Abstract |
We have evaluated the potential therapeutic effects of the xanthine derivatives HWA 138 (1-(5 hydroxy-5-methylhexyl)-3-methylxanthine) and A 80,2715 (1-(5 hydroxy-5-methylhexyl)-3-methyl-7-propylxanthine) on acute lung injury in endotoxemic pigs when administered following the septic insult. Salmonella abortus equi endotoxin (LPS) was given as a continuous intravenous infusion of 2 micrograms/kg/h over a period of 8 h. 1 h after the start of the LPS infusion the animals received a bolus injection followed by continuous infusion of A 80,2715 (3 mg/kg + 1.5 mg/kg/h; n = 6), HWA 138 (3 mg/kg + 1.5 mg/kg/h; n = 6), or saline (LPS control; n = 6). Treatment with A 80,2715 or HWA 138 inhibited the LPS-induced increases in the pulmonary artery pressure (p < .05; ANOVA) and in lung wet/dry weight ratio (p < .05), and ameliorated the LPS-induced deterioration in lung mechanics (decreased lung dynamic compliance (p < .05); increased peak airway pressure (p < .05)). Xanthine treatment, however, failed to significantly improve arterial PO2 and did not affect peripheral leukopenia. The results of this study suggest a potential therapeutic role for HWA 138 and A 80,2715 in attenuating endotoxin-induced acute lung injury.
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Authors | H Hoffmann, M Weis, G Frank, A Birg, M M Schönharting, M Jochum |
Journal | Shock (Augusta, Ga.)
(Shock)
Vol. 4
Issue 3
Pg. 166-70
(Sep 1995)
ISSN: 1073-2322 [Print] United States |
PMID | 8574750
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Bronchodilator Agents
- Lipopolysaccharides
- Xanthines
- 1-(5-hydroxy-5-methylhexyl)-3-methylxanthine
- A 802715
- Pentoxifylline
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Topics |
- Animals
- Bronchodilator Agents
(therapeutic use)
- Hemodynamics
- Infusions, Intravenous
- Leukocyte Count
- Leukopenia
(complications, pathology)
- Lipopolysaccharides
- Pentoxifylline
(analogs & derivatives, therapeutic use)
- Pulmonary Circulation
(drug effects)
- Respiratory Distress Syndrome
(drug therapy, etiology, physiopathology)
- Shock, Septic
(complications, drug therapy, physiopathology)
- Swine
- Swine, Miniature
- Xanthines
(therapeutic use)
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