Institute of Cardiovascular & Medical Sciences, West Medical Building, University of Glasgow, G12 8QQ, UK.
Circ Res. 2012 Jun 8;110(12):1618-27. doi: 10.1161/CIRCRESAHA.111.262337. Epub 2012 May 3.
The extent to which sarcoplasmic reticulum Ca(2+)ATPase (SERCA) activity alone determines left ventricular (LV) pump function is unknown.
To correlate SERCA activity with hemodynamic function of rabbit LV during thapsigargin perfusion.
Isolated rabbit hearts were perfused in working heart configuration, and LV pump function was assessed using a pressure-volume catheter. Rapid and complete (>95%) inhibition of SERCA was associated with a moderate decrease in cardiac function (to 70%-85% of control). Further decrease in cardiac function to 50%-75% of control occurred over the next ≈ 30 minutes despite no detectable further inhibition of SERCA activity. Analysis of the 20 seconds prior to pump failure revealed a rapid decrease in end diastolic volume. Intermediate levels of SERCA function (≈ 50% of control) had only minor hemodynamic effects. Parallel experiments in field-stimulated isolated ventricular cardiomyocytes monitored intracellular Ca(2+) and cell shortening. On perfusion with thapsigargin, Ca(2+) transient amplitude and cell shortening fell to ≈ 70% of control followed by increased diastolic Ca(2+) concentration and diastolic cell shortening to achieve a new steady state.
The relationship between SERCA activity and LV function in the rabbit is highly nonlinear. In the short term, only moderate effects on LV pump function were observed despite almost complete (>95%) reduction in SERCA activity. The terminal decline of function was associated with sudden sustained increase in diastolic tone comparable to the sustained contraction observed in isolated cardiomyocytes. Secondary increases of intracellular Ca(2+) and Na(+) following complete SERCA inhibition eventually limit contractile function and precipitate LV pump failure.
肌浆网 Ca2+-ATP 酶（SERCA）活性单独决定左心室（LV）泵功能的程度尚不清楚。
在 thapsigargin 灌注期间，将 SERCA 活性与兔 LV 的血液动力学功能相关联。
采用工作心脏构型对分离的兔心进行灌注，并使用压力-容积导管评估 LV 泵功能。快速且完全（>95%）抑制 SERCA 与心脏功能中度降低（降至对照的 70%-85%）相关。尽管 SERCA 活性无进一步检测到的抑制，但在接下来的 ≈30 分钟内，心脏功能进一步下降至对照的 50%-75%。在泵衰竭之前的 20 秒分析显示舒张末期容积迅速下降。中间水平的 SERCA 功能（≈对照的 50%）仅有轻微的血液动力学影响。在受刺激的分离心室心肌细胞的平行实验中监测细胞内 Ca2+和细胞缩短。在用 thapsigargin 灌注时，Ca2+瞬变幅度和细胞缩短降至对照的 ≈70%，随后舒张 Ca2+浓度和舒张细胞缩短增加，达到新的稳定状态。
兔的 SERCA 活性与 LV 功能之间的关系高度非线性。在短期内，尽管 SERCA 活性几乎完全（>95%）降低，但仅观察到 LV 泵功能的中度影响。功能的终末下降与舒张张力的突然持续增加相关，类似于在分离的心肌细胞中观察到的持续收缩。完全抑制 SERCA 后细胞内 Ca2+和 Na+的继发增加最终限制收缩功能并引发 LV 泵衰竭。
