Passive Stiffness of Myocardium From Congenital Heart Disease and Implications for Diastole
Passive Stiffness of Myocardium From Congenital Heart Disease and Implications for Diastole
复制标题
DOI：
10.1161/circulationaha.109.850677
复制
发表时间：
2010-03-02
期刊：
影响因子：
37.8
通讯作者：
Kentish, Jonathan C.
中科院分区：
文献类型：
--
作者：
Chaturvedi, Rajiv R.;Herron, Todd;Kentish, Jonathan C.
背景：在心室扩张或肥厚中，舒张末期压力升高通常被认为是继发于心肌僵硬度增加，但由于困难，很少在体内测量僵硬度。我们测量了主要来自先天性心脏病的容量或压力过载心肌的体外被动僵硬度。方法与结果：心内直视手术患者行心内膜室活检（n = 61；压力过载36例；容量过载19例；扩张型心肌病4例；正常供者2例）。在皮肤组织：肌肉条、提取肌丝的肌肉条（主要是细胞外基质）和肌细胞中测量体外被动力延伸曲线和刚度模量。测定胶原含量（n = 38）和titin异构体（n = 16）。心导管插管时测量舒张末期压（n = 14）。压力超负荷组织（条状组织、细胞外基质、肌细胞）的力和刚度模量比体积超负荷组织高2.6- 7.0倍。在短时间拉伸（0.05静息长度，L-0）时，心肌细胞力和刚度模量为压力过载>正常，近似于容量过载>扩张型心肌病。Titin N2B: N2BA异构体比值在不同条件下变化不大。在0.05 L-0压力过载组（35.1%）和容量过载组（17.4%），细胞外基质对力的贡献大于正常心肌。弹性模量随胶原蛋白含量的增加而增加。0.05 L-0的体外刚度模量可以很好地预测压力过载而不是容量过载的心室的体内舒张末期压力，并且估计正常的舒张末期压力为5至7 mm hg。结论-压力过载而不是容量过载的心室舒张末期压力升高与心肌刚度增加有关。与容量负荷心肌相比，压力负荷心肌的刚度更大，这是由于细胞外基质和肌细胞的刚度更高。从正常到非常低硬度肌细胞的转变可能标志着不可逆的扩张。（Circulation. 2010; 121: 979-988）
Background-In ventricular dilatation or hypertrophy, an elevated end-diastolic pressure is often assumed to be secondary to increased myocardial stiffness, but stiffness is rarely measured in vivo because of difficulty. We measured in vitro passive stiffness of volume-or pressure-overloaded myocardium mainly from congenital heart disease.Methods and Results-Endocardial ventricular biopsies were obtained at open heart surgery (n = 61; pressure overload, 36; volume-overload, 19; dilated cardiomyopathy, 4; normal donors, 2). In vitro passive force-extension curves and the stiffness modulus were measured in skinned tissue: muscle strips, strips with myofilaments extracted (mainly extracellular matrix), and myocytes. Collagen content (n = 38) and titin isoforms (n = 16) were determined. End-diastolic pressure was measured at cardiac catheterization (n = 14). Pressure-overloaded tissue (strips, extracellular matrix, myocytes) had a 2.6- to 7.0-fold greater force and stiffness modulus than volume-overloaded tissue. Myocyte force and stiffness modulus at short stretches (0.05 resting length, L-0) was pressure-overloaded > normal approximate to volume-overloaded > dilated cardiomyopathy. Titin N2B: N2BA isoform ratio varied little between conditions. The extracellular matrix contributed more to force at 0.05 L-0 in pressure-overloaded (35.1%) and volume-overloaded (17.4%) strips than normal myocardium. Stiffness modulus increased with collagen content in pressure-overloaded but not volume-overloaded strips. In vitro stiffness modulus at 0.05 L-0 was a good predictor of in vivo end-diastolic pressure for pressure-overloaded but not volume-overloaded ventricles and estimated normal end-diastolic pressure as 5 to 7 mm Hg.Conclusions-An elevated end-diastolic pressure in pressure-overloaded, but not volume-overloaded, ventricles was related to increased myocardial stiffness. The greater stiffness of pressure-overloaded compared with volume-overloaded myocardium was due to the higher stiffness of both the extracellular matrix and myocytes. The transition from normal to very-low stiffness myocytes may mark irreversible dilatation. (Circulation. 2010; 121: 979-988.)