Early post-treatment with pentoxifylline or dibutyryl cAMP attenuates Escherichia coli-induced acute lung injury in guinea pigs.
We examined effects of early post-treatment with the methylxanthine pentoxifylline (PTXF), or the cell-permeable adenosine 3', 5'-cyclic monophosphate (cAMP) analog dibutyryl cAMP (db-cAMP) on Escherichia-coli-induced acute lung injury in guinea pigs. Acute lung injury was assessed by measurements of lung water (lung wet/dry weight ratio; W/D ratio), the concentration ratio of 125I-albumin in bronchoalveolar lavage (BAL) fluid and lung tissue compared with plasma (albumin index; BAL-AI or tissue-AI), and total differential leukocyte count in BAL fluid. Mean arterial pressure (Pa) and peripheral WBC counts were monitored continuously over the 8-h experiment. Septicemia was induced by a bolus injection of 2 x 10(9)/kg live E. coli. Thirty minutes later the animals received a bolus injection followed by continuous infusion of PTXF (20 mg/kg + 20 mg/kg/h; n = 8) or db-cAMP (2 mg/kg + 2 mg/kg/h; n = 8) or saline (septic control; n = 8). Nonseptic control groups were also studied. The lung W/D ratio, BAL-AI, lung tissue-AI, and BAL leukocyte count increased significantly in the septic control group. The PTXF-septic and db-cAMP-septic groups showed no significant increase in lung W/D ratio, BAL-AI, and lung tissue-AI. However, there was no difference in BAL total and differential leukocyte count as compared with the septic control group. PTXF and db-cAMP had no effect on E. coli-induced changes in peripheral WBC count and Pa. Comparison in vitro experiments demonstrated that PTXF and db-cAMP inhibited the endotoxin-induced (E. coli) chemiluminescent response of isolated guinea-pig polymorphonuclear leukocytes (PMN).(ABSTRACT TRUNCATED AT 250 WORDS)
Hoffmann
H
H
Department of Medicine, Stanford University Medical Center, CA.
Hatherill
J R
JR
Crowley
J
J
Harada
H
H
Yonemaru
M
M
Zheng
H
H
Ishizaka
A
A
Raffin
T A
TA
D000818:Animals; D001794:Blood Pressure; D001992:Bronchoalveolar Lavage Fluid / Q000378:metabolism; D003994:Bucladesine / Q000008:administration & dosage* / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000150:complications*; D006168:Guinea Pigs; D007958:Leukocyte Count / Q000187:drug effects; D008163:Luminescent Measurements; D008171:Lung Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D009929:Organ Size; D010431:Pentoxifylline / Q000008:administration & dosage* / Q000494:pharmacology; D011654:Pulmonary Edema / Q000473:pathology; D012709:Serum Albumin / Q000378:metabolism
D004731:Endotoxins; D012709:Serum Albumin; D003994:Bucladesine; D010431:Pentoxifylline