DYNAMIC CARDIOMYOPLASTY

动态心肌成形术

基本信息

  • 批准号:
    6184306
  • 负责人:
  • 金额:
    $ 42.48万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1999
  • 资助国家:
    美国
  • 起止时间:
    1999-04-01 至 2002-03-31
  • 项目状态:
    已结题

项目摘要

Cardiomyoplasty (CMP), a surgical treatment for heart failure, has several advantages: skeletal muscle requires no external power source; each patient serves as his/her "donor;" and rejection is not a problem. CMP prevents systolic bulging and inhibits progressive ventricular enlargement. Both mechanisms probably contribute to subjective decrease in symptoms and may explain phase II clinical CMP trials, in which, progressive left ventricular (LV) enlargement was inhibited. However, experimentally and clinically, systolic augmentation of LV function by latissimus dorsi muscle (LDM) is rarely observed. This is a major problem. Our view is that CMP will not thrive as a viable approach without physiologically important large increases in LV pressure and outflow with LDM stimulation. Our goal is to achieve these large pressure and flow increases. Our approach is to systematically examine this problem by sequentially measuring the effects of different interventions. Typically, CMP studies try some intervention, and only examine the effects after LDM training. We believe that this has been a major mistake, and has actually slowed progress. Important improvements may have been missed. Our approach is to maximize the response at 2 weeks after surgery (already accomplished). Then from this foundation, obtain the best results at 1, 2, and 3 months. This grant will examine preconditioning (for revascularization) and daily rest periods (intermittent stimulation). Our aims are for little, if any, LDM damage and a strong, yet fatigue resistant, muscle. With this muscle, LDM stimulation should increase LV pressure by 15 to 20 mmHg and stroke volume by 20 to 30 percent. We will test these interventions in 2 sections. In both, LV function will be depressed by intra-coronary microsphere injections. In preconditioning studies, vascular delay (dividing part of vascular supply prior to surgery) and/or injections of bFGF will be tested to stimulate revascularization and decrease LDM damage. Dogs will be randomly divided into control, standard CMP, CMP with vascular delay, and CMP with vascular delay plus bFGF groups. Revascularization will be assessed histologically and by measuring regional LDM blood flow and vascular growth factors. At 2 weeks, 1, 2, and 3 months, LV function will be assessed. In intermittent stimulation studies, after preconditioning, dogs will be randomly divided into continuous (24 hours/day) vs intermittent LDM stimulation groups (stimulator off 8 hrs/day). At 2 weeks, 1, 2, and 3 months, LV function will be assessed. The mechanisms will be examined by immuno-histochemical techniques and by experiments to assess LDM mechanical performance. In preliminary experiments, the results have reached our goals: 19 mmHg increases in peak LV pressure and 40 percent increases in stroke volume. These very large increases are consistent with our hypothesis and show that significant increases in LV pressure and stroke volume can occur with LDM stimulation.
心肌成形术(CMP)是一种治疗心力衰竭的外科手术,有几个优点:骨骼肌不需要外部电源;每个病人都是他/她的"供体";排斥反应不是问题。 CMP防止收缩期膨胀并抑制进行性心室扩大。 这两种机制可能有助于主观症状的减轻,并可能解释II期临床CMP试验,其中,进行性左心室(LV)扩大受到抑制。 然而,在实验和临床上,很少观察到背阔肌(LDM)对LV功能的收缩期增强。这是一个大问题。 我们的观点是,如果没有生理上重要的LV压力和LDM刺激流出量的大幅增加,CMP将不会作为一种可行的方法而蓬勃发展。 我们的目标是实现这些大的压力和流量增加。 我们的方法是系统地研究这个问题,通过连续测量不同干预措施的效果。通常情况下,CMP研究尝试一些干预,并只检查LDM训练后的效果。 我们认为,这是一个重大错误,实际上减缓了进展。 重要的改进可能被忽略了。 我们的方法是在手术后2周(已经完成)最大化反应。然后在此基础上,在1,2和3个月时获得最佳效果。 该补助金将检查预处理(用于血运重建)和每日休息期(间歇性刺激)。 我们的目标是很少,如果有的话,LDM的损害和强大的,但抗疲劳,肌肉。 有了这块肌肉,LDM刺激应该会使LV压力增加15到20 mmHg,每搏输出量增加20到30%。 我们将在两个部分测试这些干预措施。 在这两种情况下,冠状动脉内微球注射都会抑制LV功能。 在预处理研究中,将测试血管延迟(手术前分割部分血管供应)和/或bFGF注射以刺激血运重建和减少LDM损伤。将犬随机分为对照组、标准CMP组、CMP+血管延迟组和CMP+血管延迟+bFGF组。 将通过组织学和测量局部LDM血流和血管生长因子来评估血运重建。在2周、1、2和3个月时,将评估LV功能。 在间歇性刺激研究中,预处理后,将犬随机分为连续(24小时/天)与间歇性LDM刺激组(刺激器关闭8小时/天)。在2周、1个月、2个月和3个月时,将评估LV功能。将通过免疫组织化学技术和实验来检查机制,以评估LDM机械性能。 在初步实验中,结果达到了我们的目标:左心室峰值压力增加19 mmHg,每搏输出量增加40%。 这些非常大的增加与我们的假设一致,表明LDM刺激可导致LV压力和每搏输出量显著增加。

项目成果

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WILLIAM P SANTAMORE其他文献

WILLIAM P SANTAMORE的其他文献

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{{ truncateString('WILLIAM P SANTAMORE', 18)}}的其他基金

DYNAMIC CARDIOMYOPLASTY
动态心肌成形术
  • 批准号:
    2842829
  • 财政年份:
    1999
  • 资助金额:
    $ 42.48万
  • 项目类别:
DYNAMIC CARDIOMYOPLASTY
动态心肌成形术
  • 批准号:
    6389888
  • 财政年份:
    1999
  • 资助金额:
    $ 42.48万
  • 项目类别:
THERMODILUTION RIGHT VENTRICULAR EJECTION FRACTION
热稀释右心室射血分数
  • 批准号:
    2863525
  • 财政年份:
    1999
  • 资助金额:
    $ 42.48万
  • 项目类别:
MICROWAVE SYSTEM FOR TISSUE ANASTOMOSES
用于组织吻合的微波系统
  • 批准号:
    2234393
  • 财政年份:
    1995
  • 资助金额:
    $ 42.48万
  • 项目类别:
SMALL INSTRUMENTATION GRANT
小型仪器补助金
  • 批准号:
    3525713
  • 财政年份:
    1991
  • 资助金额:
    $ 42.48万
  • 项目类别:
RIGHT VENTRICULAR FUNCTION
右心室功能
  • 批准号:
    3357446
  • 财政年份:
    1989
  • 资助金额:
    $ 42.48万
  • 项目类别:
RIGHT VENTRICULAR FUNCTION
右心室功能
  • 批准号:
    3357444
  • 财政年份:
    1989
  • 资助金额:
    $ 42.48万
  • 项目类别:
RIGHT VENTRICULAR FUNCTION
右心室功能
  • 批准号:
    3357445
  • 财政年份:
    1989
  • 资助金额:
    $ 42.48万
  • 项目类别:
VENTRICULAR INTERDEPENDENCE
心室相互依赖性
  • 批准号:
    3350655
  • 财政年份:
    1989
  • 资助金额:
    $ 42.48万
  • 项目类别:
CORONARY STENOSIS, VASOMOTION AND THROMBUS FORMATION
冠状动脉狭窄、血管舒缩和血栓形成
  • 批准号:
    3350611
  • 财政年份:
    1989
  • 资助金额:
    $ 42.48万
  • 项目类别:

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