心力衰竭患者化学处理后的心室小梁中肌浆网和肌丝的功能

Sarcoplasmic reticulum and myofilament function in chemically-treated ventricular trabeculae from patients with heart failure.

作者信息

Denvir M A, MacFarlane N G, Cobbe S M, Miller D J

机构信息

Department of Medical Cardiology, Glasgow Royal Infirmary, UK.

出版信息

Cardiovasc Res. 1995 Sep;30(3):377-85.

PMID:7585829

Abstract

OBJECTIVES

Assessment of sarcoplasmic reticulum calcium-loading ability, myofilament force production and myofilament calcium sensitivity in ventricular trabeculae from patients with heart failure.

METHODS

Right ventricular trabeculae (diameter 150-250 microns) were obtained from 18 patients undergoing elective cardiac transplantation. These were mounted for isometric tension measurement and treated with saponin which permeabilises the sarcolemma leaving the sarcoplasmic reticulum (SR) functionally intact. The trabecula was bathed in a mock intracellular solution containing ATP and weakly buffered [Ca2+] at various concentrations (150-400 nM). The amplitude of caffeine-induced contractures was used as a quantitative measure of the SR calcium content and was correlated with the clinical severity of heart failure. The same trabecula was then exposed to a solution containing Triton-X100 (1%) which destroys all cell membranes leaving only the myofilaments intact. The maximum calcium-activated force (Cmax) and myofilament responsiveness to calcium was assessed.

RESULTS

Patients with ischaemic heart disease (IHD) and severe heart failure (PCWP > 20 mm Hg, ejection fraction < 15%, n = 8) demonstrated low SR Ca(2+)-loading ability compared with patients with IHD and moderate heart failure (PCWP-20 mmHg, LV ejection fraction > 20%, n = 6). Patients with dilated cardiomyopathy (DCM) (n = 4) demonstrated SR Ca(2+)-loading ability which was lower than either of the two IHD groups. Myofilament force production (per unit cross-sectional area) was not significantly different between the three groups. Myofilament responsiveness to Ca2+ demonstrated no relationship with severity of heart failure.

CONCLUSIONS

In human heart failure, SR Ca(2+)-loading ability diminishes with increasing severity of heart failure. Myofilament force production and sensitivity to calcium are unaffected by severity of heart failure.

摘要

目的

评估心力衰竭患者心室小梁肌浆网钙装载能力、肌丝力产生及肌丝钙敏感性。

方法

从18例接受择期心脏移植的患者获取右心室小梁（直径150 - 250微米）。将其安装用于等长张力测量，并用皂素处理，皂素可使肌膜通透，而肌浆网（SR）功能保持完整。小梁置于含有ATP和不同浓度（150 - 400 nM）弱缓冲[Ca2+]的模拟细胞内溶液中。咖啡因诱导的挛缩幅度用作肌浆网钙含量的定量指标，并与心力衰竭的临床严重程度相关。然后将同一小梁暴露于含有 Triton-X100（1%）的溶液中，该溶液会破坏所有细胞膜，仅留下完整的肌丝。评估最大钙激活力（Cmax）和肌丝对钙的反应性。

结果

与患有缺血性心脏病（IHD）和中度心力衰竭（肺毛细血管楔压 - 20 mmHg，左心室射血分数> 20%，n = 6）的患者相比，患有缺血性心脏病（IHD）和严重心力衰竭（肺毛细血管楔压> 20 mmHg，射血分数< 15%，n = 8）的患者表现出较低的肌浆网Ca(2+)装载能力。扩张型心肌病（DCM）患者（n = 4）的肌浆网Ca(2+)装载能力低于两个IHD组中的任何一组。三组之间单位横截面积的肌丝力产生无显著差异。肌丝对Ca2+的反应性与心力衰竭的严重程度无关。