-Henseleit solution was applied during the reperfusion period. 4. Although the study groups showed better recovery of contractility than did the control group, in the last group, the hearts had the best recovery of left ventricular systolic function, where dp/dt maximum was 89.7+/-6.9% of the preischemic values. Group 1, group 2 and group 3 achieved 44.2+/-4.5%, 79.4+/-5.8% and 68.1+/-6.7% of their preischemic dp/dt values. A similar observation was found for left ventricular developed pressure (LVDP); LVDP values were 52.4+/-2.1% (in group 1), 79.6+/-2.8% (in group 2), 72.8+/-4.6% (in group 3) and 86.7+/-5.8% (in group 4) of control after reperfusion. Creatine kinase leakage was significantly lower and postischemic coronary flows were significantly higher in group 4. 5. We concluded that usage of enalapril maleat in the reperfusion period was more effective for improving myocardial recovery after cardioplegic arrest. The additional protective effects of enalapril maleat not only were by angiotensin-converting-enzyme-inhibition-dependent coronary vasodilation and thiol-dependent limitation of oxidative injury, but could also be related to an oxygen-free-radical-scavenging effect.
Department of Thoracic and Cardiovascular Surgery, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
R
R
Doğan
B
B
Farsak
M
M
Tuncer
E
E
Demirpençe
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002314:Cardioplegic Solutions; D004353:Drug Evaluation, Preclinical; D004656:Enalapril / Q000627:therapeutic use*; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*
D000806:Angiotensin-Converting Enzyme Inhibitors; D002314:Cardioplegic Solutions; D004656:Enalapril