Heart Failure Research Group, Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
Circ Heart Fail. 2012 Nov;5(6):786-93. doi: 10.1161/CIRCHEARTFAILURE.112.968321. Epub 2012 Sep 26.
Despite adequate rate control, the combination of atrial fibrillation with heart failure (HF) has been shown, in a number of studies, to hasten HF progression. In this context, we aimed to test the hypothesis that an irregular ventricular rhythm causes an alteration in ventricular cardiomyocyte excitation-contraction coupling which contributes to the progression of HF.
We investigated the effects of electrical field stimulation (average frequency 2 Hz) in an irregular versus regular drive train pattern on the expression of calcium-handling genes and proteins in rat ventricular myocytes. The effect of rhythm on intracellular calcium transients was examined using Fura-2AM fluorescence spectroscopy. In conjunction, calcium-handling protein expression was examined in left ventricular samples obtained from end-stage HF patients, in patients with either persistent atrial fibrillation or sinus rhythm. Compared with regularly paced ventricular cardiomyocytes, in cells paced irregularly for 24 hours, there was a significant reduction in the expression of sarcoplasmic reticulum calcium (Ca(2+)) ATPase together with reduced serine-16 phosphorylation of phospholamban. These findings were accompanied by a 59% reduction (P<0.01) in the peak Ca2+ transient in irregulary paced myocytes compared with those with regular pacing. Consistent with these observations, we observed a 54% (P<0.05) decrease in sarcoplasmic reticulum Ca(2+)ATPase protein expression and an 85% (P<0.01) reduction in the extent of phosphorylation of phospholamban in the left ventricular myocardium of HF patients in atrial fibrillation compared with those in sinus rhythm.
Together, these data demonstrate that ventricular rhythmicity contributes significantly to excitation-contraction coupling by altering the expression and activity of key calcium-handling proteins. These data suggest that control of rhythm may be of benefit in patients with HF.
尽管已经进行了充分的心率控制，但在许多研究中，心房颤动与心力衰竭（HF）的合并已经表明会加速 HF 的进展。在这种情况下，我们旨在测试这样一个假设，即不规则的心室节律会导致心室肌细胞兴奋-收缩偶联的改变，从而促进 HF 的进展。
我们研究了在不规则与规则驱动列车模式下，电刺激（平均频率为 2 Hz）对大鼠心室肌细胞中钙处理基因和蛋白表达的影响。使用 Fura-2AM 荧光光谱法检查了节律对细胞内钙瞬变的影响。同时，在终末期 HF 患者、持续性心房颤动或窦性节律患者的左心室样本中检查了钙处理蛋白的表达。与规律起搏的心室肌细胞相比，在不规则起搏 24 小时的细胞中，肌浆网钙（Ca2+）ATP 酶的表达显著降低，同时磷蛋白的丝氨酸-16 磷酸化减少。这些发现伴随着不规则起搏心肌细胞中峰值 Ca2+瞬变减少 59%（P<0.01），与规律起搏相比。与这些观察结果一致，我们观察到在心房颤动的 HF 患者的左心室心肌中，肌浆网 Ca2+ATP 酶蛋白表达减少了 54%（P<0.05），磷蛋白的磷酸化减少了 85%（P<0.01），与窦性节律相比。
总之，这些数据表明，心室节律性通过改变关键钙处理蛋白的表达和活性，对兴奋-收缩偶联有重要贡献。这些数据表明，节律控制可能对 HF 患者有益。
