Ethyl Pyruvate Provides Therapeutic Benefits to Resuscitation Fluids

摘要

Many promising strategies in experimental models of hemorrhage have failed in clinical trials, in part because classical experimental models may not mimic clinical settings. Unlike classical experimental models, hemorrhage in critical care is normally associated with collateral trauma that affects the physiological responses during resuscitation. Unlike rodents, swine are an optimal species donor for experimental hemorrhage as they have an anatomy, physiology and hemodynamic responses that closely resembles human. Here, we analyze whether ethyl pyruvate can provide a therapeutic anti-inflammatory value to resuscitation fluids in porcine hemorrhage with trauma. Ethyl pyruvate prevented systemic TNF levels, hyperglycemia, aspartate aminotransferase and preserved the intrinsic coagulation pathway. Resuscitation with ethyl pyruvate attenuated TNF levels in the spleen, liver and intestine. The most significant effects were found in the terminal ileum were ethyl pyruvate inhibited TNF levels, restrained myelopyroxidase activity, preserved the intestinal epithelium, and prevented the appearance of bacterial endotoxin in the serum. Unlike observed in rodents, ethyl pyruvate did not attenuate TNF levels in the lung and the heart, providing a potential explanation for its failure in clinical trials of cardiopulmonary bypass. These results suggest that ethyl pyruvate provided significant effects in porcine hemorrhage previously undetected in rodents. These results suggest that anti-inflammatory adjuvant in resuscitation fluids can prevent organ damage and it may decrease the susceptibility to secondary sepsis during resuscitation.