Effects of bepridil on regional myocardial ischemia and comparison with verapamil

Abstract

This study was designed to assess the efficacy of bepridil in reducing regional myocardial ischemia and to compare its efficacy with that of verapamil. Forty-five anesthetized, open-chest dogs were subjected to three 5-minute occlusions of the left anterior descending coronary artery (LAD), each followed by 45 minutes of reperfusion. Eleven dogs (group 1) served as controls. In 10 dogs, bepridil, 5 mg/kg, was administered before the third occlusion (group 2). In 11 dogs, verapamil was administered before the third occlusion (group 3). In each dog, on-line intramyocardial hydrogen ion concentration and carbon dioxide tension were measured in the myocardial segment supplied by the LAD. Regional myocardial contractility was assessed in this area with 2 pairs of ultrasonic crystals inserted to determine percent segmental shortening. Regional myocardial blood flow was determined during each occlusion by washout of xenon-127. The increase in hydrogen ion concentration and carbon dioxide tension did not change from occlusion 2 to occlusion 3 in the control group. Both bepridil and verapamil elicited a significant reduction in the extent of regional ischemia, evidenced by a reduction in the accumulation of hydrogen ions, in occlusion 3 vs occlusion 2. Systolic bulging occurred during all occlusions and the periods of reperfusion were not sufficient to allow complete recovery of regional function. Bepridil and verapamil each caused a significant increase in percent segmental shortening (both p < 0.025), and verapamil effected a significant improvement of function during occlusion 3 compared with occlusion 2. Neither bepridil nor verapamil affected regional myocardial blood flow. These data show that bepridil's salutary effect on regional myocardial ischemia is similar to, but less potent than, that of verapamil. This salutary effect is achieved neither through a reduction in myocardial contractility nor through an increase in myocardial oxygen supply. It is probably a result of a reduction in the rate-pressure product and prevention of the deleterious effect of calcium overload on the mitochondria.