Correlation of autologous skeletal myoblast survival with changes in left ventricular remodeling in dilated ischemic heart failure
Correlation of autologous skeletal myoblast survival with changes in left ventricular remodeling in dilated ischemic heart failure
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DOI：
10.1016/j.jtcvs.2005.02.030
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发表时间：
2005-10-01
影响因子：
6
通讯作者：
Michler, RE
中科院分区：
文献类型：
--
作者：
McConnell, PI;del Rio, CL;Michler, RE
目的：自体骨骼肌成肌细胞移植在无冠状动脉血运重建的终末期缺血性心力衰竭中的作用尚未得到严格研究。本研究的目的是确定自体骨骼肌成肌细胞的存活及其对扩张性缺血性心力衰竭绵羊左室功能和重构的影响。（左心室射血分数，30% ± 2%;左心室收缩末期容积指数，82 +/- 9 mL/m2）。在自体骨骼肌成肌细胞移植（约3.0 × 10（8）成肌细胞;心力衰竭加自体骨骼肌成肌细胞组，n = 5）或不移植（心力衰竭对照组，n = 6）后，插入仪器以长期测定左心室整体和局部尺寸、血流动力学和压力-容积分析。测量.结果：6周时，所有动物体内均可见自体骨骼肌成肌细胞源性骨骼肌。在缺血性心力衰竭中，自体骨骼肌成肌细胞心肌成形术未能改善收缩压，（左心室射血分数，29% +/- 4%; dl/dT（max），2863 +/- 152 mm Hg/s;收缩末期弹性，1.6 +/- 0.22）或舒张期（左心室舒张末期压，21 +/- 2 mm Hg;舒张时间常数（Tau），34 +/- 4 ms; dP/dT（min），- 1880 +/- 68 mm Hg/s）功能。然而，自体骨骼成肌细胞移植后左心室扩张减弱（收缩末期容积指数变化，14% +/- 4% vs 32% +/- 6%; P <0.05）。自体骨骼肌成肌细胞衍生的骨骼肌的影响是排他性的左心室短轴尺寸和依赖于自体骨骼肌成肌细胞的生存（R-2 = 0.59，P = 0.006，n = 11）。结论：自体骨骼心肌成形术是能够减弱羊终末期缺血性心力衰竭的左心室重构。
Objectives: The effect of autologous skeletal myoblast transplantation has not been rigorously studied in the setting of end-stage ischemic heart failure free of concomitant coronary revascularization. The aims of the present study were to determine autologous skeletal myoblast survival and its effects on left ventricular function and remodeling in sheep with dilated ischemic heart failure.Methods: Ischemic heart failure (left ventricular ejection fraction, 30% +/- 2%; left ventricular end-systolic volume index, 82 +/- 9 mL/m(2)) was created in sheep (n = 11) with serial left circumflex coronary artery microembolizations. Instruments were inserted for the long-term determination of left ventricular global and regional dimensions, hemodynamics, and pressure-volume analysis after autologous skeletal myoblast transplantation (approximately 3.0 x 10(8) myoblasts; heart failure plus autologous skeletal myoblast group, n = 5) or without (heart failure-control group, n = 6). Measurements. were performed in conscious animals.Results: Autologous skeletal myoblast-derived skeletal muscle was found in all injected animals at 6 weeks. In ischemic heart failure, autologous skeletal myoblast cardiomyoplasty failed to improve systolic (left ventricular ejection fraction, 29% +/- 4%; dl/dT(max), 2863 +/- 152 mm Hg/s; end-systolic elastance, 1.6 +/- 0.22) or diastolic (left ventricular end-diastolic pressure, 21 +/- 2 mm Hg; time constant of relaxation (Tau), 34 +/- 4 ms; dP/dT(min), - 1880 +/- 68 mm Hg/s) function. There was, however, attenuation in the left ventricular dilatation after autologous skeletal myoblast transplantation (change in end-systolic volume index, 14% +/- 4% vs 32% +/- 6%; P < .05). The effects of autologous skeletal myoblast-derived skeletal muscle were exclusive to the left ventricular short-axis dimension and dependent on autologous skeletal myoblast survival (R-2 = 0.59, P = .006, n = 11).Conclusions: Autologous skeletal cardiomyoplasty was able to attenuate left ventricular remodeling in sheep with end-stage ischemic heart failure.