Hemorrhage‐induced Hyperglycemia Improved with Acute TNFα blockade in the Obese Zucker Rat

Abstract

Post‐hemorrhage hyperglycemia is correlated with increased inflammation and mortality. Obese patients show exacerbated inflammation and complications to severe blood loss. However, whether hemorrhage leads to exaggerated inflammation‐mediated hyperglycemia in obesity has not been examined. We hypothesized that obese Zucker rats (OZ) have exaggerated hyperglycemic responses to hemorrhage and that acutely blocking TNFα will improve glucose responses. Fasted lean Zucker rats (LZ) and OZ were treated with a TNFα antagonist, etanercept (2mg/kg, sq.), (LZE and OZE, respectively), or saline (0.2 ml) 3 hours before hemorrhage. Hemorrhage was induced by withdrawing blood (35% total volume) over 10 minutes. Plasma glucose levels and blood pressure were measured during a 3 hour recovery period. There were no differences among groups in basal glucose levels or blood pressure before and immediately after hemorrhage. However, average glucose levels during the 3 hours after hemorrhage were higher in OZ (459 ± 40 mg/dl) but not OZE (315 ± 18 mg/dl) as compared to LZ (263 ± 24 mg/dl) and LZE (315 ± 42 mg/dl). We conclude that after hemorrhage, OZ exhibits an increased TNFα–mediated hyperglycemia, which could be responsible for the increased vulnerability to hemorrhagic shock seen in obese patients. Supported by NIH HL‐51971, HL‐89581, T32 HL‐105324, AHA‐12SDG12050525