扩张型缺血性心力衰竭中自体骨骼肌成肌细胞存活与左心室重构变化的相关性
Correlation of autologous skeletal myoblast survival with changes in left ventricular remodeling in dilated ischemic heart failure.
作者信息
McConnell Patrick I, del Rio Carlos L, Jacoby Douglas B, Pavlicova Martina, Kwiatkowski Pawel, Zawadzka Agatha, Dinsmore Jonathan H, Astra Louis, Wisel Sheik, Michler Robert E
机构信息
Department of Surgery, The Ohio State University, Columbus, Ohio, USA.
出版信息
J Thorac Cardiovasc Surg. 2005 Oct;130(4):1001. doi: 10.1016/j.jtcvs.2005.02.030. Epub 2005 Sep 2.
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/m2) 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%; dP/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 (R2 = 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.
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效果尚未得到严格研究。本研究的目的是确定自体骨骼肌成肌细胞在扩张型缺血性心力衰竭绵羊中的存活情况及其对左心室功能和重塑的影响。
方法
通过连续的左旋支冠状动脉微栓塞在绵羊（n = 11）中制造缺血性心力衰竭（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3.0×10⁸个成肌细胞；心力衰竭加自体骨骼肌成肌细胞组，n = 5）或未移植（心力衰竭对照组，n = 6）后，插入仪器用于长期测定左心室整体和局部尺寸、血流动力学以及压力-容积分析。在清醒动物中进行测量。
结果
在6周时，所有注射动物中均发现了源自自体骨骼肌成肌细胞的骨骼肌。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功能（左心室射血分数，29%±4%；dP/dT(max)，2863±152 mmHg/s；收缩末期弹性，1.6±0.22）或舒张功能（左心室舒张末期压力，21±2 mmHg；松弛时间常数（Tau），34±4 ms；dP/dT(min)，-1880±68 mmHg/s）。然而，自体骨骼肌成肌细胞移植后左心室扩张有所减轻（收缩末期容积指数变化，14%±4%对32%±6%；P <.05）。源自自体骨骼肌成肌细胞的骨骼肌的作用仅限于左心室短轴尺寸，且依赖于自体骨骼肌成肌细胞的存活（R² = 0.59，P =.006，n = 11）。
结论
自体骨骼肌心肌成形术能够减轻终末期缺血性心力衰竭绵羊的左心室重塑。
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