Abstract 19667: Vagus Nerve Stimulation Normalizes Autonomic Neural Processing and Reduces Cardiac Hypertrophy in a Canine Model of Preserved Ejection Fraction Heart Failure
Objective: To determine whether vagus nerve stimulation (VNS) influences hypertensive-induced changes in cardiac function.
Methods: A model of preserved ejection fraction heart failure (HFpEF) was created in adult canines (n=23) via bilateral, non-restrictive renal wrapping (RW) with woven silk pouches. Cardiac echocardiographic and hemodynamic responses were measured longitudinally over 35±1 weeks. Nine animals were untreated; 14 animals received VNS implants (10 right- and 4 left-sided). VNS was initiated at 19±2 weeks of RW by systematically titrating over a 2 week period to an optimal intensity based on real-time measurement of heart rate dynamics [10 Hz, 2.5±0.2 mA, 250 μs pulse width, 22% duty cycle (18 s-ON, 66 s-OFF, continuously-cyclic)]. At termination, after 3 months of VNS therapy, hemodynamic profile and the evoked cardiac responses to stimulation of autonomic inputs (sympathetic and parasympathetic) to the heart were determined.
Results: The hemodynamic responses to the RW procedure (mean blood pressure and heart rate) primarily manifested in the first two months (107±5 baseline to 135±6 mmHg, p<0.004; 119±4 baseline to 119±3 beats/min, NS). Echocardiography revealed that RW was associated with a 36.2±9.1% increase in left ventricular (LV) mass (123±7 to 168±16 g, p<0.001), whereas VNS was associated with -12.7±3.5% regression of LV mass over the 3-month VNS treatment period (144±11 g, p<0.025). The evoked inotropic and lusitropic responses to direct stellate stimulation were enhanced in the RW-VNS group compared to the untreated group (Panel A), suggesting VNS restored cardiovascular features of autonomic control. Chronic RW exaggerated heart rate (Panel B) responses to varying levels of acute right cervical VNS (RCV). This behavior was mitigated by chronic VNS.
Conclusions: Chronic RCV, titrated to appropriate intensity, targets peripheral aspects of the cardiac nervous system to obtund adverse LV remodeling in a canine model of HFpEF.
Author Disclosures: J.L. Ardell: Research Grant; Significant; LivaNova PLC. Consultant/Advisory Board; Significant; LivaNova PLC. E. Southerland: None. E. Beaumont: None. R.W. Chui: None. P.S. Rajendran: None. S.D. Girouard: Consultant/Advisory Board; Modest; LivaNova PLC. B.H. KenKnight: Employment; Significant; LivaNova PLC. J. Armour: Consultant/Advisory Board; Significant; LivaNova PLC.
- © 2016 by American Heart Association, Inc.