The 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. Males S-D rats were anesthetized with halothane, the jugular vein catheterized, and CLP performed. Each rat was maintained in a metabolism cage on continuous intravenous fluid (3 mL/rat). Urine rate and [creatinine]urine were measured daily. At day 5, serum creatinine with chemistry profile, complete blood count, clotting times, and wet lung/body weight ratios were also 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 that product was used as a daily indicator of GFR. Urine output remained > or = normal during sepsis. Heparin and antithrombin III were tested in this model. The model was associated with 40% mortality, a 60% reduction in platelet count, liver damage, a 75% reduction in renal function, muscle damage, and a normal wet lung/body weight ratio. Treatment with heparin/antithrombin III ameliorated the decrease in GFR (p < .05) observed in the nontreated animals, prevented the septic-induced thrombocytopenia (p < .05), and improved survival (p = .05).
Yang
S
S
Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing 48824, USA.
Hauptman
J G
JG
D000818:Animals; D000990:Antithrombin III / Q000627:therapeutic use*; D002432:Cecum / Q000293:injuries*; D004195:Disease Models, Animal; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006493:Heparin / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008026:Ligation; D008297:Male; D009102:Multiple Organ Failure / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D010538:Peritonitis / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation; D018805:Sepsis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D013921:Thrombocytopenia / Q000517:prevention & control; D014950:Wounds, Penetrating
D000990:Antithrombin III; D006493:Heparin