Effect of pentoxifylline on diaphragmatic contractility in septic rats.
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.
Danjo
Wataru
W
Department of Emergency Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan. wataru.danjo@doc.city.sapporo.jp
Fujimura
Naoyuki
N
Ujike
Yoshihito
Y
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D003964:Diaphragm / Q000187:drug effects / Q000502:physiology; D004731:Endotoxins / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005609:Free Radicals / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D010431:Pentoxifylline / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000139:chemically induced / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology*
D004731:Endotoxins; D016166:Free Radical Scavengers; D005609:Free Radicals; D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; D008315:Malondialdehyde; D000242:Cyclic AMP; D010431:Pentoxifylline