ABNORMALITIES IN INTRACELLULAR CALCIUM REGULATION AND CONTRACTILE FUNCTION IN MYOCARDIUM FROM DOGS WITH PACING-INDUCED HEART-FAILURE
ABNORMALITIES IN INTRACELLULAR CALCIUM REGULATION AND CONTRACTILE FUNCTION IN MYOCARDIUM FROM DOGS WITH PACING-INDUCED HEART-FAILURE
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DOI：
10.1172/jci115674
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发表时间：
1992-03-01
影响因子：
15.9
通讯作者：
MORGAN, JP
中科院分区：
文献类型：
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作者：
PERREAULT, CL;SHANNON, RP;MORGAN, JP
在清醒的慢性器械犬中，24 d的快速心室起搏诱导扩张型心肌病伴收缩和舒张功能障碍。 我们研究了15只对照犬（n = 32）和11只起搏诱导的心力衰竭犬（n = 26）的肌小梁的力学特性和细胞内钙（Ca（i）2+）瞬变。 在30 ℃下将肌肉拉伸至最大长度，并以0.33 Hz刺激;用[Ca 2 +]i指示剂水母发光蛋白加载一个子集（n = 17对照，n = 17肌病）。 在肌病肌肉中，峰值张力被抑制，即使在存在最大有效（即，16 mM）灌流液中的[Ca 2 +]。 然而，峰值[Ca 2 +]i相似（0.80 +/- 0.13 vs. 0.71 +/- 0.05 μ M; [Ca 2 +]o = 2.5 mM），表明Ca（i）2+可用性的降低不是收缩性降低的原因。 肌病组Ca（i）2+瞬变峰下降时间延长，与等长收缩和舒张时间延长相关。 然而，两组的舒张末期[Ca 2 +]i相似（0.29 +/- 0.05 vs. 0.31 +/- 0.02 μ M），表明在肌病心脏中可以维持Ca（i）2+稳态。 与对照组相比，肌病肌肉对米力农的变力性反应被抑制。 然而，当cAMP的生产刺激预处理与毛喉素，肌病肌肉米力农的反应得到改善。 我们的研究结果提供了直接的证据，异常[Ca 2 +]i处理是一个重要的原因，收缩功能障碍的狗起搏诱导的心力衰竭，并建议，缺乏生产的cAMP可能是这些变化的重要原因兴奋收缩耦合。
24 d of rapid ventricular pacing induced dilated cardiomyopathy with both systolic and diastolic dysfunction in conscious, chronically instrumented dogs. We studied mechanical properties and intracellular calcium (Ca(i)2+) transients of trabeculae carneae isolated from 15 control dogs (n = 32) and 11 dogs with pacing-induced cardiac failure (n = 26). Muscles were stretched to maximum length at 30-degrees-C and stimulated at 0.33 Hz; a subset (n = 17 control, n = 17 myopathic) was loaded with the [Ca2+]i indicator aequorin. Peak tension was depressed in the myopathic muscles, even in the presence of maximally effective (i.e., 16 mM) [Ca2+] in the perfusate. However, peak [Ca2+]i was similar (0.80 +/- 0.13 vs. 0.71 +/- 0.05-mu-M; [Ca2+]o = 2.5 mM), suggesting that a decrease in Ca(i)2+ availability was not responsible for the decreased contractility. The time for decline from the peak of the Ca(i)2+ transient was prolonged in the myopathic group, which correlated with prolongation of isometric contraction and relaxation. However, similar end-diastolic [Ca2+]i was achieved in both groups (0.29 +/- 0.05 vs. 0.31 +/- 0.02-mu-M), indicating that Ca(i)2+ homeostasis can be maintained in myopathic hearts. The inotropic response of the myopathic muscles to milrinone was depressed compared with the controls. However, when cAMP production was stimulated by pretreatment with forskolin, the response of the myopathic muscles to milrinone was improved. Our findings provide direct evidence that abnormal [Ca2+]i handling is an important cause of contractile dysfunction in dogs with pacing-induced heart failure and suggest that deficient production of cAMP may be an important cause of these changes in excitation-contraction coupling.