New therapeutical system establishment for end-stage heart failure by hybid application between mechanical, circulatory support and medical treatment

机械、循环支持和药物联合应用建立终末期心力衰竭新治疗体系

• 批准号: 13470269
• 负责人: SAKAMOTO Tohru
• 金额: $ 7.74万
• 依托单位: Tokyo Medical & Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470269/
• 关键词: left ventricular assist device; left ventricular mechanics; end-staged heart failure; left ventricular loop study; myocardial apotosis; mechanical circulatory support; 心節アポトーシス; 拍動型補助人工心臓; 左室等容収縮期; 連続流ポンプ; 心筋収縮能; 左室前負荷

Selective acute left heart failure(ALHF) had been induced by injecting the technopolymer(mic-rosphere : 20 micron in diameter) into the left main coronary artery in mongrael dogs. The dogs were devided into four groups as follows ; (1)control study group to observe ALHF course (G-1), (2)dogs with circulatory support by ventricular assist device (VAD) via left atrial cannula (G-2), (3)dogs with VAD via left ventricular cannula, supported with fixed pulsatile driven with native heart (G-3), and (4) dogs like as G-3, but simultaneous driven with native heart (G-4). We studied left ventricular (LV) mechanics analyzing LV loop, which had been investigated from the first year of this research program, and have been analyzed the myocardial deformation by microscopic/electron microscopic methods and mRNA changes in beta-adrenergic receptors, angiotensin II type-1 receptors as well as parameters (Bcl-xl/Bax) evaluating cellular apotosisIntramyocardial edem and myocardial derangements were micro … More scopically observeed in G-land G-2, but G-3 showed alomost normal findings like as pre-support. In electron microscopic studies, various sized mitochondria were observed in G-1/2, but normal sizes in G-3 with no myofibril derangements. These cellular findings were calculated using imaze analysis system by computer, resulted in comfirming the evidences with statistics. Immnunobinding assy studies showed elevated signals in beta-1-adrenalin receptor in G-3 which myocardial inotropic power might be attenuated to recovery, and mRNA of angiotensin 2 type-1 receptor was also elevated in G-2 revealing the elevated afterload inspite of VAD. Bcl-xl/Bax did not change in any stitua-tions, resulted in being unable to judge cellular apotosis during 4 hours VAD supportComclusions : (1)VAD with apical cannula keeps normal cellular anatomy, (2)signals in beta-1-adrenalin receptor are increased in VAD with apical cannula, suggesting the reserved inotropic power within VAD support, (3)signals of angiotensin 2 type-1 receptor are increased in VAD with atrial cannula, sugesting the elevated afterload, anr (4)myocardial apotosis was not prevented enough during four circulatory support with VAD Less

将聚合物微球（直径20 μ m）注射于犬左冠状动脉主干内，诱发选择性急性左心衰（ALHF）。将狗分为以下四组：（1）对照研究组，观察ALHF过程（G-1），（2）通过左心房插管使用心室辅助装置（VAD）进行循环支持的犬（G-2），（3）通过左心室插管使用VAD，使用自体心脏驱动的固定搏动进行支持的犬（G-3），以及（4）与G-3相似的犬，但同时与自体心脏驱动（G-4）。本研究从第一年开始对左室环进行力学分析，并对左室环的心肌变形进行了光镜和电镜分析，同时对β-肾上腺素能受体、血管紧张素Ⅱ 1型受体mRNA的变化以及细胞凋亡指标（Bcl-xl/Bax）进行了分析。 ...更多信息 在G-和G-2中进行了显微镜检查，但G-3显示了几乎正常的结果，如前支持。在电镜研究中，在G-1/2中观察到不同大小的线粒体，但在G-3中观察到正常大小的线粒体，没有肌原纤维紊乱。用imaze计算机分析系统计算细胞学结果，结果与统计学结果相符。免疫组化结果显示，G-3大鼠β 1肾上腺素受体信号增强，心肌变力减弱，恢复后，G-2大鼠血管紧张素21型受体mRNA表达增强，提示尽管有VAD，但后负荷仍增加。Bcl-xl/Bax在VAD支持4 h内无任何变化，导致不能判断细胞凋亡。（1）心尖部插管的VAD维持了正常的细胞解剖结构;（2）心尖部插管的VAD中β 1肾上腺素受体信号增加，提示VAD支持中保留的变力作用，（3）心房插管VAD时血管紧张素21型受体信号增强，提示后负荷增加;（4）VAD四次循环支持时心肌细胞凋亡未能得到有效预防。

项目成果

坂本 徹: "慢性心不全のFrontier:心不全の外科治療の最前線"Heart View. 7. 123-128 (2002)

Toru Sakamoto：“慢性心力衰竭的前沿：心力衰竭外科治疗的前沿”Heart View。7. 123-128 (2002)。

Takatani S, Sakamoto T, Nakamura M, Arai H, Ouchi K, Mizuno T.: "One-piece Ultracompact totally implantable electromechanical total artificial heart for permanent use"ASAIO Journal. 48(5). 538-545 (2002)

Takatani S、Sakamoto T、Nakamura M、Arai H、Ouchi K、Mizuno T.：“永久使用的一件式超紧凑型完全植入式机电全人工心脏”ASAIO 杂志。

Takatani Setsuo: "One-piece Ultracompact totally implantable electromechanical total artificial heart for permanent use"American Soc.Artifi. Intern, Organs Journal. 48(5). 538-545 (2002)

Takatani Setsuo：“永久使用的一件式超紧凑型完全植入式机电全人工心脏”美国 Soc.Artifi。

Sakamoto T (Takano T, Seinio H editated): "Congestive Heart Failure Mannual : Diagnosis & Treratment, IV・Mechanical treatments"Medical Journal Publishing Com.. 267-270 (2002)

坂本T（高野T、Seinio H编辑）：“充血性心力衰竭手册：诊断和治疗、IV·机械治疗”医学杂志出版公司.. 267-270（2002）

Setsuo Takatani: "One-piece ultracompact totally implantable electro-mechanical total artificial heart for permanent use"ASAIO Journal. Vol.48. 538-545 (2002)

Setsuo Takatani：“永久使用的一件式超紧凑型完全植入式机电全人工心脏”ASAIO 杂志。