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A selective beta2-adrenergic agonist, terbutaline, improves sepsis-induced diaphragmatic dysfunction in the rat

机译：选择性β2-肾上腺素能激动剂特布他林可改善脓毒症诱发的diaphragm肌功能障碍

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Background: Sepsis causes diaphragmatic dysfunction, which can lead to the development of respiratory failure. We previously reported that isoproterenol, non-selective beta-adrenergic agonist, improved contractility of the diaphragm in a septic rat model. Since beta(2)-adrenoceptor agonists are widely used in the treatment of chronic respiratory disease, we investigated the effect of terbutaline, a selective beta(2)-adrenergic agonist, on contractility of the septic rat diaphragm and the contribution of intracellular Ca2+ to the effect of terbutaline in vitro. Methods: Forty-eight rats were divided into a sham group (in which sham laparotomy was performed) and a CLP group (in which peritonitis was induced by cecal ligation and perforation). The left hemidiaphragm was removed at 16 h after the operation. The effect of terbutaline (10(-6) M) on contractility of the diaphragm was assessed by twitch characteristics (twitch tension, contraction time and contraction velocity) and force-frequency relationship. In addition, to investigate the role of calcium ions in the effect of terbutaline on contractility of the diaphragm, contractility of the diaphragm was assessed after the pre-incubation of the diaphragm with methoxy-verapamil (10(-5) M), Ca2+-free Krebs-Ringer's solution buffered with 2 mM of ethylene glycol tetra-acetic acid (EGTA), and ryanodine (10(-6) M). Results: Terbutaline significantly improved twitch characteristics and force-frequency relationship of the diaphragm in the CLP group (P < 0.01). Incubation with methoxy-verapamil or calcium-free solution with EGTA did not show any changes in the inotropic effect of terbutaline in the CLP group. However, incubation with ryanodine completely abolished the inotropic effect of terbutaline in the CLP group. Conclusions: The present study demonstrated that terbutaline increased contractility of the diaphragm in the septic rats. Since this inotropic effect was abolished by ryanodine administration, calcium release from the sarcoplasmic reticulum may contribute to the terbutaline-induced improvement in dysfunction of the septic diaphragm. (c) 2006 Elsevier Inc. All rights reserved.
机译：背景：败血症引起diaphragm肌功能障碍，可导致呼吸衰竭的发展。我们先前曾报道，在脓毒症大鼠模型中，异丙肾上腺素（非选择性β-肾上腺素能激动剂）改善了隔膜的收缩性。由于β（2）-肾上腺素受体激动剂被广泛用于治疗慢性呼吸道疾病，因此我们研究了选择性的β（2）-肾上腺素能激动剂特布他林对脓毒症大鼠diaphragm肌的收缩性和细胞内Ca2 +的贡献。特布他林的体外作用。方法：将48只大鼠分为假手术组（进行假剖腹手术）和CLP组（由盲肠结扎和穿孔诱发腹膜炎）。术后16 h取出左半ia。通过抽搐特性（抽搐张力，收缩时间和收缩速度）和力-频率关系评估了特布他林（10（-6）M）对隔膜收缩性的影响。另外，为了研究钙离子在特布他林对隔膜收缩性的影响中的作用，在将隔膜与甲氧基维拉帕米（10（-5）M），Ca2 +-一起预孵育后评估了隔膜的收缩性用2 mM乙二醇四乙酸（EGTA）和ryanodine（10（-6）M）缓冲的游离Krebs-Ringer溶液。结果：特布他林显着改善了CLP组的抽搐特性和隔膜的力频关系（P <0.01）。在CLP组中，用甲氧基维拉帕米或无钙溶液与EGTA一起温育并未显示特布他林的正性肌力作用有任何变化。但是，在CLP组中，与ryanodine孵育完全消除了特布他林的正性肌力作用。结论：本研究表明特布他林可增加脓毒症大鼠the肌的收缩力。由于利诺丁给药消除了这种肌力作用，因此从肌质网释放的钙可能有助于特布他林引起的化脓性隔膜功能障碍的改善。 （c）2006 Elsevier Inc.保留所有权利。

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