Optimal Titration Is Important to Maximize the Beneficial Effects of Vagal Nerve Stimulation in Chronic Heart Failure.

ABSTRACT

BACKGROUND: Although vagal nerve stimulation (VNS) benefits patients with chronic heart failure (CHF), the optimal dose of VNS remains unknown. In clinical trials, adverse symptoms limited up-titration. In this study, we evaluated the impact of various voltages of VNS which were titrated below symptom threshold on cardiac function and CHF parameters in rat myocardial infarction (MI) models. METHODS AND RESULTS: We randomly allocated MI rats to vagal (VNS; n = 41) and sham (Sham; n = 16) stimulation groups. We stimulated the right vagal nerve with 20 Hz at 3 different voltages for 4 weeks. We defined Max as the highest voltage that did not evoke any symptom, Half as one-half of Max, and Quarter as one-fourth of Max. All 3 VNS groups significantly reduced biventricular weight compared with Sham (P < .05). In contrast, only Half decreased left ventricular (LV) end-diastolic pressure (Half 17.5 ± 2.0 mm Hg; Sham 24.2 ± 1.2 mm Hg; P < .05) and increased LV ejection fraction (Half 37.9 ± 3.1%; Sham 28.4 ± 2.3%,-P < .05) and LV maximum +dP/dt (Half 5918.6 ± 2.0 mm/Hg/s; Sham 5001.2 ± 563.2 mm Hg/s; P < .05). The number of large vagal nerve fibers was reduced with Max (Max 163.1 ± 43.0 counts/bundle; Sham 360.0 ±61.6 counts/bundle; P < .05), indicating significant neural damage by VNS. CONCLUSION: The optimal titration of VNS would maximize benefits for CHF and minimize adverse effects.