Abstract |
The protective effect of xanthines against E. coli-induced and cytokine-induced lung injury in guinea-pigs has been demonstrated recently. In the present study, the possible protective effects were examined of an analogue of pentoxifylline, HWA-138, a xanthine derivative, on lung injury in septic guinea-pigs. Three groups of animals were studied over a period of 8 hours: Group I animals--saline control injected intravenously with 3 ml 2% lysine/ normal saline followed by a continuous lysine/saline infusion (1 ml/kg/hr); Group II--septic control injected intravenously with 2 x 10(9)/kg Escherichia coli followed by a continuous lysine/saline infusion (1 ml/kg/hr); and Group III--E. coli septicaemia plus HWA-138 continuous infusion ( HWA-138 dissolved in lysine/saline) began with a bolus (10 mg/kg) followed by a HWA-138 continuous infusion (3 mg/kg/hr) started 60 minutes before injection of E. coli. Arterial blood pressure and white blood cell counts were monitored serially for 8 hours. Lung water (wet-to-dry ratio) and the concentration ratio of 125I-labelled albumin in bronchoalveolar lavage (BAL) fluid and lung tissue compared to plasma (125I- albumin BAL/plasma, 125I- albumin lung/plasma) were examined. Results demonstrated that an intravenous injection of E. coli caused an increased W/D ratio (p less than 0.01) and an increased 125I-albumin lung/plasma ratio (p less than 0.01). In contrast, the HWA-138-treated group did not demonstrate significantly increased W/D lung ratios (p less than 0.01) and 125I-albumin lung/plasma ratios (p less than 0.05). The data suggest a possible role for HWA-138 in attenuating sepsis-induced lung injury.
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Authors | J R Hatherill, M Yonemaru, H Zheng, H Hoffmann, S Fujishima, A Ishizaka, T A Raffin |
Journal | Pharmatherapeutica
(Pharmatherapeutica)
Vol. 5
Issue 6
Pg. 407-15
( 1989)
ISSN: 0308-051X [Print] England |
PMID | 2687896
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Bronchodilator Agents
- Iodine Radioisotopes
- 1-(5-hydroxy-5-methylhexyl)-3-methylxanthine
- Theobromine
- Pentoxifylline
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Topics |
- Acute Disease
- Animals
- Blood Pressure
(drug effects)
- Bronchodilator Agents
(administration & dosage, therapeutic use)
- Erythrocytes
(metabolism)
- Escherichia coli Infections
(drug therapy)
- Guinea Pigs
- Injections, Intravenous
- Iodine Radioisotopes
- Leukocyte Count
- Lung Diseases
(chemically induced, drug therapy)
- Pentoxifylline
(administration & dosage, analogs & derivatives, therapeutic use)
- Respiratory Tract Infections
(drug therapy)
- Theobromine
(analogs & derivatives)
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