RELATIONSHIP BETWEEN INTRACELLULAR CALCIUM AND CONTRACTILE-FORCE IN STUNNED MYOCARDIUM - DIRECT EVIDENCE FOR DECREASED MYOFILAMENT CA2+ RESPONSIVENESS AND ALTERED DIASTOLIC FUNCTION IN INTACT VENTRICULAR MUSCLE
RELATIONSHIP BETWEEN INTRACELLULAR CALCIUM AND CONTRACTILE-FORCE IN STUNNED MYOCARDIUM - DIRECT EVIDENCE FOR DECREASED MYOFILAMENT CA2+ RESPONSIVENESS AND ALTERED DIASTOLIC FUNCTION IN INTACT VENTRICULAR MUSCLE
复制标题
DOI：
10.1161/01.res.76.6.1036
复制
发表时间：
1995-06-01
影响因子：
20.1
通讯作者：
MARBAN, E
中科院分区：
文献类型：
--
作者：
GAO, WD;ATAR, D;MARBAN, E
为了阐明击晕心肌中兴奋-收缩耦合的异常，我们测量了对照或击晕（20 分钟缺血，然后在 37°C 下 20 分钟复流）大鼠心脏的加载有 fura 2 的薄心室小梁中的 [Ca2+](i) 和力。在任何给定的[Ca2+](o)下，震惊小梁中的力发展显着低于对照小梁。相反，两组之间的 Ca2+ 瞬变幅度没有差异。通过在兰尼碱存在下的强直作用评估稳态力-[Ca2+](i) 关系，揭示了最大 Ca2+ 激活力的降低和致晕小梁中 50% 激活所需的 [Ca2+](i) 的增加。缺血后心肌还表现出舒张期舒张速率加快，这并不是由于 Ca2+ 瞬时衰减速率的变化所致。心肌原纤维定量模型中附着的横桥的不稳定准确地再现了震惊表型的显着收缩期和舒张期特征，表明细丝的异常。作为对 [Ca2+](o) 超生理增加的反应，震惊小梁中的舒张压 [Ca2+](i) 和舒张张力比对照组增加更多，并频繁发生后收缩。这种新颖的实验模型进一步支持了兴奋-收缩耦合的主要损伤位于收缩蛋白水平的假设。对钙超载敏感性增强的发现有助于合理化在强烈的正性肌力刺激期间顿顿心肌的功能恶化，并且还表明顿顿心肌可能是引发心律失常的有利基质。
To elucidate the abnormalities of excitation-contraction coupling in stunned myocardium, we measured [Ca2+](i) and force in thin fura 2-loaded ventricular trabeculae from control or stunned (20 minutes ischemia followed by 20 minutes reflow at 37 degrees C) rat hearts. At any given [Ca2+](o), force development was significantly lower in the stunned trabeculae than in control trabeculae. In contrast, there was no difference in the amplitude of Ca2+ transients between the two groups. The steady state force-[Ca2+](i) relationship, assessed by tetanization in the presence of ryanodine, revealed both a decrease in maximal Ca2+-activated force and an increase in the [Ca2+](i) required for 50% activation in stunned trabeculae. Postischemic myocardium also exhibited an accelerated rate of diastolic relaxation that was not due to changes in the rate of Ca2+ transient decay. Destabilization of attached cross-bridges in a quantitative model of cardiac myofibrils accurately reproduced the salient systolic and diastolic features of the stunned phenotype, suggesting an abnormality of the thin filaments. In response to supraphysiological increases in [Ca2+](o), diastolic [Ca2+](i) and diastolic tone increased much more in stunned trabeculae than in controls, with the frequent occurrence of aftercontractions. This novel experimental model lends further support to the hypothesis that the primary lesion of excitation-contraction coupling resides at the level of the contractile proteins. The finding of enhanced susceptibility to calcium overload helps to rationalize the functional deterioration of stunned myocardium during intense inotropic stimulation and additionally suggests that stunned myocardium may represent a favorable substrate for triggered arrhythmias.