ARDS-like lung injury produced by endotoxin in platelet-activating factor-primed rats.
We recently reported that the combined administration of lipopolysaccharide (LPS) and platelet-activating factor (PAF) in rats, at doses that are completely devoid of any effect when given alone, caused lung injury characterized by neutrophil adhesion to lung capillaries and postcapillary venules, neutrophil accumulation in the lung parenchyma, platelet-fibrin deposits in postcapillary venules, and pulmonary edema. A marked increase in lung myeloperoxidase activity and an elevation of serum tumor necrosis factor-alpha and thromboxane B2, along with leukopenia and thrombocytopenia, were also noticed. The present study aimed to examine whether repeated LPS-PAF stimulus can cause progressive lung injury reminiscent of adult respiratory distress syndrome (ARDS). A second LPS-PAF challenge, 4 h (n = 11) after the original challenge, induced mortality (69% at 24 h, P < 0.01) and some of the pathological changes seen in clinical ARDS, including severe pulmonary edema, alveolar proteinaceous exudates, monocytic infiltration, and a further increase in lung myeloperoxidase activity (700%, P < 0.01). Repeated LPS-PAF dosing also resulted in sustained increased serum tumor necrosis factor-alpha levels (1,610 +/- 470 pg/ml, P < 0.01) and further exacerbation of the leukopenia (-68 +/- 6%, P < 0.01) and thrombocytopenia (-65 +/- 8%, P < 0.01). These data suggest that repeated LPS-PAF actions are sufficient to elicit pathophysiology of ARDS-like lung injury.
Department of Surgery, Jefferson Medical College, Philadelphia 19107.
R
R
Rabinovici
P J
PJ
Bugelski
K M
KM
Esser
L M
LM
Hillegass
J
J
Vernick
G
G
Feuerstein
D000818:Animals; D004195:Disease Models, Animal; D004731:Endotoxins / Q000008:administration & dosage / Q000633:toxicity*; D006439:Hemodynamics; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity; D008168:Lung / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury; D008297:Male; D008854:Microscopy, Electron; D010972:Platelet Activating Factor / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D013929:Thromboxane B2 / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004731:Endotoxins; D008070:Lipopolysaccharides; D010972:Platelet Activating Factor; D014409:Tumor Necrosis Factor-alpha; D013929:Thromboxane B2