Hydrogen sulfide and Serotonin in sleep apnea syndrome

• Project/Area Number: 16K09219
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Legal medicine
• Research Institution: Aichi Medical University
• Principal Investigator: HIRAI SHUICHI 愛知医科大学, 医学部, 特任教授 (70516054)
• Co-Investigator(Kenkyū-buntansha): 吉田 謙一 東京医科大学, 医学部, 主任教授 (40166947) ; 前田 秀将 東京医科大学, 医学部, 講師 (60407963) ; 畑山 直之 愛知医科大学, 医学部, 講師 (80534792)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 睡眠時無呼吸症候群 / 低酸素 / 呼吸中枢 / 睡眠時無呼吸 / 間歇的低酸素 / 間歇低酸素 / 硫化水素 / セロトニン

Outline of Final Research Achievements

The intermittent hypoxic exposure of the awake (under conscious) experimental animals has been analyzed as experimental animal models of obstructive sleep apnea syndrome. However rapid respiratory failure due to tongue root depression is occurred in actual cases of obstructive sleep apnea syndrome. Therefore, it is expected that it is different condition from obstructive sleep apnea syndrome. In this study, it became clear that intermittent obstructive respiratory failure and intermittent hypoxic exposure under anesthesia (unconsciousness) are different pathologies. In addition, we clarified that the occlusion time, not the number of occlusions, is related to the deterioration of the pathological condition.

Academic Significance and Societal Importance of the Research Achievements

閉塞型睡眠時無呼吸症候群は、舌根沈下などにより睡眠時の呼吸が停止することを繰り返すことで、良好な睡眠の妨げ、日中傾眠を誘発する。その結果、交通事故・災害事故・社会生活や家族問題を引き起こすなど、社会的問題になっている。本研究にて、新たに、閉塞型睡眠時無呼吸症候群の臨床病態を反映した実験動物モデルを確立したことにより、今後、診断、治療への応用研究が加速すると予想される。

Research Products

• [Journal Article] Improvement in Outcomes After Cardiac Arrest and Resuscitation by Inhibition of S-Nitrosoglutathione Reductase. (2019)
  • Author(s): Hayashida K, Bagchi A, Miyazaki Y, Hirai S, Seth D, Silverman MG, Rezoagli E, Marutani E, Mori N, Magliocca A, Liu X, Berra L, Hindle AG, Donnino MW, Malhotra R, Bradley MO, Stamler JS, Ichinose F.
  • Journal Title: Circulation Volume: 139 Issue: 6 Pages: 815-827
  • DOI: 10.1161/circulationaha.117.032488
  • Peer Reviewed
• [Journal Article] Breathing hydrogen sulfide prevents delayed paraplegia in mice. (2019)
  • Author(s): Kakinohana M, Marutani E, Tokuda K, Kida K, Kosugi S, Kasamatsu S, Magliocca A, Ikeda K, Kai S, Sakaguchi M, Hirai S, Xian M, Kaneki M, Ichinose F.
  • Journal Title: Free Radic Biol Med Volume: 131 Pages: 243-250
  • DOI: 10.1016/j.freeradbiomed.2018.12.003
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Preservation of rat limbs by hyperbaric carbon monoxide and oxygen (2018)
  • Author(s): Hatayama Naoyuki、Hirai Shuichi、Naito Munekazu、Terayama Hayato、Araki Jun、Yokota Hiroki、Matsushita Masayuki、Li Xiao-Kang、Itoh Masahiro
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 6627-6627
  • DOI: 10.1038/s41598-018-25070-y
  • Peer Reviewed / Open Access
• [Journal Article] Morphological study of the neurovascular bundle to elucidate nerve damage in pelvic surger (2016)
  • Author(s): Nishimura M, Nishizawa Y, Naito M, Hirai S, Itoh M, Ito M, Akamoto S, Suzuki Y
  • Journal Title: Int J Colorectal Dis. Volume: 31(3) Issue: 3 Pages: 503-9
  • DOI: 10.1007/s00384-015-2470-9
  • Peer Reviewed
• [Journal Article] Thiamine as a neuroprotective agent after cardiac arrest. (2016)
  • Author(s): Ikeda K, Liu X, Kida K, Marutani E, Hirai S, Sakaguchi M, Andersen LW, Bagchi A, Cocchi MN, Berg KM, Ichinose F, Donnino MW.
  • Journal Title: Resuscitation Volume: 105 Pages: 138-44
  • DOI: 10.1016/j.resuscitation.2016.04.024
  • Peer Reviewed
• [Journal Article] Functional evaluation of rat hearts transplanted after preservation in a high-pressure gaseous mixture of carbon monoxide and oxygen. (2016)
  • Author(s): Hatayama N, Inubushi M, Naito M, Hirai S, Jin YN, Tsuji AB, Seki K, Itoh M, Saga T, Li XK.．
  • Journal Title: Sci Rep. Volume: 6 Issue: 1 Pages: 32120-32120
  • DOI: 10.1038/srep32120
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Specific autoantigens identified by sera obtained from mice that are immunized with testicular germ cells alone. (2016)
  • Author(s): Terayama H, Hirai S, Naito M, Qu N, Katagiri C, Nagahori K, Hayashi S, Sasaki H, Moriya S, Hiramoto M, Miyazawa K, Hatayama N, Li ZL, Sakabe K, Matsushita M, Itoh M.
  • Journal Title: Sci Rep. Volume: 18 Issue: 1 Pages: 35599-35599
  • DOI: 10.1038/srep35599
  • Peer Reviewed / Open Access
• [Presentation] 閉塞性睡眠時無呼吸症候群病態解析のための無意識下間歇的気道閉塞モデルの確立. (2018)
  • Author(s): 加藤佑啓, 梅本佳納榮, 大矢祐輔, 畑山直之, 平井宗一, 内藤宗和, 中野隆.
  • Organizer: 123回日本解剖学会総会・全国学術集会．2018.
• [Presentation] 高圧ガスを用いた新たな移植臓器の保存方法. (2018)
  • Author(s): 畑山直之, 平井宗一, 横田紘季, 矢倉富子, 福重香, 中野隆, 内藤宗和.
  • Organizer: 第123回日本解剖学会総会・全国学術集会．2018.
• [Presentation] 閉塞性睡眠時無呼吸症候群病態解析のための無意識下間歇的気道閉塞モデルの確立 (2018)
  • Author(s): 加藤佑哲，梅本佳納榮，大矢祐輔，畑山直之，平井宗一，内藤宗和，中野隆
  • Organizer: 第123回日本解剖学会総会・全国学術集会
• [Patent(Industrial Property Rights)] 組成物，甘味付与組成物，風味改善組成物，微小気泡を含む対象物の製造方法，甘味付与方法，風味改善方法，飲食品，および飲食品の製造方法. (2018)
  • Inventor(s): 畑山直之, 内藤宗和, 平井宗一, 坂上茂樹.
  • Industrial Property Rights Holder: 畑山直之, 内藤宗和, 平井宗一, 坂上茂樹.
  • Industrial Property Rights Type: 特許
  • Filing Date: 2018
• [Patent(Industrial Property Rights)] 生体材料保存組成物，生体材料の保存方法，生体材料の生産方法，移植材料，および移植方法 (2018)
  • Inventor(s): 畑山直之, 内藤宗和, 平井宗一, 坂上茂樹.
  • Industrial Property Rights Holder: 畑山直之, 内藤宗和, 平井宗一, 坂上茂樹.
  • Industrial Property Rights Type: 特許
  • Filing Date: 2018
• [Patent(Industrial Property Rights)] 組成物，細胞保存組成物，細胞培養組成物，細胞製剤，微小気泡を含む対象物の製造方法，細胞の保存方法，細胞の培養方法，および細胞製剤の製造方法 (2018)
  • Inventor(s): 畑山直之, 内藤宗和, 平井宗一, 坂上茂樹.
  • Industrial Property Rights Holder: 畑山直之, 内藤宗和, 平井宗一, 坂上茂樹.
  • Industrial Property Rights Type: 特許
  • Filing Date: 2018