Attenuation of acute lung injury in septic guinea pigs by pentoxifylline.
Pentoxifylline (PTXF), a drug demonstrated to improve intermittent claudication, is a methylxanthine that increases intracellular cyclic AMP (cAMP) and, unlike theophylline, has few side effects. Because increased cAMP levels have been associated with a decrease in lung injury, we examined the effects of PTXF on acute lung injury in a septic guinea pig model. Five groups of guinea pigs were studied over a period of 8 h. (Group I: saline control injected intravenously with 2 ml of saline; Group II: septic control injected intravenously with 2 x 10(9) Escherichia coli; Group III: E. coli septicemia plus PTXF bolus 20 mg/kg injected 5 min before E. coli injection; Group IV: E. coli septicemia plus PTXF continuous infusion, begun with bolus [20 mg/kg] followed by continuous infusion [20 mg/kg/h] started 60 min before injection of E. coli; Group V: PTXF continuous infusion [20 mg/kg/h] control). Arterial blood gases, arterial blood pressure, and blood WBC counts were monitored serially for 8 h. Lung water (wet-to-dry ratio), the concentration ratio of 125I-labeled albumin in bronchoalveolar lavage (BAL) fluid to that in plasma (albumin index; AI), total cell count in BAL fluid, thiobarbituric-acid-reactive material (TBARM), and the lysosomal enzyme beta-glucuronidase (beta-G) were examined. Lung tissue was studied histologically to assess neutrophil accumulation. Our results showed that E. coli septicemia caused significant peripheral neutropenia and histopathologic evidence of neutrophil alveolitis associated with an increased ratio of TBARM and beta-G in BAL fluid as compared with those in plasma (TBARM BAL ratio and beta-G BAL ratio).(ABSTRACT TRUNCATED AT 250 WORDS)
Ishizaka
A
A
Department of Medicine, Stanford University Medical Center, CA 94305-5236.
Wu
Z H
ZH
Stephens
K E
KE
Harada
H
H
Hogue
R S
RS
O'Hanley
P T
PT
Raffin
T A
TA
D000208:Acute Disease; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000032:analysis / Q000166:cytology; D004927:Escherichia coli Infections / Q000150:complications; D005260:Female; D005966:Glucuronidase / Q000378:metabolism; D006168:Guinea Pigs; D008168:Lung / Q000473:pathology; D008171:Lung Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009504:Neutrophils / Q000473:pathology; D010431:Pentoxifylline / Q000627:therapeutic use*; D018805:Sepsis / Q000150:complications*; D013805:Theobromine / Q000031:analogs & derivatives*; D013858:Thiobarbiturates / Q000494:pharmacology
D013858:Thiobarbiturates; D005966:Glucuronidase; C029684:thiobarbituric acid; D013805:Theobromine; D010431:Pentoxifylline