Department of Biomedical Engineering, School of Engineering, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Am J Physiol Heart Circ Physiol. 2010 Nov;299(5):H1577-87. doi: 10.1152/ajpheart.00406.2010. Epub 2010 Aug 20.
The twisting and untwisting motions of the left ventricle (LV) lead to efficient ejection of blood during systole and filling of the ventricle during diastole. Global LV mechanical performance is dependent on the contractile properties of cardiac myocytes; however, it is not known how changes in contractile protein expression affect the pattern and timing of LV rotation. At the myofilament level, contractile performance is largely dependent on the isoforms of myosin heavy chain (MHC) that are expressed. Therefore, in this study, we used MRI to examine the in vivo mechanical consequences of altered MHC isoform expression by comparing the contractile properties of hypothyroid rats, which expressed only the slow β-MHC isoform, and euthyroid rats, which predominantly expressed the fast α-MHC isoform. Unloaded shortening velocity (V(o)) and apparent rate constants of force development (k(tr)) were measured in the skinned ventricular myocardium isolated from euthyroid and hypothyroid hearts. Increased expression of β-MHC reduced LV torsion and fiber strain and delayed the development of peak torsion and strain during systole. Depressed in vivo mechanical performance in hypothyroid rats was related to slowed cross-bridge performance, as indicated by significantly slower V(o) and k(tr), compared with euthyroid rats. Dobutamine infusion in hypothyroid hearts produced smaller increases in torsion and strain and aberrant transmural torsion patterns, suggesting that the myocardial response to β-adrenergic stress is compromised. Thus, increased expression of β-MHC alters the pattern and decreases the magnitude of LV rotation, contributing to reduced mechanical performance during systole, especially in conditions of increased workload.
左心室（LV）的扭曲和松解运动导致收缩期血液有效射出，舒张期心室充盈。LV 的整体机械性能取决于心肌细胞的收缩特性；然而，目前尚不清楚收缩蛋白表达的变化如何影响 LV 旋转的模式和时间。在肌丝水平上，收缩性能在很大程度上取决于表达的肌球蛋白重链（MHC）同工型。因此，在这项研究中，我们通过比较仅表达慢 β-MHC 同工型的甲状腺功能减退大鼠和主要表达快 α-MHC 同工型的甲状腺功能正常大鼠，使用 MRI 检查了 MHC 同工型表达改变的体内机械后果。在从甲状腺功能正常和甲状腺功能减退的心脏中分离出的去皮心室心肌中测量未加载缩短速度（V(o)）和力发展的表观速率常数（k(tr)）。β-MHC 的表达增加减少了 LV 扭转和纤维应变，并延迟了收缩期峰值扭转和应变的发展。与甲状腺功能正常的大鼠相比，甲状腺功能减退大鼠体内机械性能降低与肌球蛋白横桥性能减慢有关，这表现为 V(o)和 k(tr)明显减慢。在甲状腺功能减退的心脏中给予多巴酚丁胺输注会导致扭转和应变的增加较小，并且出现异常的跨壁扭转模式，表明心肌对β-肾上腺素能应激的反应受损。因此，β-MHC 的表达增加改变了 LV 旋转的模式并降低了其幅度，导致收缩期机械性能降低，尤其是在工作量增加的情况下。
