Controlled intermittent asystole cardiac therapy induced by pharmacologically potentiated vagus nerve stimulation in normal and hibernating myocardium

Background Pharmacologically potentiated electrical stimulation of the right vagus nerve achieves controlled intermittent asystole cardiac therapy. The present study examined pathophysiologic consequences of repetitive intermittent asystoles on contractile function, myocardial blood flow, and vagus nerve function and morphology. Methods Open-chest anesthetized canines, with either normal left anterior descending (LAD) coronary arteries (n = 8) or severely stenotic LADs (n = 8), received pharmacologic pretreatment with pyridostigmine (0.5 mg/kg), propranolol (80 μg/kg), and verapamil (50 μg/kg) before vagus nerve stimulation. Time-matched control animals with normal (n = 4) or severely stenotic LADs (n = 6) received drugs but no vagus nerve stimulation. The vagus nerve was stimulated for 12 seconds (“on”) and rested for 15 seconds (“off”). This algorithm was repeated for 15 on-off cycles, simulating using controlled intermittent asystole during the placement of 15 sutures in a distal coronary anastomosis. This 15-cycle sequence was repeated twice more, simulating a three-vessel bypass. Results Normal coronary arteries: Ninety minutes after three sets of controlled intermittent asystole, LAD blood flow was unchanged from base line (36.6 ± 4.5 versus 33.0 ± 4.2 mL/min, p = 0.4), and global left ventricular performance (impedance catheter, end-systolic pressure-volume relations) was similar to baseline (7.4 ± 1.2 versus7.2 ± 1.0 mm Hg/mL, p = 0.1). Left anterior descending coronary artery stenosis model: Ninety minutes after CIA, there were no significant differences versus control animals in regional LAD blood flow (27 ± 4 versus 29 ± 5 mL/min, p = 0.4) or fractional shortening of LAD myocardium (sonomicrometry; 6.2% ± 1.8% versus 5.4% ± 1.2%, p = 0.1). Vagus nerve conduction and morphology were unchanged from baseline. Conclusions Repetitive controlled intermittent asystole does not impair poststimulation coronary blood flow, cardiac contractile function, or vagus nerve function. Controlled intermittent asystole may be useful to facilitate off-pump or endoscopic coronary artery bypass grafting.