Molecular mechanism of myocardial pharmacological preconditioning via activation of PI3K-Akt.

• Project/Area Number: 18791086
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: Nagasaki University
• Principal Investigator: YOSHITOMI Osamu Nagasaki University, 大学病院, 助教 (30380926)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,710,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥210,000); Fiscal Year 2008: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2007: ¥900,000 (Direct Cost: ¥900,000); Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
• Keywords: 心筋虚血再灌流障害 / 心筋スタニング / 薬理学的プレコンディショニング / phosphodiesterase-III阻害薬 / Rho-kinase阻害薬、p38MAPK / Rho-kinase阻害薬 / ホスホジエステラーゼIII阻害薬 / ミトコンドリアATP感受性Kチャネル / プレコンディショニング / 発作性心房細動 / 塩酸ランジオロール / p38MAPK / 再灌流性不整脈 / cAMP

Research Abstract

豚の生体モデルを用いて臨床使用が可能な循環作動薬の薬理学的プレコンディショニング効果及び機序について検討した。心筋虚血再灌流モデルを作製し、phosphodiesterase (PDE)-III阻害薬、cAMP増強薬、Rho-kinase阻害薬の虚血前投与が心筋スタニングからの回復を改善し、再灌流性不整脈も抑制したことを明らかにした。またPDE-III阻害薬の保護作用にはp38 mitogen-activated protein kinase(p38MAPK)の活性化が関与することを明らかにした。

Research Products

• [Journal Article] The impact of administration time of milrinone, a phosphodiesterase III inhibitor, to protect swine myocardium against ischemia-reperfusion injury. (2009)
  • Author(s): Shibata I, Yoshitomi O, Maekawa T, Hara T, Cho S, Sumikawa K
  • Journal Title: Masui 58
  • Peer Reviewed
• [Journal Article] Effect of low-dose landiolol hydrochloride on atrial fibrillation after cardiovascular surgery in patients with low left ventricular function. (2009)
  • Author(s): Yoshitomi O, Maekawa T, Makita T, Sumikawa K
  • Journal Title: Masui 58
  • Peer Reviewed
• [Journal Article] Administration of the Rho-kinase inhibitor fasudil before ischemia or just after reperfusion, but not 30 min after reperfusion, protects the stunned myocardium in swine. (2008)
  • Author(s): Shibata I, Yoshitomi O, Use T, Ureshino H, Cho S, Maekawa T, Hara T, Sumikawa K
  • Journal Title: Cardiovascular Drugs and Therapy 22 Pages: 293-8
  • NAID: 120006983692
  • Peer Reviewed
• [Journal Article] Olprinone induced myocardial preconditioning is not attenuated by mitochondrial K-ATP channels antagonist. (2008)
  • Author(s): Matsumoto S, Cho S, Maekawa T, Yoshitomi O, Shibata I, Sumikawa K
  • Journal Title: J Anesth 22
  • Peer Reviewed
• [Journal Article] Administration of the Rho-Kinase Inhibitor Fasudil Before Is chemia or just After Reperfusion, but not 30 min After Rep erfusion. Protects the Stunned Mvocardium in Swine (2008)
  • Author(s): Itsuko Shibata
  • Journal Title: Cardiovascular Drugs and Therapy 22 Pages: 293-298
  • Peer Reviewed
• [Journal Article] Olprinone induced myocardial preconditioning is not attenuated by mitochondrial K-ATP channels antagonist (2008)
  • Author(s): Shuhei Matsumoto
  • Journal Title: J Anesth 22
  • Peer Reviewed
• [Journal Article] Role of p38 MAPK in the cardioprotective effect of milrinone against myocardial stunning in swine. (2007)
  • Author(s): Yoshitomi O, Hara T, Shibata I, Cho S, Sumikawa K
  • Journal Title: Anesthesiology 107
  • NAID: 40021157468
  • Peer Reviewed
• [Journal Article] Role of p38MAPK in the cardioprotective effect of milrinone against myocardial stunning in swine. (2007)
  • Author(s): Osamu Yoshitomi
  • Journal Title: Anesthesiology 107 Pages: 626-626
  • NAID: 40021157468
  • Peer Reviewed
• [Journal Article] Fasudil administered immediately after reperfusion protects against myocardial stunning in swine (2007)
  • Author(s): Itsuko Shibata
  • Journal Title: Anesthesiology 107 Pages: 624-624
  • Peer Reviewed
• [Journal Article] Milrinone administered before ischemia or just after reperfusion, attenuates myocardial stunning in anesthetized swine. (2006)
  • Author(s): Use T, Makita T, Ureshino H, Cho S, Yoshitomi O, Akiyama D, Oshibuchi M, Hara T, Sumikawa K
  • Journal Title: Cardiovascular Drugs and Therapy 20 Pages: 327-34
  • Peer Reviewed
• [Journal Article] Cardioprotective effects of colforsin daropate hydrochloride on stunned myocardium in pigs. (2006)
  • Author(s): Yoshitomi O, Hara T, Shibata I, Akiyama D, Sumikawa K
  • Journal Title: Anesthesiology 105
  • Peer Reviewed
• [Journal Article] Milrinone administered before ischemia or just after reperfusion, attenuates myocardial stunning in anesthetized swine. (2006)
  • Author(s): Use T, Yoshitomi O, 他 7 名
  • Journal Title: Cardiovasc Drugs Ther 20 Pages: 327-334
• [Journal Article] Cardioprotective effects of colforsin daropate hydrochloride on stunned myocardium in anesthetized pigs. (2006)
  • Author(s): Yoshitomi O, 他 4 名
  • Journal Title: Anesthesiology 105
• [Journal Article] Fasudil-administered before or after ischemia protects stunned myocardial stunning in swine. (2006)
  • Author(s): Shibata I, Yoshitomi O, 他 3 名
  • Journal Title: Anesthesiology 105
• [Presentation] 低心機能患者の心・大血管手術後心房細動に対する低用量塩酸ランジオロールの効果 (2008)
  • Author(s): 吉富修
  • Organizer: 日本麻酔科学会
  • Place of Presentation: 神戸
  • Year and Date: 2008-08-17
• [Presentation] Role of p38 MAPK in the cardioprotective effect of milrinone against myocardial stunning in swine. (2007)
  • Author(s): Yoshitomi O
  • Organizer: ASA
  • Place of Presentation: San Francisco
  • Year and Date: 2007-10-05
• [Presentation] 心筋スタニングに対するミルリノンの保護作用におけるp38MAPKの役割 (2007)
  • Author(s): 吉富修
  • Organizer: 日本麻酔科学会
  • Place of Presentation: 札幌
  • Year and Date: 2007-06-01
• [Presentation] 心筋スタニングに対するミルリノンの保護作用におけるp38MAPKの役割 (2007)
  • Author(s): 吉富 修
  • Organizer: 日本麻酔科学会第54回学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2007-06-01
• [Presentation] Cardioprotective effects of colforsin daropate hydrochloride on stunned myocardium in pigs. (2006)
  • Author(s): Yoshitomi O
  • Organizer: ASA
  • Place of Presentation: Chicago
  • Year and Date: 2006-10-14
• [Presentation] 塩酸コルホルシンダロパートの虚血前投与が心筋スタニングからの回復に与える影響 (2006)
  • Author(s): 吉富修
  • Organizer: 日本麻酔科学会
  • Place of Presentation: 神戸
  • Year and Date: 2006-06-02