Long-term electrophysiological effects of regional cardiac sympathetic denervation of the neonatal dog

Objective: In many cardiac arrhythmias, both a triggering factor and a favo rable myocardial substrate are required. Whereas the-term modulator of the myocardial substrate is less well sympathetic nervous system may trigger ta chyarrhythmias its function as a Iona 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 shephe rd dogs with incomplete sympathetic innervation. Methods: Mongrel dogs unde rwent right cardiac stellectomy (RSX) within the first day of life and were terminally studied with control littermates at 5 months of age. Results: O n days 1-21 of life, RSX animals manifested significant QT prolongation on ECG and sudden, asystolic death. Beyond this age, QT intervals normalized a nd deaths did not occur. At 5 months, action potentials (AP) were recorded from Purkinje fibers (PF) and midmyocardial preparations in anteroseptal (A S) and posterobasal (PB) left ventricle. Early afterdepolarizations occurre d only in left ventricular PF from RSX dogs. Isoproterenol prolonged AP dur ation in AS and shortened it in PB of RSX but not control dogs. The inciden ce of isoproterenol-initiated triggered activity and the amplitude of delay ed 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 inhe rited deficits in sympathetic innervation and sudden death. This implicates the sympathetic nerves as long-term modulators of an arrhythmogenic substr ate. That 5-month-old RSX dogs did not experience tachyarrhythmias or sudde n death indicates that further anomalies - beyond those explicable by the s ubstrate change - must exist to induce sudden death. (C) 2001 Elsevier Scie nce B.V. All rights reserved.