CHLOROETHYLCLONIDINE INCREASES THE INCIDENCE OF LETHAL ARRHYTHMIAS DURING CORONARY-OCCLUSION IN ANESTHETIZED DOGS

We studied the role of alpha(1)-adrenoceptors in the modulation of ven tricular tachycardia and fibrillation in chloralose-anesthetized dogs subjected to 30 min left anterior descending coronary artery occlusion . Study groups were control, and those treated with the alpha(1)-adren oceptor-subtype blockers WB4101 (0.5 mg/kg i.v.) or chloroethylclonidi ne (1.9 mg/kg i.v.). For the first set of experiments all animals were in sinus rhythm and heart rate was slower in the chloroethylclonidine -pretreated animals than the WB4101-treated group (P < 0.05). During o cclusion, ventricular tachycardia and ventricular fibrillation inciden ce did not differ among control, WB4101 or chloroethylclonidine (3 dog s with ventricular fibrillation in each group and 0, 2 and 3 dogs resp ectively with ventricular tachycardia), but ventricular premature depo larizations were significantly reduced by both interventions, and nons ustained ventricular tachycardia was suppressed by WB4101. In a second set of experiments, animals were atrially paced at a cycle length of 300 ms, and divided into control, WB4101-treated or chloroethylclonidi ne-treated, as above. Here, 9/10 chloroethylclonidine-treated animals developed ventricular tachycardia and fibrillation during occlusion, w hereas only 4/10 controls and 4/10 WB4101-treated animals did so (P < 0.05). In conclusion, during sinus rhythm, both types of alpha(1)-adre noceptor subtype blockade significantly suppressed ventricular prematu re depolarizations and neither affected ventricular tachycardia and fi brillation. In contrast, when heart rate was held constant, chloroethy lclonidine clearly enhanced the occurrence of ventricular fibrillation during occlusion. These results suggest the alpha(1)-adrenoceptor sub type blocked by chloroethylclonidine, but not that blocked by WB4101, is capable of increasing the incidence of lethal arrhythmias that occu r at rapid atrial rates during ischemia.