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Celiprolol does not protect against ventricular tachycardia or sudden death in the conscious canine: a comparison with pindolol in assessing the role of intrinsic sympathomimetic activity

AC Uprichard, LG Chi, JM Kitzen, JJ Lynch, JW Frye and BR Lucchesi

University of Michigan Medical School, Department of Pharmacology, Ann Arbor.

The antiarrhythmic and antifibrillatory effects of the beta-1 adrenoceptor antagonist celiprolol were evaluated in a chronic canine model of myocardial infarction and sudden death. Programmed electrical stimulation (PES) was performed in conscious animals 3 to 5 days after a 2-hr occlusion/reperfusion of the left anterior descending coronary artery. Dogs in which PES resulted in a reproducible nonsustaining or sustained ventricular tachycardia (VT) were randomized to receive i.v. celiprolol (3 mg/kg, n = 10) or vehicle (n = 10). PES and measurement of electrophysiologic (parameters were repeated after 30 min and the animals were entered into the sudden death protocol by introducing a 150-microA anodal current to the lumen of the left circumflex coronary artery via a surgically implanted silver wire electrode. Celiprolol failed to prevent the induction of VT, and the outcome of the sudden death protocol did not differ from vehicle with respect to either sudden (within 1 hr of ischemia) or delayed (greater than 1 hr) mortality. VT cycle length and ventricular refractoriness were prolonged (P less than .05) by celiprolol, but other electrophysiologic parameters were unaffected. Heart rate was not altered after drug, but celiprolol antagonized the ischemia-induced increase in rate seen in the vehicle group. Similar electrophysiologic results and mortality data were apparent in a third group of dogs which received pindolol (0.09 mg/kg, n = 8). The failure of both drugs to protect against ischemic ventricular fibrillation in a model in which beta adrenoceptor antagonism has previously proved beneficial may be due in part to related cardiostimulant properties shared by celiprolol and pindolol.

Volume 251, Issue 2, pp. 571-577, 11/01/1989
Copyright © 1989 by American Society for Pharmacology and Experimental Therapeutics






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Copyright © 1989 by the American Society for Pharmacology and Experimental Therapeutics.