Characterization of calcium transients of separated myocytes from failing heart

目的与方法：细胞内游离钙离子在心肌细胞兴奋收缩偶联中发挥重要作用，从而调节心脏功能。我们和其他人最近的研究发现，心脏衰竭时钙代谢异常。为了研究心力衰竭时钙离子转运的特点，我们采用野百合碱诱导的右室肥厚合并心力衰竭模型。用朗宁多夫装置分离右室心肌细胞后，分离Fura-2/AM。结果：正常对照心脏的钙瞬变峰比(PR)和静息比(PR)随刺激频率的增加而增加，并净增加幅度(PR-PR)。心衰时钙-T的PR和PR也随着刺激频率的增加而增加。心衰时，钙-T波幅随刺激频率的增加而降低。心衰心肌细胞在5赫兹刺激时，RR显著增加，但无幅度。心力衰竭时Ca-T的这些变化与心力衰竭的严重程度有很好的相关性。正常心脏和衰竭心脏的Ca-T随刺激频率的变化是可逆的。结论：心力衰竭患者的CA-T，尤其是RR和波幅随刺激频率的增加而改变。也就是说，随着心力衰竭患者心率的增加，细胞内游离钙释放和再摄取机制明显紊乱，这可能导致进一步的收缩和舒张期功能障碍。虽然心率依赖性异常的确切机制尚需阐明，但心力衰竭时的心率控制对于维持和/或改善心力衰竭时的心功能是重要的。

Objectives & Methods : Intarcellular free calcium ion plays important roles in excitation-contraction coupling in cardiac myocytes, thereby regulating cardiac function. Recent studies of ours and others have revealed abnormal calcium handling in failing heart. To examine characteristics of calcium handling in failing heart, we used monocrotaline-induced right ventricular hypertrophy model with heart failure. After cardiac myocytes were separated from RV by Langendorff apparatus, Fura-2/AM was leaed. Calcium transients (Ca-T) were measured by changing stimulatory frequency from 0.5Hz to 5Hz.Results : Peak ratio (PR) and resting ratio (PR) of Ca-T in control normal heart increased with the increase in stimulatory frequency, with net increase in amplirude (PR-PR) . PR and PR of Ca-T in failing heart also increased as the stimulatory frequency increased. However, amplitude of Ca-T in failing heart decreased with the increase in stimulatory frequency. Remarkable increase in RR with no amplitude was observed when the myocytes from failing heart were stimulated at 5 Hz. These changes in Ca-T in failing heart correlated well with the severity of heart failure. The changes in Ca-T with changes in stimulatory frequency in normal and failing heart were reversible. Conclusions : Ca-T,especially, RR and amplitude, in failing heart alter with increase in stimulatory frequency. That is intracellular free calcium release and reuptake mechanisms were disturbed remarkably with the increase in heart rate in failing heart, which may result in further systolic and diastolic dysfunction. Although exact mechanism for heart rate-dependent abnormalities should be elucidated, heart rate control in failing heart is important to maintain and/or improve cardiac function in failing heart.