(Circulation. 1997;96:1337-1342.)
© 1997 American Heart Association, Inc.
Articles |
Heterogeneous Sympathetic Innervation in German Shepherd Dogs With Inherited Ventricular Arrhythmia and Sudden Cardiac Death
From the Cardiovascular Research Institute, School of Medicine, University of California at San Francisco (M.W.D., R.J.L., P.C.U., M.C.C., C.A.S.), and the Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY (N.S.M.).
Correspondence to Michael W. Dae, MD, Box 0252, Room L-340, University of California at San Francisco, San Francisco, CA 94143. E-mail michael_dae{at}radmac1.ucsf.edu
Background Recently, a colony of German shepherd dogs with inherited spontaneous cardiac arrhythmias and associated sudden death has been developed and characterized. Due to the median age of onset of the arrhythmia (4.5 months), the tendency for the arrhythmia to occur during REM sleep or after exercise, and the absence of structural heart disease, we hypothesized a developmental abnormality of the sympathetic innervation 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 the distribution of functional myocardial sympathetic innervation and perfusion with [123I]metaiodobenzylguanidine (MIBG) and 201Tl, respectively. Sympathetic nerve distribution was evaluated morphologically by immunocytochemical localization of tyrosine hydroxylase. All of the hearts showed evidence of a regional decrease in MIBG uptake, ranging from 5.3% to 53.4% of the myocardium, whereas control dogs showed homogeneous MIBG uptake. Immunocytochemical studies on sections from regions with decreased MIBG uptake showed a striking paucity of nerves compared with regions with normal MIBG uptake, confirming denervation. When the dogs were grouped into those with (n=6) and without (n=5) evidence of ventricular tachycardia on ambulatory ECG, the group with ventricular tachycardia showed 35±16.5% denervation, whereas the group without ventricular tachycardia showed 12±5.6% denervation (P<.02).
Conclusions 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.
Key Words: arrhythmia • catecholamines • imaging • nervous system • scintigraphy
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