Ethyl Pyruvate Prevents Inflammatory Responses and Organ Damage During Resuscitation in Porcine Hemorrhage

Abstract

Hemorrhage remains a common cause of death despite the recent advances in critical care, in part because conventional resuscitation fluids fail to prevent lethal inflammatory responses. Here, we analyzed whether ethyl pyruvate can provide a therapeutic anti-inflammatory potential to resuscitation fluids and prevent organ damage in porcine hemorrhage. Adult male Yorkshire swine underwent lethal hemorrhage with trauma and received no resuscitation treatment or resuscitation with Hextend alone, or supplemented with ethyl pyruvate. Resuscitation with ethyl pyruvate did not improve early hemodynamics, but prevented hyperglycemia, the intrinsic coagulation pathway, serum aspartate aminotransferase, and myelopyroxidase in the major organs. Resuscitation with ethyl pyruvate provided an anti-inflammatory potential to restrain serum TNF and HMGB1 levels. Ethyl pyruvate inhibited NF-kB in the spleen but not in the other major organs. In contrast, ethyl pyruvate inhibited nitric oxide in all the major organs and it also inhibited TNF production in the major organs but in the lung and heart. The most significant effects were found in the terminal ileum where ethyl pyruvate inhibited cytokine production, restrained myelopyroxidase activity, preserved the intestinal epithelium, and prevented the systemic distribution of bacterial endotoxin. Ethyl pyruvate can provide therapeutic anti-inflammatory benefits to modulate splenic NF-kB, restrain inflammatory responses, and prevent hyperglycemia, the intrinsic coagulation pathway and organ injury in porcine hemorrhage without trauma.

Ethyl pyruvate diminishes the inflammatory response to lipopolysaccharide infusion in horses

“…Ethyl pyruvate also prevented bacterial translocation and maintained intestinal barrier function following thermal injury in rats [13]. In a swine haemorrhagic shock model, EP blocked cytokine production, suppressed myelopyroxidase activity, and preserved the epithelium of the terminal ileum, preventing the systemic distribution of bacterial endotoxins [14].…”

Preliminary safety and biological efficacy studies of ethyl pyruvate in normal mature horses

“…Interestingly, in a porcine haemorrhagic shock model, ethyl pyruvate in Hextend did not improve haemodynamics compared to Hextend alone (Dong et al . 2009); however, resuscitation with ethyl pyruvate preserved intestinal morphology, maintained serum bacterial endotoxin levels similar to those of controls and prevented up regulation of the intrinsic coagulation pathway (Dong et al . 2009).…”

Reperfusion strategies in the management of extremity vascular injury with ischaemia

“…A recent study from Crawford et al 11 reported that in a murine model of limb ischaemia ethyl pyruvate pretreatment resulted in a lower percentage of injured muscle fibres. It also decreased inflammatory markers and reduced tissue thrombosis65. Ethyl pyruvate is a promising medication that appears to modulate the effects of ischaemia–reperfusion injury.…”

“…Dong and co‐workers65 recently reported that, in a swine model of shock, inclusion of ethyl pyruvate during resuscitation resulted in decreased circulating markers of inflammation and less organ damage. A recent study from Crawford et al 11 reported that in a murine model of limb ischaemia ethyl pyruvate pretreatment resulted in a lower percentage of injured muscle fibres.…”