Chloroethylclonidine increases the incidence of lethal arrhythmias during coronary occlusion in anesthetized dogs.
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.
Geller
J C
JC
Department of Pharmacology and Pediatrics, College of Physicians and Surgeons of Columbia University, New York, 10032 USA.
Cua
M
M
Prieto
L
L
Guo
S D
SD
Danilo
P
P
Rosen
M R
MR
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology*; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D004285:Dogs; D005260:Female; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications*; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D018340:Receptors, Adrenergic, alpha-1; C051731:chlorethylclonidine; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D003000:Clonidine