Elucidation of the mechanism of ischemia/reperfusion injury of the lung and development of preventive and therapeutic maneuvers

• Project/Area Number: 17390481
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Emergency medicine
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: IMAI Takasuke Tokyo Medical and Dental University, 大学院・医歯学総合研究科, 教授 (60091964)
• Co-Investigator(Kenkyū-buntansha): 倉田 俊一 東京医科歯科大学, 難治疾患研究所, 准教授(遺伝生化学) (60140901) ; 江石 義信 東京医科歯科大学, 大学院・医歯学総合研究科, 教授(病理学) (70151959)
• Project Period (FY): 2005 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥12,760,000 (Direct Cost: ¥11,500,000、Indirect Cost: ¥1,260,000); Fiscal Year 2008: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2007: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2006: ¥2,700,000 (Direct Cost: ¥2,700,000); Fiscal Year 2005: ¥4,600,000 (Direct Cost: ¥4,600,000)
• Keywords: 移植 / 再生医療 / 細胞 / 組織 / 生理学 / 虚血再環流傷害 / 肺循環 / 移植・再生医療 / 細胞・組織 / 虚血再還流障害 / isolated perfused lung / ischemia reperfusion injury / tumor necrosis factor-α / TNF-α converting enzyme / lung-lung interaction / remote organ damage / 虚血・再還流障害 / 肺血管内皮細胞 / 血管内圧 / 炎症性サイトカイン / mRNA / RT-PCR / in situ hybridization / immunofluorecence

Research Abstract

片側肺を虚血、対側肺をコントロールとして用いることのできる遊離環流肺標本の確立、本モデルを用いて正常組織酸素、炭酸ガス分圧下で虚血傷害がoxygen radaicals, TNF-の産生により起こることを実証した。さらに、肺静脈圧を一定陽圧に保つことにより虚血傷害が阻止できることを見出した。また、虚血傷害により傷害肺からはTNF-, oxygen radicalsが放出されて、対側肺(遠隔臓器の代表)の透過性亢進を来すことを立証し、肺傷害による多臓器傷害発現機序の研究の端緒を開いた。

Research Products

• [Journal Article] TNF-α induction on respiratory epithelium in isolated, unilaterally hyperventilated rat lung (2009)
  • Author(s): Aishan Bilali, et al
  • Journal Title: 日本集中治療医学会雑誌 16
  • Peer Reviewed
• [Journal Article] Salavage of nonischemic control lung from injury by unilateral ischemic lung with apocynin, a nicotinamide adenine dinucleotide phosphate(NADPH)oxidase inhibitor, in isolated perfused rat lung (2008)
  • Author(s): Chenting Zhu, Aishan Bilali, Gabriela S Georgieva, Shunichi Kurata, Chieko Mitaka, Takasuke Imai
  • Journal Title: Translationa Research 152 Pages: 273-282
  • Peer Reviewed
• [Journal Article] Salavage of nonischemic control lung from injury by unilateral ischemic lung with apocynin, a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, in isolated perfused rat lung (2008)
  • Author(s): Chenting Zhu, et al
  • Journal Title: Translational Research 152 Pages: 273-282
  • Peer Reviewed
• [Journal Article] Unilateral ischemic lung induces contralateral lung injury by liberating mediators in circulation (2008)
  • Author(s): Gabriela S Georgieva, et al
  • Journal Title: 日本集中治療医学会雑誌 15
  • Peer Reviewed
• [Journal Article] Injury of CPAP lung by mediators from isolated perfused unilateral hyperventilated rat lung (2008)
  • Author(s): Bilali Aishan, et al
  • Journal Title: 日本集中治療医学会雑誌 15
  • Peer Reviewed
• [Journal Article] The effect of TNF-α on microvascular permeability in an isolated perfused lung (2008)
  • Author(s): Georgieva Gabriela S, et al
  • Journal Title: 日本集中治療医学会雑誌 15
  • Peer Reviewed
• [Journal Article] Induction of TNF-α on respiratory epithelium in unilateral hyperventilated lung an increased permeability by the recirculated perfusate in control lung maintained at CPAP (2.5 cmH20) in isolated, separately ventilated, perfused rat lung (2008)
  • Author(s): Aishan Bilali, et al
  • Journal Title: Crit Care Med 36
  • Peer Reviewed
• [Journal Article] Apaf-1-deficient fog mouse cell apoptosis involves hypo-polarization of the mitochondrial inner membrane, ATP depletion and citrate accumulation (2008)
  • Author(s): Iyoko Katoh, et al
  • Journal Title: Cell Res 18 Pages: 1210-1219
  • Peer Reviewed
• [Journal Article] Nonischemic lung injury by mediators from unilateral ischemic reperfused lung : ameliorating effect of tumor necrosis factor-α-converting enzyme inhibitor (2007)
  • Author(s): Gabriela S Georgieva, Shunichi Kurata, Satoshi Ikeda, Yoshinobu Eishi, Chieko Mitaka, Takasuke Imai
  • Journal Title: SHOCK 27 Pages: 84-90
  • Peer Reviewed
• [Journal Article] Nonischemic lung injury by mediators from unilateral ischemic reperfused lung: Ameliorating effect of tumor necrosis factor-α-converting enzyme inhibitor (2007)
  • Author(s): Gabriela S Georgieva, et. al.
  • Journal Title: SHOCK 27 Pages: 84-90
  • Peer Reviewed
• [Journal Article] Injury of CPAP lung by mediators from isolated perfused unilateral hyper ventilated rat lung (2007)
  • Author(s): Aishan Bilali, et. al.
  • Journal Title: Crit Care Med 35
  • Peer Reviewed
• [Journal Article] Ameliorating effect of combination of apocynin and TACEI on ischemia/reperfusion (I/R) injury (2007)
  • Author(s): Chenting Zhu, et. al.
  • Journal Title: 日本集中治療医学会雑誌 14
  • Peer Reviewed
• [Journal Article] Effect of positive (5 mmHg) pulmonary venous pressure on isolated ischemic-reperfused rat lungs maintained at CPAP (2007)
  • Author(s): Georgieva GS, et. al.
  • Journal Title: Intensive Care Med 33
  • Peer Reviewed
• [Journal Article] Induction of cytokine mRNA and edema in isolated perfused unilateral hyperventilated rat lung (2007)
  • Author(s): Bilali Aishan, et. al.
  • Journal Title: 日本集中治療医学会雑誌 14
  • Peer Reviewed
• [Journal Article] Nonischemic lung injury by mediators from unilateral ischemic reperfused lung : Ameliorating effect of tumor necrosis factor-α-converting enzyme inhibitor (2007)
  • Author(s): Gabriela S Georgieva, Shunichi Kurata, Satoshi Ikeda, Ypshinobu Eishi, Chieko Mitaka, Takasuke Imai
  • Journal Title: SHOCK 27 Pages: 84-90
• [Journal Article] Prevention of ischemia reperfusion injury by positive pulmonary venous pressure in isolated rat lung (2006)
  • Author(s): Gabriela S Georgieva, Shunichi Kurata, Satoshi Ikeda, Shu Teng, Iyoko Katoh, Yoshinobu Eishi, Chieko Mitaka, Takasuke Imai
  • Journal Title: SHOCK 25 Pages: 66-72
  • Peer Reviewed
• [Journal Article] Prevention of ishcmia reperfusion injury by positive pulmonary venous pressuree in isolated rat lung (2006)
  • Author(s): Gabriela S Georgieva, Shunichi Kurata, Satoshi Ikeda, Shu Teng, Iyoko Katoh, Yoshinobu Eishi, Chieko Mitaka, Takasuke Imai
  • Journal Title: SHOCK 25 Pages: 66-72
• [Journal Article] High tidal volume (TV) ventilation induced cytokine mRNA and edema in hyperventilated lung in isolated perfused unilateral hyperventilated lung (2006)
  • Author(s): Aishan Bilali, Chenting Zhu, Gabriela S Georgieva, Shunichi Kurata, Takasuke Imai
  • Journal Title: Crit Care Med 34
• [Journal Article] Ameliorating effect of combination of NADPH oxidase inhibitor (Apocynin) and TNF-α converting enzyme inhibitor (TACEI) on ischemia/reperfusion injury (2006)
  • Author(s): Chentin Zhu, Aishan Bilali, Gabriela S Georgieva, Shunichi Kurata, Takasuke Imai
  • Journal Title: Crit Care Med 34
• [Journal Article] Ventilated ischemic reperfused left lung (LL) increase inflammation in the contralateral right lung (2005)
  • Author(s): Gabriela S Georgieva
  • Journal Title: The 5^<th> Joint Scientific Congress of Korean-Japanese Intensivists, ABSTRACT Pages: 85-85
• [Journal Article] Tumor necrosis factor-alhpa converting enzyme inhibitor(TACEI)ameliorates control right lung (RL) injury by humor mediators liberate from unilateral ischemia/reperfused (I/R) left lung (LL) (2005)
  • Author(s): Gabriela S Georgieva
  • Journal Title: Crit Care Med 33
• [Journal Article] Ischemic reperfused left lung (LL) increases expression of inflammator cytokines mRNA in the control right lung (RL) (2005)
  • Author(s): Gabriela S Georgieva
  • Journal Title: 日本救急医学会雑誌 16 Pages: 430-430
• [Presentation] TNF-α induction on respiratory epithelium in isolated, unilaterally hyperventilated rat lung (2009)
  • Author(s): Aishan Bilali, Satoshi Ikeda, Shunichi Kurata, Takasuke Imai
  • Organizer: 第36回日本集中治療医学会学術集会
  • Place of Presentation: 大阪国際会議場、大阪
  • Year and Date: 2009-02-26
• [Presentation] Induction of TNF-α on respiratory epithelium in unilateral hyperventilated lung an increased permeability by the recirculated perfusate in control lung maintained at CPAP(2.5 cmH20)in isolated, separately ventilated, perfused rat lung (2009)
  • Author(s): Aisha Bilali, Chenting Zhu, Gabriela Georgieva, Shunichi Kurata, Satoshi Ikeda, Takasuke Imai
  • Organizer: 38^<th> Critical Care Congress
  • Place of Presentation: Gaylord Opryland Resort and Convention Center, Nahville, Tennessee, USA
  • Year and Date: 2009-02-01
• [Presentation] Induction of TNF-α on respiratory epithelium in unilateral hyperventilated lung an increased permeability by the recirculated perfusate in control lung maintained at CPAP (2.5 cmH20) in isolated, separately ventilated, perfused rat lung (2009)
  • Author(s): Aisha Bilali, et al
  • Organizer: 38^<th> critical Care Congress
  • Place of Presentation: Gaylord Opryland Resort and Convention Center Nashville, Tennessee
  • Year and Date: 2009-01-31
• [Presentation] Unilateral ischemic lung induces contralateral lung injury by liberating mdiators in cirulation Symposium "Acute Respiratory Failure and remote organ damage" (2008)
  • Author(s): Gabriela S Georgieva, Shunichi Kurata, Aisan Bilari, Chenting Zhu, Takasuke Imai
  • Organizer: 第35回日本集中治療医学会学術集会
  • Place of Presentation: 京王プラザホテル、東京
  • Year and Date: 2008-02-16
• [Presentation] Unilateral ischemic lung induces contralateral lung injury by liberating mediators in circulation (2008)
  • Author(s): Gabriela S Georgieva, Shunichi Kuata, Aisan Bilari, Chenting Zhu, Takasukelmai Takasuke
  • Organizer: 第35回日本集中治療医学会学術集会シンポジウム Acute Respiratory failure and remote organ damage
  • Place of Presentation: 東京新宿京王プラザホテル
  • Year and Date: 2008-02-16
• [Presentation] Injury of CPAP lung by mediators from isolated perfused unilateral hyperventilated rat lung (2008)
  • Author(s): Bilali Aishan, Zhu Chenting, Georgieva S Gabriela, Kurata Shunichi, Imai Takasuke
  • Organizer: 第35回日本集中治療医学会
  • Place of Presentation: 京王プラザホテル、東京
  • Year and Date: 2008-02-14
• [Presentation] The effect of TNF-α on microvascular permeability in an isolated perfused lung (2008)
  • Author(s): Georgieva Gabriela S, Kurata Shunichi, Bilali Aishan, Zhu Chengting, Imai Takasuke
  • Organizer: 第35回日本集中治療医学会
  • Place of Presentation: 京王プラザホテル、東京
  • Year and Date: 2008-02-14
• [Presentation] Injury of CPAP lung by mediators from isolated perfused unilateral hyperventilated rat lung (2008)
  • Author(s): Bilali Aishan, Zhu Chenting, Georgieva Gabriela S, Kurata Shunichi, Imai Takasuke
  • Organizer: 第35回日本集中治療医学会学術集会
  • Place of Presentation: 東京新宿京王プラザホテル
  • Year and Date: 2008-02-14
• [Presentation] The effect of TNF-a on microvascular permeability in an isolated perfused lung (2008)
  • Author(s): Georgieva Gabriela S, Kurata Shunichi, Bilali Aishan, Zhu Chengting, Imai Takasuke
  • Organizer: 第35回日本集中治療医学会学術集会
  • Place of Presentation: 東京新宿京王プラザホテル
  • Year and Date: 2008-02-14
• [Presentation] Injury of CPAP lung by mediators from isolated perfused unilateral hyperventilated rat lung (2008)
  • Author(s): Aishan Bilali, Chenting Zhu, Gabriela S Georgieva, Takasuke Imai
  • Organizer: 37^<th> Critical Care Congress
  • Place of Presentation: Hawaii Convention Center, Honolulu, Hawaii, USA
  • Year and Date: 2008-02-03
• [Presentation] Injury of CPA lung by mediators from isolated perfused unilateral hyperventilated rat lung (2008)
  • Author(s): Aishan Bilali, Chenting Zhu, Gabriela S Georgieva, TakasukeImai Takasuke
  • Organizer: Society of Critical Care Medicine's 37th Critical Care Congress
  • Place of Presentation: Hawaii Convention Center, Honolulu, Hawaii, USA
  • Year and Date: 2008-02-03
• [Presentation] Polymyxin B-immobilized fiber column hemoperfusion has the possibility to reduce endothelial activation in patients with septic shock (2008)
  • Author(s): Chieko Mitaka, Ymi Fujii, Yasuaki Nakajima, Kenrou Kawada, Takasuke Imai
  • Organizer: Society of Critical Care Medicine's 37th Critical Care Congress
  • Place of Presentation: Hawaii Convention Center, Honolulu, Hawaii, USA
  • Year and Date: 2008-02-03
• [Presentation] Effect of positive (5 mmHg) pulmonary venous pressure on isolated ischemic-reperfued rat lungs maintained at CPAP (2007)
  • Author(s): Georgieva GS, et. al.
  • Organizer: European Soc Inensive Care Med 20th Annual Meeting
  • Place of Presentation: Berlin, Germany
  • Year and Date: 2007-10-10
• [Presentation] Effect of positive(5 mmHg)pulmonary venous pressure on isolated ischemic-reperfused rat lungs maintained at CPAP (2007)
  • Author(s): Georgieva GS, Kurata S, Zhu C, Bilali A, Imai T
  • Organizer: 20^<th> Annual Congress of European Society of Intensive Care Medicine
  • Place of Presentation: Berlin, Germany
  • Year and Date: 2007-10-08
• [Presentation] Ameliorating effect of combination of apocynin and TACEI on ischemia/reperfusion(I/R)injury (2007)
  • Author(s): Chenting Zhu, Bilali Aishan, Gabriela Georgieva, Shunichi Kurata, Takasuke Imai
  • Organizer: 第34回日本集中治療医学会学術集会
  • Place of Presentation: 神戸国際展示場、神戸
  • Year and Date: 2007-03-02
• [Presentation] Induction of cytokine mRNA and edema in isolated perfused unilateral hyperventilated rat lung (2007)
  • Author(s): Bilali Aishan, Chenting Zhu, Gabriela Georgieva, Shunichi Kurata, Takasuke Imai
  • Organizer: 第34回日本集中治療医学会学術集会
  • Place of Presentation: 神戸国際展示場、神戸
  • Year and Date: 2007-03-02
• [Presentation] High tidal volume(TV)ventilation induced cytokine mRNA and edema in hyperventilated lung in isolated perfused unilateral hyperventilated lung (2007)
  • Author(s): Aishan Bilali, Chenting Zhu, Gabriela S Georgieva, Shunichi Kurata, Takasuke Imai
  • Organizer: 36^<th> Critical Care Congress
  • Place of Presentation: Gaylord Palms Resort and Cponvention Center Orlando, Florida, USA
  • Year and Date: 2007-02-18
• [Presentation] Ameliorating effect of combination of NADPH oxidase inhibitor(Apocynin)and TNF-α converting enzyme inhibitor(TACEI)on ishcmeia/reperfusion injury (2007)
  • Author(s): Chenting Zhu, Aishan Bilali, Gabriela S Georgieva, Shunichi Kurata, Takasuke Imai
  • Organizer: 36^<th> Critical Care Congress
  • Place of Presentation: Gaylord Palms Resort and Cponvention Center Orlando, Florida, USA
  • Year and Date: 2007-02-18
• [Presentation] Amelioration of ischemia-reperfusion(I/R)injury by NADPH oxidase inhibitor in isolated perfused rat lung (2006)
  • Author(s): Chenting Zhu, Asahn Bilali, Gabriela S Georgieva, Shunichi Kurata, Takasuke Imai
  • Organizer: 第34回日本救急医学会学術集会
  • Place of Presentation: 福岡国際会議場、福岡
  • Year and Date: 2006-10-30
• [Presentation] Development of a novel model for high tidal volume lung injury (2006)
  • Author(s): Aishan Bilali, Chenting Zhu, Georgieva Gabriela, Shunichi Kurata, Takasuke Imai
  • Organizer: 第34回日本救急医学会学術集会
  • Place of Presentation: 福岡国際会議場、福岡
  • Year and Date: 2006-10-30
• [Presentation] TNF-α converting enzyme inhibitor(TACEI)decreases control right lung injury induced by I/R left lung (2006)
  • Author(s): Gabriela S Georgieva, Takasuke Imai
  • Organizer: 第33回日本集中治療医学会学術集会
  • Place of Presentation: 大阪国際会議場、大阪
  • Year and Date: 2006-03-02
• [Presentation] Tumor necrosis factor-α converting enzyme inhibitor(TACEI)ameliorates control right lung(RL)injury by humoral mediators liberated from unilateral ischemia/reperfused(I/R)left lung(LL) (2006)
  • Author(s): Gabriela S Georgieva, Takasuke Imai, Shunichi Kurata
  • Organizer: 35^<th> Critical Care Congress
  • Place of Presentation: Moscone west convention center, SF, CA, USA
  • Year and Date: 2006-01-08
• [Presentation] Ischemic reperfused left lung(LL)increases expression of inflammatory cytokines mRNA in the control right lung(RL) (2005)
  • Author(s): Gabriela S Georgieva, Takasuke Imai, Shunichi Kurata
  • Organizer: 第33回日本救急医学会学術集会
  • Place of Presentation: 大宮ソニックシテイ、大宮
  • Year and Date: 2005-10-27
• [Book] 展望集中治療医学 (2008)
  • Author(s): 今井孝祐
  • Total Pages: 239
  • Publisher: 秀潤社