Received June 11, 2018; Accepted September 30, 2018; Published October 30, 2018
http://dx.doi.org/10.18081/2333-5106/018-323-335
Peter Weighardt; Niels Hayashi; Gordon Medzhitov; Sean Newcomb
Abstract
In septic patients, the peculiarity of the systemic inflammatory response syndrome is both in terms of host defense and in terms of decreased defensive capacities, such that it ultimately resembles the clinical picture of multiple organ failure (MOF). Experimental models were employed to investigate the effects of heparin and performed experiments in two stages. Initially, male mice (C57BL/6) subjected to caecal slurry-induced sepsis were used to examine the severity of injury, specifically kidney injury, during a continuous intravenous heparin infusion. Prior to that, to monitor the levels and half-life of heparin, healthy male mice were treated with heparin intravenously. The levels of creatine, cystatin-c, blood urea nitrogen, and heparin in the kidney, heart, and liver were determined. All parameters, compared to control mice treated with saline, increased substantially in the kidneys of caecal slurry mice that were treated with heparin. Inflammatory indicators, especially interleukin-6 and interleukin-1 beta, are most increased in the kidneys, another sign of exacerbated organ damage. Administration of heparin during sepsis exacerbates organ damage, particularly in the kidney. Specifically, we compared the effects of caecal slurry – a clinically more relevant model of polymicrobial genital infections – in mice treated intravenously continuously with saline for 4 days with mice treated with heparin. Subsequently, heparin dosage was carried out based on the expulsion experiment, where C57BL/6 men were treated intravenously with saline for heparin to investigate the half-life and level of heparin. To investigate the effects of heparin, the creation and release of cystatin C, blood urea nitrogen (BUN), then creatine were accessed in the kidney, heart, and kidney. Overall, testing in two organs, the liver, found an increase in the number of parameters. More critically, a massive increase in the kidney nutrient was found in the kidneys of these animals. The best pro-inflammatory cytokines, including IL-6 and IL-1β, in heparin statistical forms are reduced, reflecting the enhanced immune function test. These data show that heparin can reduce collagen injury in the area, so it’s probably never used in a different way to do animals during the infection.
Keywords: Sepsis; Acute kidney injury (AKI); Heparin; Cytokine; LPS
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