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

Akiko Nishizaki, Kazuo Sakamoto, Keita Saku, Kazuya Hosokawa, Takafumi Sakamoto, Yasuhiro Oga, Takuya Akashi, Yoshinori Murayama, Takuya Kishi, Tomomi Ide, Kenji Sunagawa

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16 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)631-638
Number of pages8
JournalJournal of Cardiac Failure
Issue number8
Publication statusPublished - Aug 1 2016

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine


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