The protective effects of calcium antagonist and free radical scavenger against myocardial ischemic/reperfusion injury in the isolated rat heart.

Using the isolated working rat heart model, efficacy of the calcium antagonist and free radical scavengers against the myocardial injury induced by ischemia and reperfusion was investigated. In the calcium antagonist series, diltiazem was added to St. Thomas' Hospital cardioplegic solution. After 35 minutes of ischemia (37C) and 30 minutes of reperfusion, the dose response curve of postischemic recovery of aortic flow showed the bell-shaped pattern and the addition of 0.4 mg/L of diltiazem significantly increased the final recovery of aortic flow from the control value of 45.3 +/- 3.1% to 59.1 +/- 3.7% (P less than 0.01). However, the higher dose of diltiazem reduced the postischemic recoveries of heart rate and aortic flow probably due to its side effects of negative inotropic and chronotropic effect. In the free radical scavengers series, 100 mg/L of superoxide dismutase (SOD) and 10 mg/L of catalase (CAT) were added in the same experimental schedule. The addition of these enzymes significantly improved the postischemic recovery of aortic flow, and the best recovery was seen in the group receiving both SOD and CAT (72.9 +/- 3.9%, P less than 0.001). It was suggested that SOD and CAT have potential clinical application in preventing oxygen radical-mediated myocardial injury in the setting of open heart surgery.