HETEROGENEOUS SYMPATHETIC INNERVATION IN GERMAN-SHEPHERD DOGS WITH INHERITED VENTRICULAR ARRHYTHMIA AND SUDDEN CARDIAC DEATH

Background Recently, a colony of German shepherd dogs with inherited s pontaneous cardiac arrhythmias and associated sudden death has been de veloped and characterized. Due to the median age of onset of the arrhy thmia (4.5 months), the tendency for the arrhythmia to occur during RE M sleep or after exercise, and the absence of structural heart disease , we hypothesized a developmental abnormality of the sympathetic inner vation to the heart. Methods and Results We studied 11 dogs from this colony, ranging in age from 6 months to 6 years, and four 7-month-old German shepherd dogs unrelated to the colony as controls. We imaged th e distribution of functional myocardial sympathetic innervation and pe rfusion with [I-123]metaiodobenzylguanidine (MIBG) and Tl-201, respect ively. Sympathetic nerve distribution was evaluated morphologically by immunocytochemical localization of tyrosine hydroxylase. All of the h earts showed evidence of a regional decrease in MIBG uptake, ranging f rom 5.3% to 53.4% of the myocardium, whereas control dogs showed homog eneous MIBG uptake. Immunocytochemical studies on sections from region s with decreased MIBG uptake showed a striking paucity of nerves compa red with regions with normal MIBG uptake, confirming denervation. When the dogs were grouped into those with (n=6) and without (n=5) evidenc e of ventricular tachycardia on ambulatory EGG, the group with ventric ular tachycardia showed 35+/-16.5% denervation, whereas the group with out ventricular tachycardia showed 12+/-5.6% denervation (P<.02). Conc lusions Abnormal heterogeneous sympathetic innervation exists in these dogs with inherited ventricular arrhythmia and sudden cardiac death. Mechanisms relating the presence and extent of regional denervation to the incidence of ventricular arrhythmia remain to be defined.