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Danjo, Wataru Department of Emergency Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Fujimura, Naoyuki Department of Emergency Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Ujike, Yoshihito Department of Emergency Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
We investigated the effects of pentoxifylline (PTX) on endotoxin-induced diaphragmatic dysfunction in vitro. Seventy-two rats were divided into 3 groups: a group in which endotoxin (20 mg/kg) was injected intraperitoneally (endotoxin-group), a group in which PTX (100 mg/kg) was injected intraperitoneally 30 min before injection of endotoxin (endotoxin-PTX group), and a group in which only saline was given (sham group). Left hemidiaphragms were removed 4 h after injection of endotoxin. We evaluated the diaphragmatic contractility by twitch characteristics and force-frequency curves in vitro. We measured serum TNF-alpha concentrations, diaphragm malondialdehyde (MDA) levels (an index of oxygen-derived free radical-mediated lipid peroxidation), and diaphragm cAMP concentrations. Diaphragmatic force generation capacity was signifi cantly reduced after injection of endotoxin. Serum TNF-alpha concentrations and diaphragmatic MDA levels were significantly elevated after injection of endotoxin. PTX administration significantly improved diaphragmatic contractility and prevented the elevation in TNF-alpha concentrations and MDA levels after injection of endotoxin. There were no significant changes in the diaphragm cAMP concentrations among the 3 groups. These results demonstrated that PTX administration prevented endotoxin-induced diaphragmatic dysfunction without changing diaphragm muscle cAMP concentrations. The protective effects of PTX against endotoxininduced diaphragmatic contractile deterioration might be caused by attenuating TNF-alpha-mediated oxygen-derived free radical production.
Acta Medica Okayama
Okayama University Medical School
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