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Characterization of calcium transients of separated myocytes from failing heart

衰竭心脏中分离的心肌细胞的钙瞬变特征

基本信息

批准号：
04670536
负责人：
HONDA Masaaki
金额：
$ 1.34万
依托单位：
Shimane Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04670536/
关键词：
Heart failure Calcium Transients Monocrotaline Cardiac hypertrophy Heart rate dependency heart failure calcium transients adrenergic response single myocytes

项目摘要

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.

目的和方法：细胞内游离钙离子在心肌细胞兴奋-收缩偶联中起重要作用，从而调节心脏功能。我们和其他人最近的研究揭示了在衰竭的心脏中钙的异常处理。为了研究心力衰竭时钙处理的特点，我们采用野百合碱诱导的心力衰竭右心室肥厚模型。用Langendorff分离器分离右心室心肌细胞后，分离Fura-2/AM。结果：正常对照心脏Ca-T峰值比（PR）和静息比（PR）均随刺激频率的增加而增加，振幅净增加（PR-PR）。心衰组Ca-T的PR和PR也随刺激频率的增加而增加。而衰竭心脏Ca-T振幅则随刺激频率的增加而降低。以5 Hz频率刺激心衰心肌细胞，RR无振幅，但明显增加。心衰时Ca-T的变化与心衰的严重程度密切相关。正常和衰竭心脏Ca-T随刺激频率的变化是可逆的。结论：心衰时Ca-T，尤其是RR和振幅随刺激频率的增加而改变。即心衰时随着心率的增加，细胞内游离钙的释放和再摄取机制受到明显干扰，可能导致进一步的收缩和舒张功能障碍。尽管心率依赖性异常的确切机制尚待阐明，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非常重要。