Division of Cardiology, Hospital for Sick Children, 555 University Ave, Toronto M5G 1X8, Canada.
Circulation. 2010 Mar 2;121(8):979-88. doi: 10.1161/CIRCULATIONAHA.109.850677. Epub 2010 Feb 16.
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.
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 approximately 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.
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.
在心室扩张或肥厚中，通常假设升高的舒张末期压力是继发于心肌僵硬度增加，但由于难度较大，很少在体内测量僵硬度。我们主要从先天性心脏病中测量了容积或压力超负荷心肌的体外被动僵硬度。
在心脏直视手术时获取心内膜心室活检（n=61；压力超负荷，36；容量超负荷，19；扩张型心肌病，4；正常供体，2）。在去皮组织中测量体外被动力-延伸曲线和刚性模量：肌条、提取肌丝的条带（主要是细胞外基质）和心肌细胞。测定胶原含量（n=38）和肌联蛋白同工型（n=16）。在心脏导管插入术时测量舒张末期压力（n=14）。压力超负荷组织（条带、细胞外基质、心肌细胞）的力和刚性模量比容量超负荷组织大 2.6 至 7.0 倍。在短拉伸（0.05 静息长度，L(0)）时，心肌细胞的力和刚性模量是压力超负荷>正常>容量超负荷>扩张型心肌病。在各种条件下，肌联蛋白 N2B:N2BA 同工型比例变化不大。在压力超负荷（35.1%）和容量超负荷（17.4%）条带中，细胞外基质对 0.05 L(0)时的力贡献大于正常心肌。刚性模量随压力超负荷但不随容量超负荷条带中的胶原含量增加而增加。在 0.05 L(0)时的体外刚性模量是压力超负荷而不是容量超负荷心室的体内舒张末期压力的良好预测因子，并估计正常舒张末期压力为 5 至 7mmHg。
在压力超负荷但不是容量超负荷的心室中，升高的舒张末期压力与心肌僵硬度增加有关。与容量超负荷心肌相比，压力超负荷心肌的僵硬度更高，这是由于细胞外基质和心肌细胞的僵硬度都更高。从正常到非常低僵硬度心肌细胞的转变可能标志着不可逆扩张。
