Evidence for Early Bacteremia/Endotoxemia and Inflammatory Responses after Trauma – Hemorrhage and Complement Activation in a Nonhuman Primate Model

Abstract

There is criticism that the major line of evidence regarding posttraumatic inflammatory response and bacterial translocation has mainly come from experiments in rodents. The aim of this study was therefore to investigate the very early bacteremia/endotoxemia and inflammatory response in nonhuman primates.Six baboons were subjected to hemorrhagic shock (40 mm Hg mean arterial pressure) preceded by infusion of zymosan-activated plasma (to simulate trauma-associated complement activation) followed by reinfusion for 1 h. Measurements of complement and granulocyte (PMN) activation, cytokines of the inflammatory network, soluble cytokine receptors, and bacteria/endotoxin translocation (BT) were performed.There were significantly increased levels of PMN elastase, interleukin-6, and soluble tumor necrosis factor (TNF) receptors, but not of TNF. BT was evident from positive blood cultures, and from trendwise increased endotoxin plasma levels. Early liver damage was shown from elevated glutathione S-transferase (GST) plasma levels.Complement activation and hemorrhagic shock lead to an early inflammatory response together with bacteremia/endotoxemia as evidence of translocation from the gut already during the shock period in subhuman primates.

Immunoglobulin Enriched Colostral Milk Reduces Gut-Derived Endotoxemia in a Rat Hemorrhage Model

“…In line with previous experiments [3,12,13] hemorrhagic shock in the present study resulted in an increase in endotoxin concentrations in the systemic circulation. It could be argued that the amount of LPS found in plasma may be too low to result in significant pathological alterations.…”

“…From both experimental and clinical data, there is increasing evidence suggesting that one of the initiating events in the sepsis syndrome following hypovolemic insults might be the entry of bacteria and endotoxin (lipopolysaccharide, LPS) into the blood of traumatized, hypotensive patients [2][3][4][5][6]. The pathophysiologic relevance of gut-derived bacteremia/endotoxemia after shock remains, however, controversial [7][8][9].…”

Metabolic changes after polytrauma: an imperative for early nutritional support

“…Severe trauma induces massive changes of the physiological state by alteration of metabolic pathways and activation of the innate immune system [ 1 - 5 ]. The posttraumatic metabolic changes are characterized by hypermetabolism with increased energy expenditure, enhanced protein catabolism, insulin resistance associated with hyperglycemia, failure to tolerate glucose load, and high plasma insulin levels ("traumatic diabetes") [ 1 , 2 , 6 - 11 ].…”

Large Animal Models: Baboons for Trauma, Shock, and Sepsis Studies

“…Elevated plasma lipopolysaccharide (LPS) levels were found in HTS baboons at the end of a 3-h shock period and 1 h after the beginning of reinfusion. Similarly, in a subchronic model in baboons consisting of oxygen debt-controlled hemorrhage together with an infusion of zymosan-activated plasma (with activated complement components), the highest plasma endotoxin levels were detected at the end of the 3-to 4-h shock period and at 1 h after the start of reinfusion (15,21). The results obtained in subhuman primate models are in agreement with reports of bacterial translocation, mainly in rodents (22)(23)(24)(25)(26), and provide further evidence that the phenomenon of translocation may not be limited to lower animals.…”

“…Such models were set up in primates (14) where bone fracture and soft tissue injury was induced in anesthetized animals (with euthanasia after finishing the acute part of the experiment) or complement activation (by infusion of zymosan-activated plasma [15] or cobra venom factor [16]) was accomplished in subchronic studies as one of the most important components of trauma (17). Such models were used and previously reported in this journal (18,19).…”