Abstract
AIMS: 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. METHODS AND RESULTS: 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 (ΔEF Control -4.6 ± 0.9% vs. VNS 6.0 ± 1.6%, P < 0.001) and (ΔESV 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 (ΔEF Control -2.3 ± 0.65% vs. VNS 6.7 ± 1.1 mL, P < 0.001 and ΔESV 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. CONCLUSIONS: 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.