Protective effect of lisinopril against ischemia-reperfusion injury in isolated guinea pig hearts

Background. In order to determine whether angiotensin-converting enzyme inh ibitors (ACEI's) attenuate ischemia-reperfusion injury, we investigated and compared the effects of lisinopril via different routes of administration in an isolated guinea pig heart model of ischaemia reperfusion, Methods. The effect of lisinopril cardioplegia, oral pretreatment with lisi nopril and lisinopril enriched reperfusion solution on myocardium after a n ormothermic global ischemia of 90 minutes and 30 minutes of reperfusion in the modified Langendorff model was randomly studied in 4 groups (n=8 in eac h). In all groups, cardioplegic arrest was achieved by administering St. Th omas' Hospital Cardioplegic Solution (STHCS). The first group was utilized as the control. In the second group, hearts were arrested with lisinopril ( 1 mu mol/L) enriched STHCS. In the third group, animals were pre treated wi th oral lisinopril (0.2 mg/kg/twice a day) for ten days. In the last group hearts were again pretreated with oral lisinopril (Like in Group 3) and the heart were reperfused with Lisinopril enriched (1 mu mol/L) Krebs-Henselei t solution during the reperfusion period. Results, Contractility, which was expressed as contractile force (g contrac tility/g heart weight), was preserved better in the study groups, In the la st group, the hearts had the best left ventricular contractile function, wh ere contractile force was 58.4%+/-4.82% of the preischaemic values. In Grou p I, Group II and Group m they achieved 29.5%+/-5.6%, 41.9%+/-4.9%, and 55. 3%+/-5.8% of their preischaemic contractile force values respectively. Crea tine kinase leakage was significantly lower and also postischaemic coronary flows were significantly higher in the 4(th) group. Coronary now after rep erfusion increased from 48.0 +/-6.2 to 68.0 +/-4.51 ml/min.g.heart, in Grou p IV (p<0.05). Conclusions, Myocardial MDA and GSH contents showed that there was a correl ation between the depletion of myocardial GSH content and increased Lipid p eroxidation, The myocardial GSH content indicates that the best results wer e obtained in the last group as compared to the other groups. These prelimi nary results showed that oral preconditioning improved postischaemic myocar dial function and decreased myocardial injury. Because the best results wer e achieved in the last group, it can be suggested that lisinopril may also play a protective role againts reperfusion injury.