EFFICACY OF HEPARIN AND ANTITHROMBIN-III IN FLUID-RESUSCITATED CECAL LIGATION AND PUNCTURE

Sepsis/septic shock and multiple organ failure are important causes of morbidity and mortality. Our objective was to study sepsis and organ failure in a fluid-resuscitated septic model. Male S-D rats were anest hetized with halothane, the jugular vein catheterized, and CLP perform ed. Each rat was maintained in a metabolism cage on continuous intrave nous fluid (3 mL/h/rat). Urine rate and [creatinine](urine) were measu red daily. At day 5, serum creatinine with chemistry profile, complete blood count, clotting times, and wet lung/body weight ratios were als o measured. Glomerular filtration rate (GFR) was measured according to the principle of endogenous creatinine clearance. GFR was correlated with the product of urine rate x [creatinine](urine) (R = .79), so tha t product was used as a daily indicator of GFR. Urine output remained greater than or equal to normal during sepsis. Heparin and antithrombi n III were tested in this model. The model was associated with 40% mor tality, a 60% reduction in platelet count, liver damage, a 75% reducti on in renal function, muscle damage, and a normal wet lung/body weight ratio. Treatment with heparin/antithrombin III ameliorated the decrea se in GFR (p <.05) observed in the nontreated animals, prevented the s eptic-induced thrombocytopenia (p <.05), and improved survival (p = .0 5).