Effects of SQ 26,533 on reperfusion arrhythmias, ST-segment elevation and on infarct size in anesthetized dogs
Saini, R.K.; Fulmor, I.E.; Parham, C.S.; Antonaccio, M.J.
Journal of Pharmacology and Experimental Therapeutics 237(1): 1-8
1986
ISSN/ISBN: 0022-3565 PMID: 3958960 Document Number: 285033
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.