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 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.
Hatherill
J R
JR
Department of Medicine, Stanford University Medical Center, CA 94305-5236.
Yonemaru
M
M
Zheng
H
H
Hoffmann
H
H
Fujishima
S
S
Ishizaka
A
A
Raffin
T A
TA
D000208:Acute Disease; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004912:Erythrocytes / Q000378:metabolism; D004927:Escherichia coli Infections / Q000188:drug therapy; D006168:Guinea Pigs; D007275:Injections, Intravenous; D007457:Iodine Radioisotopes; D007958:Leukocyte Count; D008171:Lung Diseases / Q000139:chemically induced / Q000188:drug therapy*; D010431:Pentoxifylline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D012141:Respiratory Tract Infections / Q000188:drug therapy*; D013805:Theobromine / Q000031:analogs & derivatives*
D001993:Bronchodilator Agents; D007457:Iodine Radioisotopes; C062028:1-(5-hydroxy-5-methylhexyl)-3-methylxanthine; D013805:Theobromine; D010431:Pentoxifylline