Assessment of cardiac excitation-contraction coupling and effect of positive inctropic agent on Ca^<2+> regulating function of sarcoplasmic reticulum in heart failan

在心动过速性心力衰竭（HF）中，左室功能与左室肌肌浆网（SR）功能同时评估。首先，在心力衰竭中，米力酮或多巴酚丁胺的正性肌力作用减弱，而正性肌力作用得到很好的保留。在HF中观察到SR Ca^<2+>- atp酶对环AMP的敏感性增强，这可能与保持正肌变性有关。其次，HF患者通过SR （ryanodine receptor; RyR）的Ca^<2+>释放通道出现明显的Ca^<2+>异常泄漏，每RyR中FK结合蛋白的化学量减少。ryr结合的FKBP12.6的部分缺失似乎通过蛋白质构象改变诱导通道特性的不稳定性。这导致明显的Ca^<2+>泄漏，这可能是Ca^<2+>过载的原因，从而导致舒张功能障碍和收缩功能障碍。第三，在HF中，FKBP12.6与RyR之间相互作用的改变导致RyR通道性质的不稳定，并导致RyR的Ca^<2+>-释放功能受损。

In tachycardia-induced heart failure (HF), LV function was assessed in parallel with the function of sarcoplasmic reticulum (SR) taken from LV muscle. First, in HF, positive inotropic effects of milrinone or dobutamine were decreased, whereas positive lusitropic effects were well preserved. The enhancement of the sensitivity of SR Ca^<2+>-ATPase on cyclic AMP was observed in HF, which might be involved in this preservation of positive lusitropy. Second, a prominent abnormal Ca^<2+> leak occurred through the Ca^<2+> release channel of the SR (ryanodine receptor ; RyR) in HF, in which the stoichiometry of FK binding protein per RyR was decreased. This partial loss of RyR-bound FKBP12.6 seems to induce an instability in the channel's properties through a protein conformational change. This leads to a prominent Ca^<2+> leak, which is a possible cause of Ca^<2+> overload and hence diastolic dysfunction, as well as of systolic dysfunction. Third, in HF the altered interaction between FKBP12.6 and RyR induced an instability of RyR-channel properties and a resulting impairment of the Ca^<2+>-release function of RyR.