Acute coronary artery occlusion-reperfusion-induced arrhythmias in rats, dogs and pigs: antiarrhythmic evaluation of quinidine, procainamide and lidocaine.
Arrhythmias which occur following either abrupt occlusion (CO) of the left anterior descending coronary artery (LAD), or rapid reperfusion (CR) of the same, were studied in rats, dogs and pigs. We found that all rats or pigs exhibited ventricular fibrillation (VF) during CO or after CR in contrast to dogs where more than 30% survived both procedures. In rats, the distribution in the onset of non-lethal arrhythmia or VF appeared to be uniform over the CO period, while in pigs and dogs the onset times clustered into two distinct groups. Also unlike dogs and pigs, the rat frequently (75%) underwent spontaneous defibrillation. Quinidine pretreatment (10 mg/kg i.v.) proved effective in protecting all three species from VF while procainamide (20 mg/kg i.v.) was effective only in rats and dogs. Lidocaine pretreatment (10 mg/kg i.v.) was effective in preventing VF in rats, but increased the incidence of CR-induced VF in dogs and significantly (P less than 0.01) reduced the mean time to VF during CO in pigs. However, lidocaine given immediately after CO in pigs did not reduce the time to VF suggesting that lidocaine given post-infarction would not increase the risk of VF, although the drug appears to be of no therapeutic benefit during the early occlusion period. Similarities in the action of lidocaine in pigs and dogs further  suggest that the mechanisms of CR-induced VF in dogs and CO-induced VF in pigs may be similar. These data also support a pivitol role of extracellular K+ accumulation of the production of early post-infarction arrhythmias. Thus, the arrhythmogenic as well as antiarrhythmic properties of the various drugs studied here may relate their known effects on potassium permeability in cell membranes.
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000209:etiology; D001794:Blood Pressure / Q000187:drug effects; D003327:Coronary Disease / Q000150:complications; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008012:Lidocaine / Q000627:therapeutic use*; D008297:Male; D010477:Perfusion; D011188:Potassium / Q000378:metabolism; D011342:Procainamide / Q000627:therapeutic use*; D011802:Quinidine / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013552:Swine
D008012:Lidocaine; D011802:Quinidine; D011342:Procainamide; D011188:Potassium