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PRECLINICAL INVESTIGATION

Long-term subthreshold electrical stimulation of the left stellate ganglion and a canine model of sudden cardiac death

Moshe Swissa, MD^*, Shengmei Zhou, MD^*, Ignacio Gonzalez-Gomez, MD, Che-Ming Chang, MD^*, Angela C. Lai, BA^*, Adam W. Cates, PhD, Michael C. Fishbein, MD, Hrayr S. Karagueuzian, PhD^*, Peng-Sheng Chen, MD^* and Lan S. Chen, MD^,*

^* Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA
Guidant Corporation, St. Paul, Minnesota, USA
Department of Pathology and Laboratory Medicine, Geffen School of Medicine, University of California, Los Angeles, USA
Children's Hospital of Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, California, USA

Manuscript received December 18, 2002; revised manuscript received July 22, 2003, accepted July 22, 2003.

^* Reprint requests and correspondence: Dr. Lan S. Chen, Division of Neurology #82, Children's Hospital of Los Angeles, 4650 Sunset Boulevard, Los Angeles, California 90027, USA.
lchen{at}chla.usc.edu

OBJECTIVES: We sought to develop a high-yield canine model of sudden cardiac death (SCD).

BACKGROUND: Because electrical stimulation is a powerful means to elicit nerve sprouting, we hypothesize that subthreshold electrical stimulation is more effective than nerve growth factor (NGF) infusion in inducing nerve sprouting and SCD in dogs with myocardial infarction (MI) and complete atrioventricular block (CAVB).

METHODS: We gave subthreshold electrical stimulation to the left stellate ganglion (LSG) in six normal dogs for 41 ± 9 days (protocol 1) and to six dogs with MI and CAVB for 41 ± 29 days, while continuously monitoring their cardiac rhythm (protocol 2). We also monitored the rhythm of two dogs with MI, CAVB, and NGF infusion to the LSG and determined the ventricular nerve density in six healthy control dogs.

RESULTS: In protocol 1, the hearts from dogs with LSG electrical stimulation had a higher density of nerve fibers immunopositive to tyrosine hydroxylase, synaptophysin, and growth-associated protein-43 than those of normal control dogs (p < 0.01). In protocol 2, there was a high magnitude of cardiac nerve sprouting in all dogs studied. Ventricular tachycardia 8 beats and 20 beats was more frequent in dogs with electrical stimulation than in dogs with NGF infusion to the LSG (36 ± 60 and 11 ± 17 vs. 4.7 ± 6.1 and 0.1 ± 0.33 episodes per day, p < 0.05 and p < 0.03, respectively). Four of six dogs in protocol 2 had SCD.

CONCLUSIONS: Subthreshold electrical stimulation of the LSG induces cardiac nerve sprouting and sympathetic hyperinnervation and facilitates the development of a high-yield canine model of ventricular arrhythmia and SCD.

Abbreviations and Acronyms   CAVB = complete atrioventricular block   DSI = Data Sciences International   GAP43 = growth-associated protein-43   ICD = implantable cardioverter-defibrillator   LSG = left stellate ganglion   LTP = long-term potentiation   MI = myocardial infarction   NGF = nerve growth factor   SCD = sudden cardiac death   SYN = synaptophysin   TH = tyrosine hydroxylase   VT = ventricular tachycardia

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