We investigated the effects of coenzyme Q10 and verapamil, either alone or in combination, on cardiac function impaired by repeated ischemic arrests and reperfusion in the isolated rat heart. In the group with a single ischemic arrest, the aortic flow, cardiac output, stroke volume, coronary flow, and heart rate recovered well (72% to 100% of the prearrest values). In the repeated-arrest group, the recovery of aortic flow (24%), cardiac output (30%), stroke volume (40%), or coronary flow (63%) was much poorer than that in the single-arrest group. Pretreatment with coenzyme Q10 given intraperitoneally improved aortic flow, cardiac output, stroke volume, coronary flow, and heart rate. The addition of verapamil to the reperfusion solution also protected the cardiac function with a decrease in heart rate. However, combination therapy with coenzyme Q10 and verapamil further increased the recoveries of aortic flow, cardiac output, stroke volume, and coronary flow to 57%, 61%, 77%, and 84%, respectively, which were better than the values after treatment with coenzyme Q10 or verapamil alone. We, therefore, suggest that treatment with coenzyme Q10 or verapamil, alone or in combination, in addition to St. Thomas' Hospital solution effectively protects cardiac function impaired by repeated ischemic arrests and reperfusion.