An animal model of spontaneous arrhythmic death.
Ventricular arrhythmias and the proclivity for sudden death have been identified in German shepherd dogs. This disorder is inherited, and affected animals can be consistently produced from an established colony. The arrhythmias are most prevalent in young dogs between 22 and 26 weeks of age, with death most frequent at this same age. Death occurs most frequently during presumed sleep or at rest after exercise or excitement. The QT interval is not prolonged; however, more frequent notching of the T wave exists in affected dogs compared to control dogs. Polymorphic rapid nonsustained ventricular tachycardia occurs most frequently following long RR intervals. Accordingly, perturbations that decrease the heart rate or enhance sinus arrhythmia increase the incidence of ventricular arrhythmias. Because the arrhythmias are age, behavior, and heart rate dependent, the autonomic nervous system may play a role in their generation. As determined by metaiodobenzyl-guanidine scintigraphy and immunocytochemical staining of tyrosine hydroxylase, cardiac sympathetic innervation is regionally deficient in affected dogs. Evidence suggests that initiation of the ventricular arrhythmias is caused by early afterdepolarization (EAD)-induced triggered activity originating from left ventricular Purkinje fibers. Alpha 1-adrenergic stimulation provokes EADs in the Purkinje fibers and ventricular arrhythmias in the dogs. The development of EADs may be related to heterogeneity of repolarizing currents (Ito in particular) in affected dogs. From this canine model of spontaneous ventricular arrhythmias, the opportunity exists to investigate the interplay between abnormal development of cardiac innervation and the genesis of lethal ventricular arrhythmias.
Moïse
N S
NS
Department of Clinical Science, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853-6401, USA.nsm2@cornell.edu
Gilmour
R F
RF
Riccio
M L
ML
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D016757:Death, Sudden, Cardiac; D004195:Disease Models, Animal; D004285:Dogs