Published Online
on September 22, 2009

A more recent version of this article appeared on November 1, 2009

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Original Article

Chronic Vagus Nerve Stimulation Improves Autonomic Control and Attenuates Systemic Inflammation and Heart Failure Progression in a Canine High Rate Pacing Model

Youhua Zhang^1,4; Zoran B. Popovic¹; Steve Bibevski²; Itaf Fakhry³; Domenic A. Sica³; David R. Van Wagoner¹ and Todor N. Mazgalev¹

¹ Cleveland Clinic, Cleveland, OH;
² University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH;
³ Virginia Commonwealth University, Richmond, VA

^* Corresponding author; email: zhangy2{at}ccf.org

Background—Autonomic dysfunction, characterized by sympathetic activation and vagal withdrawal, contributes to the progression of heart failure (HF). Although the therapeutic benefits of sympathetic inhibition with â-blockers in HF are clear, the role of increased vagal tone in this setting has been less studied. We have investigated the impact of enhancing vagal tone (achieved via chronic cervical vagus nerve stimulation, VNS) on HF development in a canine high-rate ventricular pacing model.

Methods and Results—Fifteen dogs were randomized into control (n=7) and VNS (n=8) groups. All dogs underwent 8 weeks of high-rate ventricular pacing (at 220 bpm for the first 4 weeks to develop HF, and another 4 weeks at 180 bpm to maintain HF). Concomitant VNS, at an intensity reducing sinus rate about 20 bpm, was delivered together with the ventricular pacing in the VNS group. At 4 and 8 weeks of ventricular pacing, both left ventricular (LV) end diastolic (LVEDV) and systolic (LVESV) volumes were lower and LV ejection fraction (LVEF) was higher in the VNS group than in the control group. Heart rate variability and baroreflex sensitivity improved in the VNS dogs. Rises in plasma norepinephrine, angiotensin II and C-reactive protein levels, ordinarily expected in this model, were markedly attenuated with VNS treatment.

Conclusions—Chronic VNS improves cardiac autonomic control and significantly attenuates HF development in the canine high-rate ventricular pacing model. The therapeutic benefit of VNS is associated with pronounced anti-inflammatory effects. VNS is a novel and potentially useful therapy for treating HF.

Key Words: heart failure • nervous system, autonomic • vagus nerve • Vagus nerve stimulation