Vagus nerve stimulation improves left ventricular function in a canine model of chronic heart failure

Autonomic dysfunction is a feature of chronic heart failure (HF). This study tested the hypothesis that chronic open-loop electrical vagus nerve stimulation (VNS) improves LV structure and function in canines with chronic HF. Twenty-six canines with HF (EF 35) produced by intracoronary microembolizations were implanted with a bipolar cuff electrode around the right cervical vagus nerve and connected to an implantable pulse generator. The canines were enrolled in Control (n 7) vs. VNS therapy (n 7) or a crossover study, with crossovers occurring at 3 months (C VNS, n 6; VNS C, n 6). After 6 months of VNS, LVEF and LV end-systolic volume (ESV) were significantly improved compared with Control (EF Control 4.6 0.9 vs. VNS 6.0 1.6, P 0.001) and (ESV Control 8.3 1.8 mL vs. VNS 3.0 2.3 mL, P 0.002. Plasma and tissue biomarkers were also improved. In the crossover study, VNS also resulted in a significant improvement in EF and ESV compared with Control (EF Control 2.3 0.65 vs. VNS 6.7 1.1 mL, P 0.001 and ESV Control 3.2 1.2 mL vs. VNS 4.0 0.9 mL, P 0.001). Initiation of therapy in the Control group at 3 months resulted in a significant improvement in EF (Control 4.7 1.4 vs. VNS 3.7 0.74, P 0.001) and ESV (Control 1.5 1.2 mL vs. NS 5.5 1.6 mL, P 0.003) by 6 months. In canines with HF, long-term, open-looped low levels of VNS therapy improves LV systolic function, prevents progressive LV enlargement, and improves biomarkers of HF when compared with control animals that did not receive therapy.