Birkeland Jon Arne, Sejersted Ole M, Taraldsen Tore, Sjaastad Ivar
Institute for Experimental Medical Research, Ullevål University Hospital, University of Oslo, Oslo, Norway.
Scand Cardiovasc J. 2005 Apr;39(1-2):13-23. doi: 10.1080/14017430410004632.
Systolic heart failure may be due to too few cardiomyocytes, or to reduced contractile function of the heart cells. In the latter situation the myocardial function is impaired and this condition is called myocardial failure. The pathophysiological mechanism behind this cellular defect is not known, but Ca2+ handling is altered. Although the most important trigger of sarcoplasmatic reticulum (SR) Ca2+ release, the L-type Ca2+ current, seems to be unaltered, SR Ca2+ load is reduced in human heart failure. This could explain the reduced contractility observed in failing hearts. Three possible mechanisms have been suggested to explain the reduction in SR Ca2+ load. They are leak through the SR Ca2+ release channel (RyR), impaired SR Ca2+ ATPase (SERCA) function and increased Na+/Ca2+-exchanger (NCX) function. Leak through RyR is not consistently found. Increased NCX function is probably secondary to a change in Ca2+ handling, and thus not a primary mechanism, but blockade of the NCX might have therapeutic potential. Reduced SERCA function is probably a primary mechanism for the observed systolic dysfunction, and further insight is to be gained through studies in genetically modified models.
收缩性心力衰竭可能是由于心肌细胞数量过少，或者是由于心脏细胞的收缩功能降低。在后一种情况下，心肌功能受损，这种情况称为心肌衰竭。这种细胞缺陷背后的病理生理机制尚不清楚，但钙离子处理发生了改变。尽管肌浆网（SR）钙离子释放的最重要触发因素，即L型钙离子电流似乎未发生改变，但在人类心力衰竭中，SR钙离子负荷降低。这可以解释在衰竭心脏中观察到的收缩力降低。已经提出了三种可能的机制来解释SR钙离子负荷的降低。它们是通过SR钙离子释放通道（RyR）的渗漏、SR钙离子ATP酶（SERCA）功能受损以及钠/钙交换体（NCX）功能增强。通过RyR的渗漏并非始终存在。NCX功能增强可能继发于钙离子处理的变化，因此不是主要机制，但阻断NCX可能具有治疗潜力。SERCA功能降低可能是观察到的收缩功能障碍的主要机制，通过对基因修饰模型的研究将获得进一步的认识。
