Alterations in regional myocardial distribution and arrhythmogenic effects of aprindine produced by coronary artery occlusion in the dog.
Little information exists regarding the effects of coronary artery occlusion on the distribution and actions of antiarrhythmic agents. We administered aprindine to dogs before, 5 min after, and 24 h after one-stage left anterior descending coronary artery (LAD) occlusion. Coronary artery occlusion performed after aprindine administration slowed the rate of disappearance of aprindine from the ischaemic zone compared with the normal zone, so that ischaemic zone aprindine concentrations averaged more than twice normal zone aprindine concentrations 1 h after LAD occlusion. When LAD occlusion was performed before aprindine administration, ischaemic zone aprindine concentrations were initially less than 15% of normal zone aprindine concentrations and increased with time to approach half of normal zone aprindine concentrations 70 min after LAD occlusion. Seventeen of 35 dogs (49%) receiving aprindine before LAD occlusion experienced sustained ventricular tachycardia or ventricular fibrillation, compared with 5/34 (14%) receiving aprindine immediately after LAD occlusion (P less than 0.01), 1/10 (10%) undergoing LAD occlusion without receiving aprindine (P less than 0.05) and 0/16 receiving aprindine without LAD occlusion (P less than 0.01). Aprindine administered 24 h after CO reduced premature ventricular complexes from a mean of 35 to 12 per 100 beats (P less than 0.01) occlusion importantly modifies the regional myocardial distribution of aprindine and its effects on ventricular arrhythmias after coronary artery occlusion.
D000818:Animals; D001073:Aprindine / Q000378:metabolism / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000209:etiology; D003326:Coronary Circulation; D003327:Coronary Disease / Q000150:complications / Q000188:drug therapy*; D004285:Dogs; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects*; D007192:Indenes / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism
D007192:Indenes; D001073:Aprindine