Abstract 15772: Chronotropic Responses to Low-Amplitude Autonomic Regulation Therapy Are Unaffected by Ace Inhibition as Well as Beta Adrenergic and Funny Channel Blockade

Background: Chronic, intermittent right vagus nerve stimulation (VNS) imparts cardioprotective effects in animals and humans with heart failure. However, the cardiac effects of chronic VNS in the presence of pharmaceutical agents that modulate autonomic and cardiac function are not understood. Methods: Normal canines (n=4) were implanted with VNS therapy systems on the right cervical vagus (RCV) nerve and placed on medical therapy, either individually or in combination. During successive 2-week phases, animals were administered twice daily (PO) a: i) beta blocker (metoprolol, 12.25 mg); ii) ACE inhibitor (enalapril, 2.5 mg); iii) funny channel blocker (ivabradine, 5.0 mg); iv) metoprolol + enalapril; or v) metoprolol + enalapril + Ivabradine. In conscious animals, chronotropic responses to recurring cycles of 10 Hz RCV VNS (14-s ON-time, 48-s OFF-time) were measured at the end of each 2-week therapy phase and compared to baseline. Chronotropic responses to RCV VNS were then compared to acute treatment wit...