No effects of human ghrelin on cardiac function despite profound effects on body composition in a rat model of heart failure

No effects of human ghrelin on cardiac function despite profound effects on body composition in a rat model of heart failure
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DOI:
10.1016/j.ijcard.2008.06.094
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发表时间:
2009-11-01
影响因子:
3.5
通讯作者:
Springer, Jochen
Springer, Jochen
中科院分区:
医学2区
文献类型:
--
作者:
Akashi, Yoshihiro J.;Palus, Sandra;Springer, Jochen

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背景资料:Ghrelin,被观察到有治疗潜力的严重慢性心力衰竭(CHF)和心脏恶病质的基础上抗恶病质和cardioprotective effects.Methods:我们进行了两项研究,以评估人ghrelin对食物摄入量的影响,体重和身体成分,以及心脏功能在CHF大鼠模型。研究1(通过泵输注50或500 nmole/kg/d生长素释放肽)侧重于食物摄入和身体组成,研究2(通过皮下注射50或100 nmole/kg/d生长素释放肽(每日3次))侧重于心脏功能,因为在研究1中观察到缺乏心脏效应。在这两项研究中,心肌梗死是由LAD结扎引起的。在手术后第28天,将大鼠随机化并用ghrelin或安慰剂治疗4周。结果:在研究1中,用高剂量Ghrelin治疗的CHF大鼠显示体重增加(+25%,p < 0.05),而在研究2中,体重增加(+25%,p < 0.05),并且在研究3中,体重增加(+25%,p < 0.05),而在研究4中,体重增加(+25%,p < 0.05),而在研究4中,体重增加(+25%,p < 0.05)。
Background: Ghrelin, was observed to have treatment-potential for severe chronic heart failure (CHF) and cardiac cachexia based on anti-cachectic and cardio-protective effects.Methods: We performed two studies to assess the effects of human ghrelin on food intake, body weight and body composition, as well as heart function in a rat model of CHF. Study-1 (50 or 500 nmole/kg/d ghrelin by pump infusion) was focused on food intake and body composition, study-2 (50 or 100 nmole/kg/d ghrelin by subcutaneous injection (3-times daily) was focused on heart function due to a lack of cardiac effects observed in study-1. In both studies, myocardial infarction was induced by LAD ligation. On day 28 after surgery, rats were randomized and treated with ghrelin or placebo for 4 weeks. Food intake (study-1), body composition (NMR) cardiac function (echocardiography and invasive hemodynamics (study-2 only) were assessed.Results: In study-1, CHF rats treated with high dose ghrelin showed an increase in body weight (+25%, p