Effects of SQ 26,533 on reperfusion arrhythmias, ST-segment elevation and on infarct size in anesthetized dogs

The antiarrhythmic, antifibrillatory activities and the ability of SQ 26,533 to reduce infarct size were investigated in the canine models of reperfusion arrhythmias. In model 1, halothane-anesthetized dogs were subjected to acute occlusion of left circumflex coronary artery (LCX) for 30 min followed by reperfusion. SQ 26,533 infused at 50 micrograms/kg/min for 45 min significantly reduced (78%) the incidence of ventricular ectopic beats during the 30-min ligation of LCX. In addition, four of seven dogs (57%) survived after reperfusion, in contrast to 100% mortality observed in untreated animals. In model 2, left anterior descending artery under pentobarbital anesthesia was occluded for 20 min and released. SQ 26,533 (2.5 mg/kg i.v.) given 1 hr before occlusion significantly reduced (81%) ventricular ectopic beats during acute occlusion and four of five animals (80%) survived left anterior descending artery reperfusion, unlike saline controls (100% mortality). Similar efficacy was seen in a feline model of reperfusion arrhythmias. The model 3 animals under pentobarbital anesthesia were occluded for 60 min followed by reperfusion of the LCX in the presence of critical stenosis. SQ 26,533 (2.5 mg/kg every 90 min) given 50 min after LCX occlusion not only resulted in a significant reduction (91%) of postreperfusion ventricular ectopic beats for the entire 5-hr observation period but also significantly reduced (42%) the infarct size at 24 hr. Antiarrhythmic doses of SQ 26,533 caused minimal hemodynamic changes, except for a marked decrease in heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)