Myosin Cross-Bridge Dynamics in Patients With Hypertension and Concentric Left Ventricular Remodeling
Myosin Cross-Bridge Dynamics in Patients With Hypertension and Concentric Left Ventricular Remodeling
复制标题
DOI：
10.1161/circheartfailure.112.968925
复制
发表时间：
2012-11-01
影响因子：
9.7
通讯作者：
LeWinter, Martin M.
中科院分区：
文献类型：
--
作者：
Donaldson, Cameron;Palmer, Bradley M.;LeWinter, Martin M.
背景：高血压（HTN）引起同心性左心室重构，定义为相对壁厚增加或明显的左心室肥厚，并伴有舒张功能障碍。HTN和同心重构也是射血分数保持不变的心力衰竭的常见前兆。目前尚不清楚肌丝是否与同心重构患者的舒张功能障碍有关。方法与结果：对15例行冠状动脉搭桥术的男性患者进行术中心肌活检，左室射血分数和壁运动均正常。8例患者有HTN和同心重构史。没有HTN或重塑的7例作为对照。心肌条带解剖，去污剂脱膜。测量等长张力，在肌节长度2.2 μ m和pCa 8 ~ 4.5时进行正弦长度摄动分析。正弦分析提供了跨桥动力学的估计，包括连接和分离的速率常数和跨桥连接时间。HTN和对照组的归一化等距张力- pca关系相似。然而，HTN患者在亚最大[Ca2+] （pCa >= 6.5）时，桥间附着时间明显延长。蛋白磷酸化分析显示，HTN患者肌钙蛋白I的磷酸化水平降低了约25%
Background-Hypertension (HTN) causes concentric left ventricular remodeling, defined as an increased relative wall thickness or overt left ventricular hypertrophy, and associated diastolic dysfunction. HTN and concentric remodeling are also common precursors to heart failure with a preserved ejection fraction. It is not known whether the myofilament contributes to diastolic dysfunction in patients with concentric remodeling.Methods and Results-Intraoperative myocardial biopsies were obtained in 15 male patients undergoing coronary bypass grafting, all with normal left ventricular ejection fraction and wall motion. Eight patients had a history of HTN and concentric remodeling. Seven without HTN or remodeling served as controls. Myocardial strips were dissected and demembranated with detergent. Isometric tension was measured and sinusoidal length perturbation analysis performed at sarcomere length 2.2 mu m and pCa 8 to 4.5. Sinusoidal analysis provides estimates of cross-bridge dynamics, including rate constants of attachment and detachment and cross-bridge attachment time. The normalized isometric tension-pCa relation was similar in HTN and controls. However, cross-bridge attachment time was significantly prolonged at submaximal [Ca2+] (pCa >= 6.5) in HTN patients. Analysis of protein phosphorylation revealed approximate to 25% reduction in phosphorylation of troponin I in HTN patients (P