Beneficial effect of captopril against ischaemia-reperfusion injury in isolated guinea pig hearts.

摘要

The study was designed to clarify whether captopril, an angiotensin-coverting enzyme inhibitor, will reduce the injury of global ischaemia and reperfusion after cardioplegic arrest in isolated guinea pig hearts, in a modified Langendorff model. The hearts were randomly allocated into four groups (n = 10 in each) and subjected to 90 min of normothermic global ischemia, followed by 30 min of reperfusion; in all groups, cardioplegic arrest was achieved by administering St. Thomas's Hospital cardioplegic solution (STHCS). The first group was utilized as the control group. In the second group, captopril (200 mumol/L) was added to STHCS. In the third group, oral pretreatment was carried out (0.3 mg/kg captopril was given twice a day for 10 days). In the fourth group, oral pretreatment was achieved and captopril-enriched solution was applied in the first 5 min of reperfusion. Although the study groups showed better recovery of contractility than the control group, in the fourth group the hearts had the best left ventricular contractile function, where contractile force (g contractility/g heart weight) was 55.4% +/- 3.8% of the preischameic values. Groups I, II, and III achieved 31.0% +/- 3.2%, 41.6% +/- 3.8%, and 48.3% +/- 3.9% of their preischaemic contractile force values. Creatine kinase leakage was significantly lower and postischaemic coronary flows, too, were significantly higher in the fourth group. Coronary flow after reperfusion increased from 48.5 +/- 6.7 to 65.2 +/- 7.1 ml/min g heart in group 4 (p < 0.05). Myocardial lipid peroxides and glutathione contents showed that there was a correlation between the depletion of myocardial glutathione content and increased lipid peroxidation. These preliminary results showed that: the addition of captopril to reperfusion solution and oral preconditioning improved post-ischameic myocardial function and decreased myocardial injury.