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

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 10⁹/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 < 0.01) and an increased ¹²⁵I-albumin lung/plasma ratio (p < 0.01). In contrast, the HWA-138-treated group did not demonstrate significantly increased W/D lung ratios (p < 0.01) and ¹²⁵I-albumin lung/plasma ratios (p < 0.05). The data suggest a possible role for HWA-138 in attenuating sepsis-induced lung injury.