Ethyl pyruvate improves systemic and hepatosplanchnic hemodynamics and prevents lipid peroxidation in a porcine model of resuscitated hyperdynamic endotoxemia*

Abstract

Ethyl pyruvate infusion resulted in improved hemodynamic stability and ameliorated acid-base derangements induced by chronic endotoxemia in pigs. Reduced oxidative stress and an decreased nitric oxide release probably contributed to these effects.

Ethyl pyruvate protects against experimental acute-on-chronic liver failure in rats

“…EP has been shown to be beneficial in a variety of animal models of acute and chronic inflammatory conditions [21][22][23][24][25][26][27][28]47,48] . This study investigated whether EP had protective effects on the ACLF model.…”

“…Therefore, we proposed that HMGB1 as an important inflammatory mediator of endotoxemia should also play a significant role in the pathogenesis of liver failure [20] . Ethyl pyruvate (EP), a simple aliphatic ester derived from pyruvic acid, has been shown to improve survival and ameliorate organ dysfunction in a variety of animal models of critical illness, including acute endotoxemia [21] , polymicrobial bacterial sepsis [22] , postsurgical ileus [23] , burn injury [24] , acute pancreatitis [25] , organ ischemia and reperfusion injury [26,27] , and hemorrhagic shock [28] . As an effective anti-inflammatory agent, EP inhibits the activation of key inflammatory signaling pathways [29,30] , and down-regulates the secretion of multiple inflammatory proteins, including IL-6, TNF-α and HMGB1 [31][32][33] .…”

Efficacy of an Extracorporeal Endotoxin Adsorber System during Hyperdynamic Porcine Endotoxemia

“…It must be emphasized that patients with sepsis present with considerable inhomogeneity, due to different etiology, variable microbiology findings and unknown onset of the disease, which impedes stratification. To avoid those difficulties, we therefore tested the efficacy of endotoxin adsorption during resuscitated, hyperdynamic endotoxemia by continuous intravenous endotoxin infusion [18,19] . We investigated both 'early' endotoxin adsorption, i.e.…”

“…The rate of endotoxin infusion was then reduced to 0.4 g/kg/h, and this infusion rate was maintained until the end of the experiment in all groups. The infusion rate was selected according to previous experience with long-term continuous intravenous endotoxin infusion in pigs that could be sustained over 24 h [18][19][20][21] .…”

“…Twenty domestic pigs (Deutsches Landschwein) of either sex with a median body weight of 52 kg (range 45-60) were fasted for 24 h, with water ad libitum. The surgical preparation as well as physiologic measurements and calculations were performed as recently described in detail [18][19][20][21] .…”