Abstract 18659: Electrical Stimulation of the Intact Right Cervical Vago-Sympathetic Trunk Decreases Myocardial Norepinehrine Spillover in the Setting of Sympathetic Activation
Introduction: Cervical vagus nerve electrical stimulation (VNS) has been shown to improve functional indices in the setting of heart failure with depressed parasympathetic control. However, the cervical vagus nerve trunk contains sympathetic fibers which upon stimulation could paradoxically increase cardiac sympathetic drive and negatively affect the effects of VNS. This study assessed the cardiac hemodynamic/catecholamines effects of acute cervical intact-nerve VNS in vivo.
Methods: Ten beagle dogs (10.2 ± 0.7 kg) were anesthetized/instrumented with a clinically-applicable right-cervical VNS stimulation cuff/system. The effects of acute VNS stimulation (4 - 8 mA) on systemic/left-ventricular (LV) hemodynamics, and systemic/coronary sinus norepinephrine (NE) levels/spillover were assessed both under control conditions and compensatory cardiac sympathetic stimulation during induced hypotension (SNP, 2-5 ug/kg/min IV).
Results: Under control conditions, acute VNS triggered small dose-dependent increases in both systemic pressures (e.g., 9 ± 2% at 4mA) and arterial NE levels (e.g., 111.8 ± 16.3 at 8mA vs. 66.5 ± 10.0 pg/mL). However, VNS had negligible effects in both heart rate (HR: -1 ± 4% at 8mA) and myocardial NE spillover (11.4 ± 21.0 at 8mA vs. 31.0 ± 15.2 pg/mL), suggesting that VNS did not have a direct cardiac sympathetic effect. SNP decreased systemic pressures (97 ± 6 to 65 ± 5 mmHg), while increasing HR (87 ± 9 to 141 ± 10 bpm), estimated LV contractility (+86 ± 16%), and myocardial NE spillover (20.9 ± 11.4 to 70.3 ± 17.8 pg/mL), in line with an elevated cardiac sympathetic drive. In this setting, acute VNS markedly decreased cardiac NE spillover (-174 ± 62%, to -15.2 ± 20.2 pg/mL) and HR (-26 ± 5%, to 111 ± 7 bpm), while preserving systemic/LV hemodynamics. VNS also improved indices of LV relaxation under both control and enhanced sympathetic drive conditions (e.g., dP/dtmin: +20 ±10% and tau: -28 ± 4%).
Conclusions: Clinically-applicable acute electrical stimulation of the intact right-cervical vagus nerve not only does not enhance cardiac sympathetic drive but promotes ventricular relaxation and decreases cardiac NE spillover in the setting of sympathetic activation, thereby providing cardioprotection without adverse off target actions.
Author Disclosures: C.L. del Rio: Research Grant; Significant; Medtronic. G.E. Geist: None. B.L. Youngblood: None. E. Ferris: None. Y. Ueyama: None. M. Cismowski: None. G.E. Billman: Research Grant; Significant; Medtronic. P.J. Schwartz: Research Grant; Significant; Medtronic.
- © 2016 by American Heart Association, Inc.