We studied the role of alpha1-adrenoceptors in the modulation of
ventricular 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 alpha1-adrenoceptor-subtype blockers
WB4101 (0.5 mg/kg i.v.) or
chloroethylclonidine (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 occlusion,
ventricular tachycardia and
ventricular fibrillation incidence did not differ among control,
WB4101 or
chloroethylclonidine (3 dogs with
ventricular fibrillation in each group and 0, 2 and 3 dogs respectively with
ventricular tachycardia), but ventricular premature depolarizations were significantly reduced by both interventions, and
nonsustained 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
chloroethylclonidine-treated, as above. Here, 9/10
chloroethylclonidine-treated animals developed
ventricular tachycardia and fibrillation during occlusion, whereas only 4/10 controls and 4/10 WB4101-treated animals did so (P < 0.05). In conclusion, during sinus rhythm, both types of alpha1-adrenoceptor subtype blockade significantly suppressed ventricular premature depolarizations and neither affected
ventricular tachycardia and fibrillation. In contrast, when heart rate was held constant,
chloroethylclonidine clearly enhanced the occurrence of
ventricular fibrillation during occlusion. These results suggest the alpha1-adrenoceptor subtype blocked by
chloroethylclonidine, but not that blocked by
WB4101, is capable of increasing the incidence of lethal arrhythmias that occur at rapid atrial rates during
ischemia.