Survival and Inflammatory Responses in Experimental Models of Hemorrhage

Abstract

Alternative experimental models of hemorrhage mimic particular conditions of clinical settings and provide advantages to analyze novel resuscitation treatments. Here, we compared alternative models of hemorrhage and analyzed the effects of resuscitation with Hextend. Adult male Sprague-Dawley rats underwent alternative models of hemorrhage: anesthetized without trauma, anesthetized with trauma, or conscious (unanesthetized) hemorrhage. Each model of hemorrhage includes three experimental groups: (C) control without hemorrhage or resuscitation treatment; (NR) animals with hemorrhage but without resuscitation; and (HX) animals with hemorrhage and resuscitation treatment with Hextend. Conscious animals required the highest hemorrhagic volume, whereas hemorrhage with trauma required the lowest blood volume withdrawal to achieve the same arterial pressure. Conscious hemorrhage exhibited the fastest mortality, but anesthetized animals with or without trauma had similar mortality kinetic. These survival rates did not correlate with blood chemistry, hemodynamic responses, or serum TNF and HMGB1 levels. Hemorrhage in conscious animals or anesthetized animals with trauma increased serum TNF levels by approximately 2-fold compared with hemorrhage in anesthetized animals without trauma. Animals in conscious hemorrhage had similar TNF increases in all the organs, but trauma induced a specific TNF overproduction in the spleen. Resuscitation with Hextend improved survival in all the experimental models, yet its survival benefits were statistically greater in anesthetized animals with trauma. The only two markers similar to the survival benefits of Hextend were the TNF levels in the lung and liver. Hextend significantly improved survival and inhibited pulmonary and hepatic TNF levels in all the experimental models. The survival benefits of resuscitation with Hextend depended on the experimental models and did not correlate with blood chemistry, hemodynamic, or serum cytokine levels. However, resuscitation with Hextend inhibited TNF levels in the lung and the liver with a pattern that resembled the survival benefits.