1228: MITIGATION OF POST-SEPTIC MICROCIRCULATION DYSFUNCTION BY DRAG-REDUCING POLYMERS

Abstract

Introduction: Sepsis and septic shock in multiorgan dysfunction syndrome (MODS) are characterized by inflammation, coagulopathy, and vascular collapse with the endothelial and microvascular breakdown of endothelial function, the primary cause of mortality among hospitalized patients. We evaluated here whether drag-reducing polymers (DRP) can alleviate sepsis and MODS-associated panvascular dysregulation of microvascular blood flow using a mouse model of LPS-induced sepsis. Since the pathophysiology of MODS and Covid-19 share many characteristics in inflammation, coagulopathy, and low blood flow as a constellation of factors culminating in low microvascular shear rate and loss of endothelial function common to the pathophysiology of both diseases, the model utilized in this study also can be considered as the Covid-19 model. Methods: To induce acute sepsis and MODS, lipopolysaccharide (LPS-Salmonella Thyphosa) was injected i.v. (10 mg/kg) in C57BL/6J mice. In-vivo 2-photon laser scanning microscopy was used to monitor systemic cerebral (parietal cortex) and peripheral (ear) microcirculation, NADH (hypoxia), and oxidative stress. Blood samples obtained at autopsy were analyzed for Inflammation, coagulopathy, and endothelial glycocalyx disintegration biomarkers. Brain, lungs, kidney, liver, muscle, and intestine (rectum) were histologically evaluated. Differences between groups were determined using two-way ANOVA for multiple comparisons and post-hoc testing using the Mann-Whitney U-test. Results: LPS injection induced inflammatory reaction and microvascular dysfunction. DRP alleviated the inflammation, microthrombosis formation, and microvascular dysfunction in all organs evaluated (p< 0.05). Blood samples analysis by ELISA revealed reduced inflammation, coagulopathy, and endothelial glycocalyx disintegration in the DRP-treated group (p< 0.05). Conclusions: Hemorheological modulation of blood flow by DRP effectively improves systemic and peripheral circulation, reducing microthrombosis formation, inflammation and microvascular dysfunction, alleviating sepsis and MODS.