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 with high dose metoprolol (1 mg/kg) and cholinergic blockade (Glycopyrrolate, .4 mg/kg).
Results: Compared to baseline, basal heart rate was minimally affected by low level beta blockade, ACE inhibition and or funny channel blockade. High dose beta blocker reduced heart rate by 15%. Very low amplitude VNS (0.25-1.25 mA) imposed subtle changes in HR and HR variability, indicating autonomic engagement. At moderate amplitudes (1.5-3.5 mAmp), VNS reduced heart rate during the on phase up to 25%. As compared to baseline, there was no significant difference in heart rate response to RCV VNS in the presence of any combination of chronic medical therapy. Chronic drug therapy likewise exerted no effects on heart rate in the VNS off phase. Conversely, acute treatment with Glycopyrrolate mitigated the bradycardia evoked by RCV VNS.
Conclusions: VNS induced chronotropic responses are dependent on stimulation amplitude, pulse width, and frequency. Chronic autonomic regulation therapy is well tolerated, both alone and in the presence of heart failure drugs. RCV VNS evoked chronotropic responses are not altered by the presence of such heart failure drug therapy.
- © 2013 by American Heart Association, Inc.