Effects of hyperglycemia and insulin therapy on outcome in a hyperglycemic septic model of critical illness.

Background: The effects of hyperglycemia and insulin therapy on septic outcome have not been well studied.

Methods: Septic hyperglycemia was induced by infusion of TPN (254 kcal/kg x d) immediately following cecal ligation and puncture (CLP) surgery in rats. Animals (N = 109) were monitored for blood glucose and followed for survival for 4 days.

FoxA2 involvement in suppression of protein C, an outcome predictor in experimental sepsis.

Low levels of protein C (PC) predict outcome as early as 10 h after insult in a rat polymicrobial sepsis model and were associated with suppression of PC mRNA, upstream transcription factor FoxA2, and cofactor hepatocyte nuclear factor 6 (HNF6). Small interfering RNA suppression of FoxA2 in isolated hepatocytes demonstrated regulation of both its cofactor HNF6 and PC. Our data suggest that reduced FoxA2 may be important in the suppression of PC and resulting poor outcome in sepsis.

Cecal ligation and puncture with total parenteral nutrition: a clinically relevant model of the metabolic, hormonal, and inflammatory dysfunction associated with critical illness.

Background: Standard rat cecal ligation and puncture (CLP) results in only transient hyperglycemia, making an examination of the effects of glucoregulatory agents, such as insulin, on the morbidity and mortality of CLP problematic. Accordingly, we sought to develop a model of rat CLP with prolonged hyperglycemia through continuous infusion of total parenteral nutrition (TPN) post CLP.

Materials And Methods: Polyethylene catheters were implanted into the femoral vein of female Sprague Dawley rats (245-265 g) which were subsequently subjected to CLP.

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

Objective: To evaluate protein C and other factors associated with the septic response as predictors of mortality in a clinically relevant animal model of sepsis.

Design: Laboratory investigation.

Setting: Eli Lilly and Company discovery research laboratory.