© 2001 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Long-term electrophysiological effects of regional cardiac sympathetic denervation of the neonatal dog
Departments of Pharmacology and Pediatrics, Center for Molecular Therapeutics, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA
* Corresponding author. Department of Pharmacology, Center for Molecular Therapeutics, College of Physicians and Surgeons of Columbia University, 630 West 168 Street, PH 7 West-321, New York, NY 10032, USA. Tel.: +1-212-305-8754; fax: +1-212-305-8351 mrr1{at}columbia.edu
Objective: In many cardiac arrhythmias, both a triggering factor and a favorable myocardial substrate are required. Whereas the sympathetic nervous system may trigger tachyarrhythmias, its function as a long-term modulator of the myocardial substrate is less well understood. Therefore, we tested the hypothesis that regional sympathetic denervation at birth would produce an abnormal myocardial substrate. The comparator was the substrate associated with inherited, lethal tachyarrhythmias at 5 months of age in German shepherd dogs with incomplete sympathetic innervation. Methods: Mongrel dogs underwent right cardiac stellectomy (RSX) within the first day of life and were terminally studied with control littermates at 5 months of age. Results: On days 1–21 of life, RSX animals manifested significant QT prolongation on ECG and sudden, asystolic death. Beyond this age, QT intervals normalized and deaths did not occur. At 5 months, action potentials (AP) were recorded from Purkinje fibers (PF) and midmyocardial preparations in anteroseptal (AS) and posterobasal (PB) left ventricle. Early afterdepolarizations occurred only in left ventricular PF from RSX dogs. Isoproterenol prolonged AP duration in AS and shortened it in PB of RSX but not control dogs. The incidence of isoproterenol-initiated triggered activity and the amplitude of delayed afterdepolarizations were greater in RSX than control dogs. Conclusion: Five months after RSX heterogeneous alterations of LV electrophysiological properties were similar to those previously observed in animals having inherited deficits in sympathetic innervation and sudden death. This implicates the sympathetic nerves as long-term modulators of an arrhythmogenic substrate. That 5-month-old RSX dogs did not experience tachyarrhythmias or sudden death indicates that further anomalies — beyond those explicable by the substrate change — must exist to induce sudden death.
KEYWORDS Arrhythmia (mechanisms); Autonomic nervous system; ECG; Membrane potential; Purkinje fiber; Ventricular arrhythmias