title: Effects of SQ 26,533 on reperfusion arrhythmias, ST-segment elevation and on infarct size in anesthetized dogs.
abstract: 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)
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000188:drug therapy*; D002415:Cats; D003327:Coronary Disease / Q000188:drug therapy*; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy*; D009281:Naphthalenes / Q000627:therapeutic use*; D010477:Perfusion; D013764:Tetrahydronaphthalenes / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000889:Anti-Arrhythmia Agents; D009281:Naphthalenes; D013764:Tetrahydronaphthalenes; C048333:SQ 26533