University of California San Diego, Department of Bioengineering, La Jolla, CA 92093-0412, USA.
J Biomech. 2012 Mar 15;45(5):865-71. doi: 10.1016/j.jbiomech.2011.11.028. Epub 2011 Dec 12.
The postnatal heart grows mostly in response to increased hemodynamic load. However, the specific biomechanical stimuli that stimulate cardiac growth as a reaction to increased hemodynamic load are still poorly understood. It has been shown that isolated neonatal rat cardiac myocytes normalize resting sarcomere length by adding sarcomeres in series when subjected to uniaxial static strain. Because there is experimental evidence that myocytes can distinguish the direction of stretch, it was postulated that myocytes also may normalize interfilament lattice spacing as a response to cross-fiber stretch.
A growth law was proposed in which fiber axial growth was stimulated by fiber strain deviating from zero and fiber radial growth by cross-fiber strain (parallel to the wall surface) deviating from zero. Fiber radial growth rate constant was 1/3 of the fiber axial growth rate constant. The growth law was implemented in a finite element model of the newborn Sprague-Dawley rat residually stressed left ventricle (LV). The LV was subjected to an end-diastolic pressure of 1 kPa and about 25 weeks of normal growth was simulated.
Most cellular and chamber dimension changes in the model matched experimentally measured ones: LV cavity and wall volume increased from 2.3 and 54 μl, respectively, in the newborn to 276 μl and 1.1 ml, respectively, in the adult rat; LV shape became more spherical; internal LV radius increased faster than wall thickness; and unloaded sarcomere lengths exhibited a transmural gradient. The major discrepancy with experiments included a reversed transmural gradient of cell length in the older rat.
A novel strain-based growth law has been presented that reproduced physiological postnatal growth in the rat LV.
出生后的心脏主要通过增加血流动力学负荷来生长。然而,刺激心脏生长以应对增加的血流动力学负荷的具体生物力学刺激仍知之甚少。已经表明,在受到单轴静态应变时,分离的新生大鼠心肌细胞通过串联添加肌节来使静息肌节长度正常化。由于有实验证据表明心肌细胞可以区分拉伸的方向,因此推测心肌细胞也可以作为对交叉纤维拉伸的反应来使肌丝间晶格间距正常化。
提出了一种生长定律,其中纤维轴向生长受纤维应变偏离零的刺激,纤维径向生长受交叉纤维应变(平行于壁面)偏离零的刺激。纤维径向生长速率常数是纤维轴向生长速率常数的 1/3。该生长定律在新生 Sprague-Dawley 大鼠残余应力左心室(LV)的有限元模型中得到了实现。LV 受到 1 kPa 的舒张末期压力,模拟了大约 25 周的正常生长。
模型中的大多数细胞和腔室尺寸变化与实验测量值相匹配:LV 腔和壁体积分别从新生儿的 2.3 和 54 μl 增加到成年大鼠的 276 μl 和 1.1 ml;LV 形状变得更圆;内部 LV 半径的增加速度快于壁厚度;卸载的肌节长度表现出壁内梯度。与实验的主要差异包括老年大鼠细胞长度的逆壁内梯度。
提出了一种新的基于应变的生长定律,该定律再现了大鼠 LV 的生理出生后生长。