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

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