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-mu-g kg-1, i.v.), junctional tachycardia (128 +/- 20-mu-g kg-1, i.v.), multiform ventricular premature beats (157 +/- 21-mu-g kg-1, i.v.) and sustained VT (220 +/- 23-mu-g kg-1, i.v.). 3 Doses of Clon (i.v.) required for termination of VT following i.v. Yoh (62.9 +/- 5.2-mu-g kg-1) or i.a. Yoh (88.5 +/- 16.3-mu-g kg-1) were higher than those for termination of VT without Yoh administration (28.3 +/- 6.2-mu-g 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-mu-g 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.