title: Striking volume intolerance is induced by mimicking arterial baroreflex failure in normal left ventricular function.
abstract: BACKGROUND
  Patients with heart failure and preserved ejection fraction (HFpEF) are supersensitive to volume overload, and a striking increase in left atrial pressure (LAP) often occurs transiently and is rapidly resolved by intravascular volume reduction. The arterial baroreflex is a powerful regulator of intravascular stressed blood volume. We examined whether arterial baroreflex failure (FAIL) mimicked by constant carotid sinus pressure (CSP) causes a striking increase in LAP and systemic arterial pressure (AP) by volume loading in rats with normal left ventricular (LV) function.
  
  
  RESULTS
  In anesthetized Sprague-Dawley rats, we isolated bilateral carotid sinuses and controlled CSP by a servo-controlled piston pump. We mimicked the normal arterial baroreflex by matching CSP to instantaneous AP and FAIL by maintaining CSP at a constant value regardless of AP. We infused dextran stepwise (infused volume [Vi]) until LAP reached 15 mm Hg and obtained the LAP-Vi relationship. We estimated the critical Vi as the Vi at which LAP reached 20 mm Hg. In FAIL, critical Vi decreased markedly from 19.4 ± 1.6 mL/kg to 15.6 ± 1.6 mL/kg (P < .01), whereas AP at the critical Vi increased (194 ± 6 mm Hg vs 163 ± 6 mm Hg; P < .01). We demonstrated that an artificial arterial baroreflex system we recently developed could fully restore the physiologic volume intolerance in the absence of native arterial baroreflex.
  
  
  CONCLUSIONS
  Arterial baroreflex failure induces striking volume intolerance in the absence of LV dysfunction and may play an important role in the pathogenesis of acute heart failure, especially in states of HFpEF.
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Kouta
authors.initials: K
authors.lastname: Funakoshi
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 Advanced Therapeutics for Cardiovascular Diseases, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan. Electronic address: tkishi@cardiol.med.kyushu-u.ac.jp.
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 Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sunagawa
mesh_terms: D000208:Acute Disease; D000818:Animals; D017704:Baroreflex / Q000502:physiology*; D001794:Blood Pressure; D001810:Blood Volume; D004195:Disease Models, Animal; D006333:Heart Failure / Q000503:physiopathology*; D008297:Male; D008955:Models, Cardiovascular; D011311:Pressoreceptors / Q000502:physiology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013318:Stroke Volume / Q000502:physiology*; D014655:Vascular Resistance / Q000502:physiology
keywords: Heart failure; arterial baroreflex; volume intolerance