title: 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.
  
  
  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.
  
  
  CONCLUSIONS
  The optimal titration of VNS would maximize benefits for CHF and minimize adverse effects.
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan. Electronic address: nishizak@cardiol.med.kyushu-u.ac.jp.
authors.forename: Akiko
authors.initials: A
authors.lastname: Nishizaki
authors.affiliation: Department of Cardiovascular Medicine, Saiseikai General Hospital, Fukuoka, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Sakamoto
authors.affiliation: Department of Therapeutic Regulation of Cardiovascular Homeostasis, Center for Disruptive Cardiovascular Medicine, Kyushu University, Fukuoka, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Saku
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Hosokawa
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Sakamoto
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Oga
authors.affiliation: Department of Therapeutic Regulation of Cardiovascular Homeostasis, Center for Disruptive Cardiovascular Medicine, Kyushu University, Fukuoka, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Akashi
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Murayama
authors.affiliation: Department of Therapeutic Regulation of Cardiovascular Homeostasis, Center for Disruptive Cardiovascular Medicine, Kyushu University, Fukuoka, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Kishi
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Ide
authors.affiliation: Department of Therapeutic Regulation of Cardiovascular Homeostasis, Center for Disruptive Cardiovascular Medicine, Kyushu University, Fukuoka, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sunagawa
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006333:Heart Failure / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D055536:Vagus Nerve Stimulation / Q000379:methods*; D016277:Ventricular Function, Left / Q000502:physiology*; D020257:Ventricular Remodeling
keywords: Chronic heart failure; Myocardial infarction; Vagal nerve stimulation