Modulators of plasma fibronectin response during sepsis.
Plasma fibronectin (PFN) depletion has been associated with poor outcome in patients with sepsis or those who have experienced trauma; restoration of normal levels appears beneficial. PFN synthesis is increased after cecal ligation even in malnourished animals with sepsis, implying that stimulation of endogenous PFN synthesis is possible. One hundred rats received either a single therapeutic agent (gelatin, heparin, indomethacin, urokinase, captopril, or endotoxin) or the combination of a cecal ligation and a single agent (cimetidine, methylprednisolone, epsilon-aminocaproic acid (EACA), or transaminomethyl cyclohexane carboxylic acid. PFN levels were measured by enzyme-linked immunosorbent assay at 0, 24, and 48 hours. Only endotoxin alone caused significant PFN elevation at 24 to 48 hours (p less than 0.01); however, its multiplicity of effects precludes localization of regulatory pathways. Methylprednisolone results in an accelerated rise in PFN levels after operation (p less than 0.05), probably through an intracellular augmentation PFN synthesis. EACA attenuates the postoperative response while transaminomethyl cyclohexane carboxylic acid augments the PFN rise. This effect of EACA implies the existence of a proteolytic fragment capable of stimulating PFN synthesis. If a nontoxic factor can be identified, the use of exogenous PFN may be avoided.
D015119:Aminocaproic Acid / Q000494:pharmacology; D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D002432:Cecum / Q000601:surgery; D004731:Endotoxins / Q000494:pharmacology; D004926:Escherichia coli; D005353:Fibronectins / Q000097:blood*; D007239:Infections / Q000097:blood*; D007249:Inflammation / Q000097:blood*; D008026:Ligation; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014148:Tranexamic Acid / Q000494:pharmacology
D004731:Endotoxins; D005353:Fibronectins; D011480:Protease Inhibitors; D014148:Tranexamic Acid; D015119:Aminocaproic Acid; D008775:Methylprednisolone