Termination of digitalis-induced ventricular tachycardias by clonidine involves central alpha 2-adrenoceptors in cats.
1. Effects of intravenous (i.v.) and intravertebral arterial (i.a.) administration of the alpha 2-adrenoceptor agonist, clonidine (Clon) and its antagonist, yohimbine (Yoh, 0.5 mg kg-1, i.v.; 0.05 mg kg-1, i.a.), on ventricular tachycardia (VT) induced by intravenous acetylstrophanthidin (AS) were studied in cats anaesthetized with intraperitoneal chloralose. 2. AS dose-dependently produced cardiac arrhythmias including complete atrioventricular conduction block (118 +/- 14 micrograms kg-1, i.v.), junctional tachycardia (128 +/- 20 micrograms kg-1, i.v.), multiform ventricular premature beats (157 +/- 21 micrograms kg-1, i.v.) and sustained VT (220 +/- 23 micrograms kg-1, i.v.). 3. Doses of Clon (i.v.) required for termination of VT following i.v. Yoh (62.9 +/- 5.2 micrograms kg-1) or i.a. Yoh (88.5 +/- 16.3 micrograms kg-1) were higher than those for termination of VT without Yoh administration (28.3 +/- 6.2 micrograms kg-1). Doses of Clon (i.a.) required for termination of VT without or with i.a. Yoh administration were 5.8 +/- 1.0 or 14.8 +/- 3.7 micrograms kg-1, respectively, and they were significantly different. 4. These experiments demonstrate that either i.v. or i.a. Yoh antagonizes the antiarrhythmic effect of Clon on AS-induced VT. Since small doses of Clon administered i.a. act predominantly on the central nervous system, we suggest that its antiarrhythmic effect is likely to be on central alpha 2-adrenoceptors in the central nervous system.
Chen
S A
SA
Division of Cardiology, Taipei Veterans General Hospital, Taiwan.
Liu
R H
RH
Ting
T H
TH
Chang
M S
MS
Chiang
B N
BN
Kuo
J S
JS
D000818:Animals; D000889:Anti-Arrhythmia Agents; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D003000:Clonidine / Q000494:pharmacology*; D004071:Digitalis Glycosides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D004594:Electrophysiology; D005260:Female; D008297:Male; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D013327:Strophanthidin / Q000031:analogs & derivatives / Q000494:pharmacology; D013610:Tachycardia / Q000139:chemically induced / Q000188:drug therapy*; D015016:Yohimbine / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D004071:Digitalis Glycosides; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D013327:Strophanthidin; C004681:acetylstrophanthidin; D003000:Clonidine