Congestive heart failure: role of cross-bridge cycle kinetics.
Congestive heart failure: role of cross-bridge cycle kinetics.
复制标题
充血性心力衰竭：跨桥循环动力学的作用。
DOI：
10.1016/s0008-6363(98)00247-8
复制
发表时间：
1998
影响因子：
10.8
通讯作者：
deTombe,PP
中科院分区：
文献类型：
--
作者：
deTombe,PP
心脏在循环中的基本作用，动物研究表明，钙系统抑制是泵血量，这正是实验性心力衰竭的反应[7-10]。与身体组织的需求相匹配，然而，在足够的灌注下保持收缩力的能力。这一任务必须在细胞质钙浓度仅是中断的一个方面且在所有条件下完成。因此，心脏收缩功能。在正常情况下，为了泵送一定体积的血液，心输出量是处于压力下的血液，必须由心肌丝产生通过大量调节反馈系统控制的与冲程功相当的能量总量，所述心肌丝以不同的时间常数操作，所述时间常数在称为“化学机械转换”的过程中的时间范围内，几乎是瞬时的。（心率、收缩状态、静脉收缩，其中通过主动循环交叉电容的ATP水解）、中间体（液体和盐保留）和桥被转换成机械能。长期（心脏重塑）率。在病理条件下，当心肌功能受到抑制时，能量转换反映在功率条件下，心脏的心脏发电能力[11]。这两种输出都是通过增加调节参数来维持的，调节参数是肌节反馈信号的基本特性。然而，如果与力-速度关系直接相关的心肌功能继续下降，最终会达到这样一个点，即正如本世纪初所证明的那样，随着AV Hill工作的增加，种子心输出量不再增加[12]。尽管关于反馈信号存在一些争论。此时，所有调节心血管-机械-能量联系的确切性质的大反馈控制系统已被耗尽，心肌[13]，毫无疑问，跨桥心力衰竭综合征的临床表现增强[1]。循环在确定动力学中起着不可或缺的作用。心力衰竭的症状是由于心脏的反应特性。然而，迄今为止，只有一项研究报道了泵功能，但综合征的根本原因是失效的同种异体的动态机械特性抑制了内在心肌功能[2]。在过去的十年里，有许多针对组织的研究。在对皮肤心肌的研究中，Hajjar和在阐明细胞Gwathmey [14]的基础机制时发现，在人类心力衰竭中观察到的最大收缩功能障碍减少了40%，未加载缩短速度和最小动态刚度-[3]。总的来说，这些研究表明，而不是结论频率。这两个参数都反映了在终末期内在跨桥循环速率的钙稳态改变。Ruf et Human Heart Failure的报告。以确定是否肌丝。[15]来自弗赖堡的Holubarsch小组，在该功能受到影响的情况下，研究人员已经测量了心血管研究的问题，两者都证实了等长收缩力产生之间的关系，并将这些观察结果扩展到完整的分离心肌和钡挛缩期间完整或皮肤分离的钙浓度。正如Hajjar和人类心肌的工作[4-6]。不幸的是，Gwathmey [14]的结果，这些研究人员发现40%的减少这些研究一直不一致，显示要么没有...
The fundamental role of the heart in the circulatory the animal studies that have shown depressed calcium system is to pump an amount of blood that is precisely responsiveness in experimental heart failure [7–10]. matched to the requirements of the body’s tissues for However, the ability to maintain contractile force at a adequate perfusion. This task must be accomplished with- given cytosolic calcium concentration is but one aspect of out interruption and under all conditions. Because of this, cardiac contractile function. In order to pump a volume of and under normal conditions, cardiac output is tightly blood under pressure, a total amount of energy equivalent controlled via a multitude of regulatory feedback systems to stroke work must be generated by the cardiac myofilathat operate with different time constants that range from ments in a process termed ‘chemo-mechanical transducvirtually instantaneous (heart rate, contractile state, venous tion’, in which ATP hydrolysis by active cycling crosscapacitance), intermediate (fluid and salt retention) and bridges is converted into mechanical energy. The rate at long term (cardiac remodeling). Under pathological con- which energy is converted is reflected in the powerditions when myocardial function is depressed, cardiac generating capacity of the heart [11]. Both of these output is maintained by an increase in the regulatory parameters are fundamental properties of the sarcomere feedback signals. However, if myocardial function con- that are directly linked to the force–velocity relationship, tinues to decline, a point is ultimately reached at which as was demonstrated early in this century by the seminal cardiac output no longer increases upon an increase in the work of AV Hill [12]. Although there is some debate as to feedback signals. At this point, all regulatory cardiovascu- the exact nature of the mechanical–energetic link in lar feedback control systems have been exhausted and the cardiac muscle [13], there is no doubt that cross-bridge clinical syndrome of heart failure ensues [1]. cycling plays an integral role in determining the dynamic The symptoms of heart failure are due to the responses properties of the heart. of the peripheral cardiovascular system to reduced cardiac To date, however, only one study has been reported in pump function, yet the underlying cause of the syndrome which the dynamic mechanical properties of failing isolies in the depression of intrinsic myocardial function [2]. lated human myocardium is compared to non-failing Therehavebeennumerousstudiesinthelastdecadeaimed tissue. In work on skinned myocardium, Hajjar and at elucidating the mechanisms that underlie the cellular Gwathmey [14] found 40% reductions in the maximum contractile dysfunction that is seen in human heart failure unloaded shortening velocity and minimum dynamic stiff-[3]. Collectively, these studies have shown, rather conclu- ness frequency. Both of these parameters are reflections of sively, that calcium homeostasis is altered in end-stage the intrinsic cross-bridge cycling rate. The report by Ruf et human heart failure. To determine whether myofilament al.[15] from the group of Holubarsch in Freiburg, in this function is affected, investigators have measured the issue of Cardiovascular Research, both confirms and relationship between isometric contractile force generation extends these observations to intact isolated myocardium and calcium concentration in intact or skinned isolated during a barium contracture. As in the work of Hajjar and human myocardium [4–6]. Unfortunately, the results of Gwathmey [14], these investigators find a 40% reduction these studies have been inconsistent, showing either no in …