title: An in vitro rat diaphragmatic fatigue model induced by combined hypoxic and hypercapnic acidosis and the effect of salmeterol.
abstract: Hypoxia or hypercapnia impairs diaphragmatic contractility and induces fatigue. However, little is known about the combined effect of hypoxic and hypercapnic acidosis (HHA) on diaphragmatic fatigue. In this study, a gas mixture (21% O2, 12% CO2 and 67% N2) was used to produce HHA-induced rat diaphragmatic fatigue. Force-frequency relationships and twitch characteristics including peak twitch tension (PTT), time to peak tension (TPT), half relaxation time (1/2RT), maintaining tension (MT) and direct-muscle-stimulation tension (MST) were measured in diaphragm preparations from male SD rats. The HHA gas mixture attenuated force at all frequencies (5-120 Hz) and decreased PTT, MT and MST significantly. Aminophylline, a positive control drug, blocked the negative inotropic effect of HHA in a dose-dependent manner. Moreover, salmeterol, a long-acting beta2-adrenoceptor agonist, inhibited the harmful effect of HHA at high frequencies (40-120 Hz), but without effect on MT and MST. These results suggest that an in vitro HHA-induced rat diaphragmatic fatigue model could be established by aerating with the gas mixture, which may be an optimal model to screen effective drugs for diaphragmatic fatigue. Furthermore, salmeterol may play a protective role in HHA-induced impairment.
authors.affiliation: Department of Respiratory Medicine, First Affiliated Hospital, Medical School of Zhejiang University, Hangzhou 310003, China. hangzhouxx1@hotmail.com
authors.forename: Xuanli
authors.initials: X
authors.lastname: Xu
authors.forename: Jianying
authors.initials: J
authors.lastname: Zhou
authors.forename: Qiuhuo
authors.initials: Q
authors.lastname: Yang
authors.forename: Liben
authors.initials: L
authors.lastname: Fang
authors.forename: Qiangmin
authors.initials: Q
authors.lastname: Xie
authors.forename: Yueliang
authors.initials: Y
authors.lastname: Shen
mesh_terms: D000138:Acidosis / Q000503:physiopathology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D001993:Bronchodilator Agents / Q000494:pharmacology; D003964:Diaphragm / Q000187:drug effects / Q000502:physiology; D004558:Electric Stimulation; D006935:Hypercapnia / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D018763:Muscle Fatigue / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068299:Salmeterol Xinafoate
chemical_list: D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D000628:Aminophylline; D000068299:Salmeterol Xinafoate; D000420:Albuterol