Stimulation Along the Vagal Pre and Postganglionic Pathway to Selectively Enhance Vagal Tone to the Heart

Objectives: Sympathetic overactivity and vagal withdrawal are cardinal presentations in patients with heart failure that predisposes them to malignant arrhythmias and sudden cardiac death. To develop therapy to enhance vagal tone and regain autonomic balance we conducted stimulation recruitment tests at three locations along the cardiac vagal pathway. Materials and Methodology: In anesthetized canines, small electrodes were placed against the vagus nerve (n=4) or in epicardial fat containing the sinoatrial or ventricular cardiac ganglia (n=8). Results: Stimulation of the vagus nerve induced vocal cord evoked potentials at 0.5 mA and increases in heart rate at 1.3 ± 0.3 mA. Higher currents were needed to induce parasympathetic effects of decreased heart rate and blood pressure, 3.7 ± 1.0 mA. Stimulation of the sinoatrial node ganglia decreased heart rate at a threshold current of 4.4 ± 2.1 mA. Stimulation of the ventricular ganglia, produced sympathetic effects at 9.3 ± 0.7 mA of current and ventricular arrhythmias or pacing at 10.7 ± 0.7 mA; using small wire electrodes unwanted sympathetic and ventricular pacing effects occurred at even lower stimulating currents. Conclusion: Our results show that the effects of stimulation are highly dependent upon the site of stimulation and stimulation currents. Further, given the significant side effects of whole nerve stimulation an important need exists for more selective vagal and cardiac ganglia stimulation technology as offered by microelectrode arrays.