Cardiomyocyte stiffness in Diastolic heart failure
Cardiomyocyte stiffness in Diastolic heart failure
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DOI：
10.1161/01.cir.0000155257.33485.6d
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发表时间：
2005-02-15
期刊：
影响因子：
37.8
通讯作者：
Paulus, WJ
中科院分区：
文献类型：
--
作者：
Borbély, A;van der Velden, J;Paulus, WJ
背景-保留左心室射血分数（EF）的心力衰竭越来越被认识，通常被称为舒张性心力衰竭（DHF）。其发病机制尚不清楚，部分原因是缺乏心肌活检材料。因此，对DHF患者的心内膜活检样本进行胶原体积分数（CVF）和肉瘤蛋白组成分析，并与对照样本进行比较。从这些活检样本中分离单个心肌细胞以评估细胞收缩性能。方法与结果- DHF患者（n = 12） LVEF为71 +/- 11%，左室舒张末期压（LVEDP）为28 +/- 4 mm Hg，无明显冠状动脉狭窄。DHF患者的CVFs （7.5 +/- 4.0%, P < 0.05）高于对照组（n = 8, 3.8 +/- 2.0%），且肌体蛋白组成未见明显变化。将机械分离的心肌细胞用Triton X-100去除所有膜，拉伸至肌节长度为2.2 μ m，并用含有不同[Ca2+]的溶液活化。与对照组心肌细胞相比，DHF患者的心肌细胞在最大[Ca2+]时产生相似的总等长力，但在没有Ca2+时，其静息张力（f被动）几乎是其两倍高（6.6 +/- 3.0 vs 3.5 +/- 1.7 kN/m） (2), P < 0.001)。f -被动和CVF联合使用与LVEDP的相关性比单独使用更强。给DHF心肌细胞注射蛋白激酶A （PKA）可降低f -被动值至控制值。结论- DHF患者心肌细胞更硬，这可以从相同肌节长度的较高f -被动反应中看出。与CVF一起，f -被动决定了体内舒张期左室功能障碍。PKA对这种高f被动反应的纠正表明，DHF参与了肌合成蛋白磷酸化的降低。
Background - Heart failure with preserved left ventricular (LV) ejection fraction (EF) is increasingly recognized and usually referred to as diastolic heart failure (DHF). Its pathogenetic mechanism remains unclear, partly because of a lack of myocardial biopsy material. Endomyocardial biopsy samples obtained from DHF patients were therefore analyzed for collagen volume fraction (CVF) and sarcomeric protein composition and compared with control samples. Single cardiomyocytes were isolated from these biopsy samples to assess cellular contractile performance.Methods and Results - DHF patients ( n = 12) had an LVEF of 71 +/- 11%, an LV end-diastolic pressure (LVEDP) of 28 +/- 4 mm Hg, and no significant coronary artery stenoses. DHF patients had higher CVFs ( 7.5 +/- 4.0%, P < 0.05) than did controls ( n = 8, 3.8 +/- 2.0%), and no conspicuous changes in sarcomeric protein composition were detected. Cardiomyocytes, mechanically isolated and treated with Triton X-100 to remove all membranes, were stretched to a sarcomere length of 2.2 mu m and activated with solutions containing varying [Ca2+]. Compared with cardiomyocytes of controls, cardiomyocytes of DHF patients developed a similar total isometric force at maximal [Ca2+], but their resting tension (F-passive) in the absence of Ca2+ was almost twice as high (6.6 +/- 3.0 versus 3.5 +/- 1.7 kN/m(2), P < 0.001). F-passive and CVF combined yielded stronger correlations with LVEDP than did either alone. Administration of protein kinase A (PKA) to DHF cardiomyocytes lowered F-passive to control values.Conclusions - DHF patients had stiffer cardiomyocytes, as evident from a higher F-passive at the same sarcomere length. Together with CVF, F-passive determined in vivo diastolic LV dysfunction. Correction of this high F-passive by PKA suggests that reduced phosphorylation of sarcomeric proteins is involved in DHF.