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Cardiovascular Research 1999 42(1):65-79; doi:10.1016/S0008-6363(98)00333-2
© 1999 by European Society of Cardiology
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Copyright © 1999, European Society of Cardiology

Abnormal cardiac repolarization and impulse initiation in German shepherd dogs with inherited ventricular arrhythmias and sudden death

Eugene A Sosunova,1, Evgeny P Anyukhovskya,1, Alexei Shvilkina, Motoki Haraa, Susan F Steinberga, Peter Danilo, Jr.a, Michael R Rosena,*, N Sydney Möiseb, Jocelyn Mérotc, Vincent Probstc, Flavien Charpentierc, Yves Legeayc and Hervé Le Marecc

aDepartments of Pharmacology, Pediatrics and Medicine, College of Physicians and Surgeons of Columbia University, 630 West 168 Street, PH 7 West-321 New York, NY 10032, USA
bDepartment of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA
cLaboratoire de Physiopathologie & Pharmacologie Cellulaires & Moléculaires, Centre Hospitalo-Universitaire de Nantes and Laboratoire de Médecine, Ecole, Vétérinaire de Nantes, Nantes, France

* Corresponding author. Tel.: +1-212-305-8754; fax: +1-212-305-8351; e-mail: emf3@columbia.edu

Objective: We tested the hypothesis that delayed afterdepolarization (DAD)-associated rhythms in German shepherd dogs with reduced anteroseptal left ventricular (LV) sympathetic innervation derive from abnormal β-adrenergic receptor effector coupling. Methods and Results: In anteroseptal LV midmyocardium of afflicted dogs, β-receptor density was greater than that in normal dogs (P<.05), with affinity being equal in both groups. Basal and maximum isoproterenol (ISO) stimulated adenylyl cyclase activity of anteroseptal LV of afflicted dogs was greater than that in normal dogs (P<.05). Isolated anteroseptal M cell preparations of afflicted dogs studied with microelectrodes showed abnormal lengthening, rather than shortening of action potential duration in response to ISO, as well as a 61% incidence of 10–7 mol/l ISO-induced triggered activity as compared to 12% in normals (P<.05). In contrast, there was no difference between afflicted and control dogs in triggered activity, β-receptors or adenylyl cyclase activity in a normally innervated region of the ventricles. Conclusion: In this model there is an increase in β-receptor density and β-adrenergic stimulation of adenylyl cyclase and of triggered activity in anteroseptal myocardium but not in a normally innervated region of the heart. Hence, abnormal β-adrenergic signal transduction appears associated with the neural abnormality identified in dogs with inherited VT.

KEYWORDS Autonomic nervous system; Receptors; Ventricular arrhythmias

1 Contributed equally as first author.


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