To determine whether gallopamil (D600), a methoxy derivative of verapamil, administered immediately before coronary artery reperfusion reduces the extent of myocardial hemorrhage and necrosis, the left anterior descending coronary artery was occluded for 3 h and reperfused for 3 h in anesthetized, open-chest dogs. To quantify the extent of the hypoperfused zone (HZ), 99mTc-labeled albumin microspheres were injected into the left atrium 1 min after occlusion. Five minutes before reperfusion, dogs were randomly assigned to a control group or a gallopamil-treated group that immediately after assignment received 0.08 mg/kg gallopamil followed by a continuous infusion of 0.2 mg/kg/h for 3 h. Three hours after reperfusion, the left ventricle was cut into slices for triphenyltetrazolium chloride staining and autoradiography. There were no differences in the extent of the HZ between the two groups. Gallopamil significantly reduced the extent of myocardial necrosis from 81.3 +/- 4.2% (n = 8) of the HZ in the control to 46.1 +/- 13.1% (n = 9, p less than 0.05) in the treated group. The extent of gross hemorrhage was significantly smaller in the gallopamil-treated group (1.3 +/- 0.9% of the left ventricle or 3.1 +/- 1.8% of the HZ, p less than 0.01) as compared with the control group (6.2 +/- 1.4% of the left ventricle or 20.0 +/- 4.6% of the HZ). Thus, gallopamil administered immediately before coronary artery reperfusion limited infarct size and reduced the extent of myocardial hemorrhage.