The cardioprotective effects of lidoflazine, a drug with calcium homeostatic properties, were studied in 12 dogs (6 drug-treated and 6 controls) subjected to 1-hour normothermic global ischemia. None of the control dogs could be weaned from the extracorporeal bypass after 30 minutes of reperfusion. In contrast, all acutely pre-treated animals were able to support their own circulation. Recovery of pre-ischemic values in this group was 97 +/- 3% for systolic aortic pressure, 69 +/- 7% for diastolic aortic pressure, 97 +/- 10% for left ventricular pressure, and 84 +/- 11% for cardiac output. Electron microscopy and calcium cytochemistry were done on left ventricular biopsies taken before, during, and after ischemic arrest. In the control group, severe damage to the sarcolemma and the mitochondria was found at the end of the ischemic period and became more prominent after 5 and 30 minutes of reperfusion. There was great accumulation of calcium in the damaged mitochondria. In the lidoflazine-treated dogs, these lesions were largely prevented. These findings suggest a strong cardioprotective effect of lidoflazine during severe myocardial ischemia.