急性心不全に対する補助循環治療成績を改善する新規グレリン皮下投与法の開発研究

2017 Fiscal Year Annual Research Report

• Project/Area Number: 16F16118
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: 巽 英介 国立研究開発法人国立循環器病研究センター, 研究所, 部長 (00216996)
• Co-Investigator(Kenkyū-buntansha): SUKUMARAN VIJAYAKUMAR 国立研究開発法人国立循環器病研究センター, 研究所, 外国人特別研究員
• Project Period (FY): 2016-04-22 – 2018-03-31
• Keywords: Ghrelin / inflammation / organ damage / oxidative stress / cardiopulmonary bypass

Outline of Annual Research Achievements

Cardiopulmonary bypass (CPB) induced inflammation significantly contributes to the development of postoperative complications, including respiratory failure, myocardial, renal and neurological dysfunction and ultimately leads to multiple organ failure. Ghrelin is a small endogenous peptide with wide ranging physiological effects on metabolism and cardiovascular regulation. We investigated the protective effects of ghrelin against the CPB-induced inflammatory reactions, oxidative stress and acute organ damage. Adult male rats were subjected to CPB for 4 hrs and randomly received vehicle (n=6) or a bolus of ghrelin (150 microgram/kg, sc, n=6). Rats were euthanized and heart, lung, liver, kidney and brain samples were harvested for histopathology. Blood samples were taken before CPB, after 2 hrs and 4 hrs of CPB. We measured the plasma levels of cytokines, catecholamines and organ damage markers and glutathione concentrations. CPB-induced leucocytosis with increased plasma levels of TNF-α, IL-6 indicating an inflammatory response. Our study results suggest that even though ghrelin only partially inhibited the large CPB induced increase in catecholamines and organ macrophage infiltration, it reduced oxidative stress and subsequent cell damage (Sukumaran et al., 2018). Administration of ghrelin might provide an effective co-treatment for reducing widespread CPB-induced organ injury.

Research Progress Status

29年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

29年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Ghrelin Pre-treatment Attenuates Local Oxidative Stress and End Organ Damage During Cardiopulmonary Bypass in Anesthetized Rats (2018)
  • Author(s): Sukumaran V, Tsuchimochi H, Fujii Y, Hosoda H, Kangawa K, Akiyama T, Shirai M, Tatsumi E, Pearson JT
  • Journal Title: Fronters in Physiology Volume: 9 Pages: Article 196
  • DOI: 10.3389/fphys.2018.00196
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Subcutaneous ghrelin administration reduces the oxidative stress and end-organ damage during cardiopulmonary bypass in a rat model (2018)
  • Author(s): Sukumaran V, Tsuchimochi H, Sonobe T, Shirai M, Tatsumi E, Pearson JT
  • Organizer: The 95th Annual Meeting of Physiological Society of Japan
• [Presentation] Liraglutide treatment improves renal vascular function in Zucker rats as visualized by microangiography (2017)
  • Author(s): Sukumaran V, Tsuchimochi H, Tatsumi E, Shirai M and Pearson JT
  • Organizer: ASN Kidney Week 2017, New Orleans, USA
  • Int'l Joint Research