Coagulation and sepsis in murine models
OA Version
Citation
Abstract
Sepsis is a widespread and expensive health issue that annually affects millions of individuals in the United States. Despite significant research investments, there has yet to be a single proven effective therapy, resulting in the sustained high mortality and morbidity counts. Sepsis is a multifaceted and complex problem, affecting many systems in the body. Thus, steady investigations have been made to determine the mechanisms of the pathophysiology and multi-level systems involved in septic immune response.
The purpose of this study aims to determine if sepsis affects coagulation. The secondary aim seeks to reproduce findings on the effects of hydrocortisone, ascorbic acid, and thiamine triple therapy on septic mortality. This was achieved through the induction of peritonitis through cecal ligation and puncture (CLP) in murine models. Prothrombin time (PT), as well as plasma glypican (GPC) levels, were measured and analyzed in mice stratified by different septic phenotype categories. Furthermore, the non-invasive physiologic parameters were evaluated to see if there were substantive evidence of changes or other body systems being affected by sepsis and treatment method.
Results showed that there were significant differences in weight, temperature, heart rate, respiratory rate, and oxygen saturation post-CLP, in which mice predicted to die (P-Die) had lower values than mice predicted to live (P-Live). In most cases, the significant differences within P-Live and P-Die mice occurred within 6hrs post-CLP. This suggests that effective therapy includes early intervention. The PT levels revealed there was a significant difference between VEH/P-Live (M=15.58, SD=5.8) and VEH/P-Die (M=24.03, SD=133), p=0.0428. This demonstrated that P-Die mice had elevated prothrombin times as anticipated.
The findings also found that GPC-1 levels were significantly elevated in mice predicted to die in both HAT-treated and vehicle groups; HAT/P-Die (M=3658, SD=3516), VEH/P-Die (M=8845, SD=1966), p=0.0143. This hinted at the possibility of HAT improving glycocalyx shedding. It also found that GPC-1 levels were significantly higher in VEH/P-Die (M=8845, SD=1966) when compared to VEH/P-Live (M=1516, SD=1485), p<0.0001. Results for GPC-4 were found to be correlated to GPC-1 levels, r(40)=.74. Thus, it was observed GPC-4 levels were also significantly elevated in mice predicted to die in both Hat-treated and vehicle groups; HAT/P-Die (M=2182, SD=1267) and VEH/P-Die (M=4515, SD=667.3), p=0.0038. And finally, GPC-4 levels were elevated in VEH/P-Die mice (M=4515, SD=667.3) compared to in VEH/P-Live mice (M=2033, SD=480.3), p<0.0001.
Therefore, the study found that P-Die Mice have increased PT and elevated GPC levels. This can be seen in association between the activation of coagulation leading to consumptions of coagulation factors, including II, V, VII, and X, and the breakdown of the endothelial barrier, respectively. Further research is necessary to investigate the robust coagulopathy system of sepsis, organ dysfunction, and HAT, or hydrocortisone, as a potential treatment for those with poor predicted outcomes.