Molecular Biological Approach to Estimate the Effect of Left Ventricular Repair for Chronic Heart Failure

评估左心室修复对慢性心力衰竭效果的分子生物学方法

• 批准号: 12671306
• 负责人: NISHINA Takeshi
• 金额: $ 2.11万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671306/
• 关键词: Ischemic cardiomyopathy; Dilated cardiomyopathy; Left ventricular repair; Remodeling; myocardial infarction; Brain natriuretic peptide; endothelin-1; 心不全; 外科治療; 左室形成縮小術; Dor手術; Batista手術

Both ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) have a large left ventricular (LV) volume and a high wall tension. As a surgical treatment, LV repair (LVR) for ICM or DCM have been popular to reduce the LV volume. However, the effects of those procedures are not well understood, and we designed animal studies.LVR for ICM : ICM was developed in rats after anterior descending artery ligation. Rats were divided into LVR group or Sham group. LVR was performed by placating the infracted scar, and Sham operation was just thoracotomy. LV function was evaluated by echocardiography and cardiac catheterization. Brain natriuretic peptide (BNP) mRNA and endothelin-1 (ET-1) mRNA were measured by Nothern blot analysis. One week after surgery, LV motion and size improved in LVR group, and Emax was higher than in Sham group. However, all of them became similar 4 weeks after surgery. BNP mRNA was lower in LVR group at week 1, but not at week 4. ET-1 was higher in LVR group at week 1, but it was similar to that in Sham group at week 4.LVR for DCM : Dahl rats started an high-salt diet at the age of 7 weeks, and developed DCM about 40 weeks later. The DCM rats were randomized into LVR group or Sham group. LVR was performed by plicating the LV area between the papillary muscle bases. LV function was estimated by echocardiography and catheterization. Right after surgery, LV size decreased and LV motion improved in LVR group. LV re-dilation developed and Emax was the same level between the groups 4 weeks after surgery.Both in ICM and DCM models, LV size and function improved early after LVR, however, LV remodeling developed in late phase and deteriorated LV function. Prevention of postoperative LV remodeling is important to improve operative results.

缺血性心肌病（ICM）和扩张型心肌病（DCM）都有较大的左心室（LV）容积和较高的室壁张力。作为一种外科治疗，ICM或DCM的LV修复术（LVR）已流行以减少LV体积。然而，这些程序的效果还没有得到很好的理解，我们设计了动物实验。ICM的LVR：ICM是在大鼠前降支动脉结扎后形成的。将大鼠分为LVR组和Sham组。LVR采用瘢痕松解的方法，Sham手术采用开胸手术。通过超声心动图和心导管检查评价左室功能。采用免疫印迹法检测脑钠肽（BNP）和内皮素-1（ET-1）mRNA的表达。术后1周LVR组左室运动和大小改善，Emax高于Sham组。但术后4周，所有患者均恢复正常。LVR组BNP mRNA在第1周降低，但在第4周没有降低。DCM的LVR：Dahl大鼠7周龄开始高盐饮食，40周左右发生DCM。将DCM大鼠随机分为LVR组和Sham组。通过在乳头肌基底之间折叠LV区域进行LVR。通过超声心动图和导管插入术评估左室功能。术后即刻，LVR组的LV尺寸减小，LV运动改善。ICM和DCM模型在LVR后早期左室大小和功能均得到改善，但后期左室重构发生，左室功能恶化。预防术后左室重构对提高手术效果有重要意义。

项目成果

Takeshi Nishina, Kazunobu Nishimura, Sadatoshi Yuasa, Senri Miwa, Takuya Nomoto, Yutaka Sakakibara, Nobuhiro Handa, Ichiro Hamanaka, Yoshahiko Saito, Masashi Komeda: "Initial effects of the left ventricular repair by plication may not last long in a rat i

Takeshi Nishina、Kazunobu Nishimura、Sadatoshi Yuasa、Senri Miwa、Takuy​​a Nomoto、Yutaka Sakakibara、Nobuhiro Handa、Ichiro Hamanaka、Yoshahiko Saito、Masashi Komeda：“通过折叠术修复左心室的初始效果可能不会在大鼠体内持续很长时间。

Takeshi Nishina: "A Rat Model of Ischemic Cardiomyopathy for Investigating Left Ventricular Volume Reduction Surgery"Journal of Cardiac Surgery. (in press).

Takeshi Nishina：“用于研究左心室减容手术的缺血性心肌病大鼠模型”心脏外科杂志。

Takeshi Nishina, Kazunobu Nishimura, Sadatoshi Yuasa, Senri Miwa, Yutaka Sakakibara, Tadashi Ikeda, Masashi Komeda: "A Rat Model of Ischemic Cardiomyopathy for Investigating Left Ventricular Volume Reduction Surgery"J Card Surg. (in press).

Takeshi Nishina、Kazunobu Nishimura、Sadatoshi Yuasa、Senri Miwa、Yutaka Sakakibara、Tadashi Ikeda、Masashi Komeda：“用于研究左心室减容手术的缺血性心肌病大鼠模型”J Card Surg。

Takeshi Nishina: "Initial effects of the left ventricular repair by plication may not last long in a rat ischemic cardiomyopathy model"Circulation. 104(suppl I). I-241-I-245 (2001)

Takeshi Nishina：“在大鼠缺血性心肌病模型中，通过折叠术修复左心室的初始效果可能不会持续很长时间”循环。

Sadatoshi Yuasa: "A rat model of dilated cardiomyopathy to investigate partial left ventriculectomy"Journal of Cardiac Surgery. 16. 40-47 (2001)

Sadatoshi Yuasa：“用于研究部分左心室切除术的扩张型心肌病大鼠模型”心脏外科杂志。