Positive inotropic effect of insulin-like growth factor-1 on normal and failing cardiac myocytes

Positive inotropic effect of insulin-like growth factor-1 on normal and failing cardiac myocytes
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DOI:
10.1016/s0008-6363(99)00058-9
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发表时间:
1999-07-01
影响因子:
10.8
通讯作者:
Takeshita, A
Takeshita, A
中科院分区:
医学1区
文献类型:
--
作者:
Kinugawa, S;Tsutsui, H;Takeshita, A

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目的:急性给予生长激素(GH)或胰岛素样生长因子-1 (IGF-1)可改善心脏功能,可能有助于GH治疗心力衰竭(HF)的有益作用。生长激素可以诱导IGF-1的产生,因此生长激素的作用可能是通过其诱导IGF-1来介导的。然而,这些作用尚未在衰竭的心脏中得到证实,生长激素或igf -1诱导的肌力作用的细胞基础仍不清楚。我们研究了生长激素和IGF-1对正常和衰竭肌细胞收缩功能和细胞内钙([Ca2+]i)稳态的直接影响。方法:为了确定GH和IGF-1是否对心肌收缩力有直接影响,以及GH/IGF-1诱导的作用是否是Ca2+活化变化的结果,同时测量了从正常和快速起搏诱导的HF犬分离的左心室肌细胞制剂中细胞缩短和[Ca2+](i)瞬态的变化。结果:心肌细胞基础缩短减少64% (p
Objective: The acute administration of growth hormone (GH) or insulin-like growth factor-1 (IGF-1) improves cardiac performance, possibly contributing to the beneficial effects of GH therapy on heart failure (HF). GH can induce the production of IGF-1 and thus the actions of GH may be mediated through its IGF-1 induction. However, these effects have not yet been demonstrated in failing hearts and the cellular basis of GH or IGF-1-induced inotropic effects remains unknown. We examined the direct effects of GH and IGF-1 on the contractile function and intracellular calcium ([Ca2+]i) homeostasis in normal and failing myocytes. Methods: To determine whether GH and IGF-1 have a direct effect on myocardial contractility and whether the GH/IGF-1-induced effect was the results of changes in Ca2+-activation, cell shortening and [Ca2+](i) transient were simultaneously measured in the left ventricular myocyte preparations, isolated from normal and rapid pacing-induced HF dogs. Results: Basal shortening of HF myocytes was reduced by 64% (p