Evaluation of protein C and other biomarkers as predictors of mortality in a rat cecal ligation and puncture model of sepsis

Critical Care Medicine
Josef G HeuerJoseph A Jakubowski

Abstract

To evaluate protein C and other factors associated with the septic response as predictors of mortality in a clinically relevant animal model of sepsis. Laboratory investigation. Eli Lilly and Company discovery research laboratory. Forty female Sprague Dawley rats weighing 245-265 g. Polyethylene catheters were surgically implanted into the femoral vein and sepsis was induced by cecal ligation and puncture (CLP). A solution of 5% dextrose in 0.9 % saline was continuously infused via femoral catheters immediately following surgery. Blood sampling was done before surgery and at 6 and 20 hrs after surgery. Rats were then monitored for survival out to 4 days. Blood collections were used to measure blood glucose, bacteremia, plasma protein C, D-dimer, hormones, chemokines, cytokines, and myoglobin (as a marker of organ damage). Mortality was categorized into three groups: early death (before 30 hrs post-CLP), late death (after 30 hrs post-CLP), and survivors (96 hrs post-CLP). Compared with survivors, early death rats had statistically significant differences in 30 variables indicative of severe inflammation, coagulopathy, and muscle damage including less bacterial clearance, hypoglycemia, lower plasma protein C, higher plasma D dime...Continue Reading

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