Attenuation of acute lung injury in septic guinea-pigs by a new xanthine derivative (HWA-138).

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.

• 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)

Chemical References

• Bronchodilator Agents
• Iodine Radioisotopes
• 1-(5-hydroxy-5-methylhexyl)-3-methylxanthine
• Theobromine
• Pentoxifylline

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)