A colony of German Shepherd dogs with a syndrome that is provocatively similar to the sudden infant death syndrome (SIDS) has been established. These dogs have an inherited spontaneous ventricular arrhythmia that leads to sudden death in approximately 40% of affected dogs. The ventricular arrhythmia is exacerbated during sleep. Furthermore, most dogs with a witnessed death have died during sleep and most were 4 to 8 months of age. It is hypothesized that the arrhythmias (and death) are precipitated by an imbalance of autonomic innervation, and that this imbalance is a developmental abnormality that rectifies with advancing age. Initially, 24-hour ambulatory electrocardio-graphic (Holter) monitoring will be used to determine the temporal evolution of the spontaneous ventricular arrhythmia in affected dogs. Affected dogs also will be studied with time-lapsed video recordings during the Holter monitoring to verify the exacerbation of ventricular arrhythmias during sleep. Subsequently, electrophysiological and anatomical substrates for autonomic imbalance in the heart will be evaluated. To determine if selected electrophysiologic indices are consistent with autonomic imbalance, the corrected QT interval and heart rate variability will be compared in affected and unaffected dogs during sleep and wakefulness. Invasive electrophysiologic studies also will be used to determine if the arrhythmias can be induced with programmed-stimulation protocols with and without autonomic blockade or stimulation. To determine if selected anatomical indices are consistent with an autonomic imbalance, (123)I-labeled metaiodobenzylguanidine scintigraphy and immunocytochemical localization of tyrosine hydroxylase will be used to compare the sympathetic innervation of affected and unaffected dogs. We anticipate that this colony of German Shepherd dogs with a propensity for spontaneous ventricular arrhythmias and sudden death during sleep will serve as an unprovoked animal model of SIDS.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD028938-05
Application #
2201430
Study Section
Special Emphasis Panel (SRC (SI))
Project Start
1991-09-30
Project End
1998-08-31
Budget Start
1995-09-01
Budget End
1998-08-31
Support Year
5
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Cornell University
Department
Other Clinical Sciences
Type
Schools of Veterinary Medicine
DUNS #
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Pacioretty, L M; Cooper, B J; Gilmour Jr, R F (1994) Reduction of the transient outward potassium current in canine X-linked muscular dystrophy. Circulation 90:1350-6
Moise, N S; Meyers-Wallen, V; Flahive, W J et al. (1994) Inherited ventricular arrhythmias and sudden death in German shepherd dogs. J Am Coll Cardiol 24:233-43