Investigation of the relationship of baroreflex failure and worsening heart failure

• Project/Area Number: 26860569
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Kyushu University
• Principal Investigator: Sakamoto Takafumi 九州大学, 大学病院, その他 (50641015)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: baroreflex / heart failure / hemodynamics / pulmonary edema / HFpEF / circulatory equilibrium / 動脈圧反射 / 血圧制御 / 自律神経制御 / 心機能 / 血行動態 / 心不全 / 循環平衡

Outline of Final Research Achievements

We defined the dynamic characteristics of the baroreflex (BR) regulation of the ventricular and vascular properties using the white noise method. Based on the concept of the ventriculo-arterial coupling and the framework of circulatory equilibrium, we reported that vascular properties (especially in stressed blood volume), not ventricular properties, predominantly contribute to BR regulation of arterial pressure. Based on this result, we hypothesized that BR failure may cause volume intolerance.
We evaluated the volume tolerance by infusion of dextran while measuring left atrial pressure, an index of pulmonary edema, in both normal BR and BR failure models. In BR failure, small amount of dextran led to marked increase of left atrial pressure suggesting that the BR failure is one of the main mechanism of flash pulmonary edema. This result may lead us to develop a new therapeutic strategy to treat heart failure with preserved ejection fraction.

Research Products

• [Journal Article] Changes in Vascular Properties, Not Ventricular Properties, Predominantly Contribute to Baroreflex Regulation of Arterial Pressure. (2015)
  • Author(s): Sakamoto T, Kakino T, Sakamoto K, Tobushi T, Tanaka A, Saku K, Hosokawa K, Onitsuka K, Murayama Y, Tsutsumi T, Ide T, Sunagawa K.
  • Journal Title: Am J Physiol Heart Circ Physiol. Volume: 308 Issue: 1 Pages: H49-H58
  • DOI: 10.1152/ajpheart.00552.2014
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Afferent vagal nerve stimulation resets baroreflex neural arc and inhibits sympathetic nerve activity. (2014)
  • Author(s): Saku K, Kishi T, Sakamoto K, Hosokawa K, Sakamoto T, Murayama Y, Kakino T, Ikeda M, Ide T, Sunagawa K.
  • Journal Title: Physiol Rep. Volume: 2 Issue: 9 Pages: e12136-e12136
  • DOI: 10.14814/phy2.12136
  • Peer Reviewed / Open Access
• [Presentation] 1.重症心不全における自律神経系の意義とその治療対象としての可能性 (2015)
  • Author(s): 坂本隆史
  • Organizer: 第53回日本人工臓器学会
  • Place of Presentation: 東京
  • Year and Date: 2015-11-21
• [Presentation] 2.Autonomic Regulation of the Pressure-Volume Relationship and Hemodynamics in Normal and Heart Failure (2015)
  • Author(s): Sakamoto T et al
  • Organizer: 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society
  • Place of Presentation: Millano
  • Year and Date: 2015-08-25
  • Int'l Joint Research
• [Presentation] 慢性心不全に対する神経介入治療の現状と期待 (2015)
  • Author(s): 坂本隆史
  • Organizer: 第1回J-ISCP学術集会
  • Place of Presentation: 京都
  • Year and Date: 2015-06-20
• [Presentation] 4.Baroreflex activation therapy (BAT) as a novel therapeutic strategy for acute decompensated heart failure with reduced ejection fraction (2015)
  • Author(s): Sakamoto T et al
  • Organizer: The 79th Annual Scientific Meeting of The Japanese Circulation Society
  • Place of Presentation: 大阪
  • Year and Date: 2015-04-25
• [Presentation] Discordant Impact of Baroreflex Activation on Cardiac Output Between the Normal Heart and Failing Heart (2014)
  • Author(s): Sakamoto T, Kakino T, Saku K, Sakamoto K, Sunagawa K.
  • Organizer: The 87th Annual Scientific Meeting of the American Heart Association
  • Place of Presentation: Chicago, USA,
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] Activation of baroreflex instantly reduces left atrial pressure and increases cardiac output in dogs with pacing induced heart failure (2014)
  • Author(s): Sakamoto T, Kakino T, Saku K, Sunagawa K.
  • Organizer: 第18回日本心不全学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2014-10-10 – 2014-10-12
• [Presentation] Intravascular electrical stimulation of carotid sinus activates baroreflex and decreases arterial pressure in an anesthetized dog (2014)
  • Author(s): Sakamoto T, Saku K, Kakino T, Arimura T, Sunagawa K.
  • Organizer: 第53回日本生体医工学会大会
  • Place of Presentation: 仙台
  • Year and Date: 2014-06-24 – 2014-06-26