| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(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
This article has been cited by other articles:
 |
|
 |
|
  E. A. Sosunov, M. N. Obreztchikova, E. P. Anyukhovsky, N.S. Moise, P. Danilo Jr., R. B. Robinson, and M. R. Rosen Mechanisms of {alpha}-adrenergic potentiation of ventricular arrhythmias in dogs with inherited arrhythmic sudden death Cardiovasc Res, March 1, 2004; 61(4): 715 - 723. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. N. Obreztchikova, E. A. Sosunov, E. P. Anyukhovsky, N. S. Moise, R. B. Robinson, and M. R. Rosen Heterogeneous Ventricular Repolarization Provides a Substrate for Arrhythmias in a German Shepherd Model of Spontaneous Arrhythmic Death Circulation, September 16, 2003; 108(11): 1389 - 1394. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Members of the Sicilian Gambit New Approaches to Antiarrhythmic Therapy, Part I: Emerging Therapeutic Applications of the Cell Biology of Cardiac Arrhythmias Circulation, December 4, 2001; 104(23): 2865 - 2873. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Members of the Sicilian Gambit New approaches to antiarrhythmic therapy; emerging therapeutic applications of the cell biology of cardiac arrhythmias Eur. Heart J., December 1, 2001; 22(23): 2148 - 2163. [Abstract] [PDF]
|
|
|
|
|
|
Members of the Sicilian Gambit New approaches to antiarrhythmic therapy: emerging therapeutic applications of the cell biology of cardiac arrhythmias Cardiovasc Res, December 1, 2001; 52(3): 345 - 360. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. F Gilmour Jr. Life out of balance: The sympathetic nervous system and cardiac arrhythmias Cardiovasc Res, September 1, 2001; 51(4): 625 - 626. [Full Text] [PDF]
|
|
|
|
|
|
E. A. Sosunov, E. P. Anyukhovsky, R. Z. Gainullin, A. Plotnikov, P. Danilo Jr., and M. R. Rosen Long-term electrophysiological effects of regional cardiac sympathetic denervation of the neonatal dog Cardiovasc Res, September 1, 2001; 51(4): 659 - 669. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.-S. Chen, L. S Chen, J.-M. Cao, B. Sharifi, H. S Karagueuzian, and M. C Fishbein Sympathetic nerve sprouting, electrical remodeling and the mechanisms of sudden cardiac death Cardiovasc Res, May 1, 2001; 50(2): 409 - 416. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E.N Simantirakis, V.K Prassopoulos, S.I Chrysostomakis, G.E Kochiadakis, S.I Koukouraki, J.P Lekakis, N.S Karkavitsas, and P.E Vardas Effects of asynchronous ventricular activation on myocardial adrenergic innervation in patients with permanent dual-chamber pacemakers. An I123-metaiodobenzylguanidine cardiac scintigraphic study Eur. Heart J., February 2, 2001; 22(4): 323 - 332. [Abstract] [PDF]
|
|
|
|
 |
|
 J. Merot, V. Probst, M. Debailleul, U. Gerlach, N. S. Moise, H. Le Marec, and F. Charpentier Electropharmacological characterization of cardiac repolarization in German shepherd dogs with an inherited syndrome of sudden death: abnormal response to potassium channel blockers J. Am. Coll. Cardiol., September 1, 2000; 36(3): 939 - 947. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Matsunari, U. Schricke, F. M. Bengel, H.-U. Haase, P. Barthel, G. Schmidt, S. G. Nekolla, A. Schoemig, and M. Schwaiger Extent of Cardiac Sympathetic Neuronal Damage Is Determined by the Area of Ischemia in Patients With Acute Coronary Syndromes Circulation, June 6, 2000; 101(22): 2579 - 2585. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Yoshioka, D.-W. Gao, M. Chin, C. Stillson, E. Penades, M. Lesh, W. O’Connell, and M. Dae Heterogeneous Sympathetic Innervation Influences Local Myocardial Repolarization in Normally Perfused Rabbit Hearts Circulation, March 7, 2000; 101(9): 1060 - 1066. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N.S. Moise Inherited arrhythmias in the dog: potential experimental models of cardiac disease Cardiovasc Res, October 1, 1999; 44(1): 37 - 46. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A Sosunov, E. P Anyukhovsky, A. Shvilkin, Motoki Hara, S. F Steinberg, P. Danilo Jr., M. R Rosen, N Sydney Moise, J. Merot, V. Probst, et al. Abnormal cardiac repolarization and impulse initiation in German shepherd dogs with inherited ventricular arrhythmias and sudden death Cardiovasc Res, April 1, 1999; 42(1): 65 - 79. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Olgin, H. J. Sih, S. Hanish, J. V. Jayachandran, J. Wu, Q. H. Zheng, W. Winkle, G. K. Mulholland, D. P. Zipes, and G. Hutchins Heterogeneous Atrial Denervation Creates Substrate for Sustained Atrial Fibrillation Circulation, December 8, 1998; 98(23): 2608 - 2614. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. Pacioretty and R. F. Gilmour Jr. Restoration of transient outward current by norepinephrine in cultured canine cardiac myocytes Am J Physiol Heart Circ Physiol, November 1, 1998; 275(5): H1599 - H1605. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Bru-Mercier, E. Deroubaix, D. Rousseau, A. Coulombe, and J.-F. Renaud Depressed transient outward potassium current density in catecholamine-depleted rat ventricular myocytes Am J Physiol Heart Circ Physiol, April 1, 2002; 282(4): H1237 - H1247. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. F. Steinberg, S. Alcott, E. Pak, D. Hu, L. Protas, N. S. Moise, R. B. Robinson, and M. R. Rosen beta 1-Receptors increase cAMP and induce abnormal Cai cycling in the German shepherd sudden death model Am J Physiol Heart Circ Physiol, April 1, 2002; 282(4): H1181 - H1188. [Abstract] [Full Text] [PDF]
|
|