© 2000 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
β1 and β2-adrenergic receptor subtype effects in German shepherd dogs with inherited lethal ventricular arrhythmias
aDepartment of Pharmacology, Columbia University, College of Physicians and Surgeons, 630 West 168 Street, PH7W-321, New York, NY 10032, USA
bDepartment of Pediatrics, Columbia University, College of Physicians and Surgeons, New York, NY, USA
cCornell University, College of Veterinary Medicine, Ithaca, NY, USA
* Corresponding author. Tel.: +1-212-305-8754; fax: +1-212-305-8351 mrr1{at}columbia.edu
Objective: Delayed afterdepolarization-induced triggered activity originating in ventricular myocardium is a mechanism for some age-dependent, inherited ventricular tachycardias in a colony of German shepherd dogs. Methods: We used standard microelectrode techniques to study β-adrenergic receptor subtype modulation of the triggered activity in anteroseptal left ventricular myocardium from eleven of these dogs and seven unafflicted, age-matched German shepherd controls. Results: During sustained stimulation at cycle lengths of 300–4000 ms, 10–9–10–7 M isoproterenol concentration-dependently shortened action potential duration (APD) to 90% repolarization more in myocardium from afflicted than from unafflicted dogs. This shortening was prevented by a β1-blocker CGP20712A (10–7 M) while a β2-blocker ICI118551 (10–7 M) did not modify the effect of isoproterenol in either group. The β2-agonist zinterol 10–8–10–6 M had no effect on APD. Stimulation at a cycle length of 250 ms in the presence of 10–7 M isoproterenol induced more triggered AP in myocardium from afflicted than unafflicted dogs. β1-Blockade completely eliminated, while β2-blockade facilitated, and the β2-agonist zinterol did not induce triggered activity in the two groups. Conclusion: Isoproterenol effects on APD and triggered activity in the myocardium of dogs with inherited arrhythmias are due primarily to an abnormality of β1-adrenoceptor mediated signaling that is subject to β2-adrenergic modulation.
KEYWORDS Adrenergic (ant)agonists; Arrhythmia (mechanisms); Sudden death; Ventricular arrhythmias; Impulse formation
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