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
myeloperoxidase in the major organs.
Resuscitation with
ethyl pyruvate provided an anti-inflammatory potential to restrain serum TNF and high-mobility group B
protein 1 levels.
Ethyl pyruvate inhibited
nuclear factor [kappa]B in the spleen but not in the other major organs. In contrast,
ethyl pyruvate inhibited NO 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
myeloperoxidase activity, preserved the intestinal epithelium, and prevented the systemic distribution of bacterial
endotoxin.
Ethyl pyruvate can provide therapeutic anti-inflammatory benefits to modulate splenic
nuclear factor [kappa]B, restrain inflammatory responses, and prevent
hyperglycemia, the intrinsic coagulation pathway, and organ injury in porcine
hemorrhage without
trauma.