Document Detail

An in vitro rat diaphragmatic fatigue model induced by combined hypoxic and hypercapnic acidosis and the effect of salmeterol.
MedLine Citation:
PMID:  16310375     Owner:  NLM     Status:  MEDLINE    
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.
Xuanli Xu; Jianying Zhou; Qiuhuo Yang; Liben Fang; Qiangmin Xie; Yueliang Shen
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Publication Detail:
Type:  In Vitro; Journal Article     Date:  2005-11-28
Journal Detail:
Title:  Pharmacological research : the official journal of the Italian Pharmacological Society     Volume:  53     ISSN:  1043-6618     ISO Abbreviation:  Pharmacol. Res.     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2005-12-27     Completed Date:  2006-02-27     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8907422     Medline TA:  Pharmacol Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  171-6     Citation Subset:  IM    
Department of Respiratory Medicine, First Affiliated Hospital, Medical School of Zhejiang University, Hangzhou 310003, China.
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MeSH Terms
Acidosis / physiopathology*
Adrenergic beta-Agonists / pharmacology*
Albuterol / analogs & derivatives*,  pharmacology
Aminophylline / pharmacology
Anoxia / physiopathology*
Bronchodilator Agents / pharmacology
Diaphragm / drug effects,  physiology
Electric Stimulation
Hypercapnia / physiopathology*
Muscle Fatigue / drug effects,  physiology*
Muscle, Skeletal / drug effects,  physiology*
Rats, Sprague-Dawley
Reg. No./Substance:
0/Adrenergic beta-Agonists; 0/Bronchodilator Agents; 18559-94-9/Albuterol; 317-34-0/Aminophylline; 89365-50-4/salmeterol

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