Tulobuterol Patch Maintains Diaphragm Muscle Contractility for Over Twenty-four Hours in a Mouse Model of Sepsis
Tulobuterol Patch Maintains Diaphragm Muscle Contractility for Over Twenty-four Hours in a Mouse Model of Sepsis
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DOI：
10.1620/tjem.218.271
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发表时间：
2009-08-01
影响因子：
2.2
通讯作者：
Miura, Masahito
中科院分区：
文献类型：
--
作者：
Shindoh, Chiyohiko;Murakami, Yoshie;Miura, Masahito
妥洛特罗是一种拟交感神经药物，用作透皮贴剂，可增加正常的膈肌力量。由于膈肌无力（即收缩减少）是支气管哮喘和脓毒症的特征，我们研究了妥洛特罗对内毒素处理小鼠制备的膈肌收缩性的体外和体内影响。我们使用未处理或处理的膈肌在大肠杆菌内毒素（20 mg/kg）给药后0（E0）和4（E4）小时测量力-频率曲线和抽搐动力学的收缩参数。E4膈肌的力-频曲线较E0膈肌下降（p < 0.001）。将E4膈肌在含有10（-7）或10（-5）M浓度的妥洛特罗的器官缓冲液中孵育1小时（体外）。10（-7）（p < 0.01）或10（-5）M（p < 0.001）妥洛特罗浓度的力-频率曲线与无妥洛特罗的力-频率曲线相比显著上移，表明妥洛特罗可以恢复内毒素降低的膈肌收缩力。在体内治疗中，在透皮妥洛特罗治疗后0、12和24 h分析E0和E4膈肌。E0和E4膈肌在3个时间点的力-频率曲线无明显变化，表明妥洛特罗贴剂恢复了肌肉的收缩性。因此，在给予内毒素4 h期间，妥洛特罗贴剂维持膈肌收缩性超过24 h。我们认为，这种治疗支气管哮喘可以防止吸入的室内灰尘中所含的内毒素。
Tulobuterol, a sympathomimetic drug used as a transdermal patch, increases normal diaphragm muscle strength. Because diaphragm muscle weakness (i.e. decrease of contraction) is a feature of bronchial asthma and sepsis, we examined the in vitro and in vivo effects of tulobuterol on the contractility of diaphragm muscles prepared from mice treated with endotoxin. We measured contractile parameters of force-frequency curves and twitch kinetics using untreated or treated diaphragm muscles at 0 (E0) and 4 (E4) hours after E coli endotoxin (20 mg/kg) administration. The force-frequency curve of E4 diaphragm muscle was decreased from that of E0 diaphragm muscle (p < 0.001). E4 diaphragm muscle was incubated in an organ buffer containing 10(-7) or 10(-5) M concentrations of tulobuterol for 1 h (in vitro). The force-frequency curves of both 10(-7) (p < 0.01) or 10(-5) M (p < 0.001) tulobuterol concentrations shifted significantly upward from those of no tulobuterol, indicating that tulobuterol can recover the diaphragm muscle contractility that was decreased by endotoxin. In the in vivo treatment, E0 and E4 diaphragm muscles were analyzed at 0, 12, and 24 h after transdermal tulobuterol treatment. The force-frequency curves of E0 and E4 diaphragm muscles at three time points were not significantly changed each other, indicating that tulobuterol patch restores the muscle contractility. Thus, diaphragm muscle contractility was maintained during 4 h of endotoxin administration with tulobuterol patch for over 24 h. We suggest that this treatment of bronchial asthma may protect against endotoxin contained in inhaled house dust.