Alleviation of Post-sepsis Ischaemia by Drag-Reducing Polymers

Sepsis, leading to septic shock and multiple organ dysfunction syndrome, is characterised by inflammation, coagulopathy, and microvascular dysfunction, the primary cause of in-hospital mortality. Novel approaches are needed to prevent the consequences of sepsis. We showed that nanomolar concentrations of intravascular blood-soluble drag-reducing polymers (DRPs) significantly improve microvascular perfusion and tissue oxygenation and protect neurons in rat brains after traumatic brain injury and haemorrhagic shock. The aim of this work was to determine whether DRPs-enhanced perfusion could alleviate sepsis-associated microvascular dysregulation in a mouse model of lipopolysaccharide (LPS)-induced sepsis. LPS (Salmonella Thyphosa, 10 mg/kg, i.v.) was administered intravenously to induce acute sepsis in C57BL/6 J mice. DRPs (final concentration 5 ppm in the blood) or saline was injected i.v. (10 mice/group) 1 h after LPS injection to evaluate the efficacy of haemorheological modulation of microvascular dysregulation. In-vivo two-photon laser scanning microscopy was used to monitor cerebral (parietal cortex) and peripheral (ear) microcirculation (i.v. fluorescein isothiocyanate dextran) and tissue oxygen supply (nicotinamide adenine dinucleotide autofluorescence) at a baseline and during 4 h after septic shock induction. Differences between groups were determined using a two-way analysis of variance for multiple comparisons with post hoc testing. The statistical significance was set at p < 0.05. LPS-induced sepsis led to microvascular dysfunction and tissue hypoxia in the brain and peripheral tissue (ear). DRPs alleviated microthrombosis formation, microvascular dysfunction, and tissue hypoxia in the brain and peripheral tissue compared to the saline control group (p < 0.05). Therefore, haemorheological modulation of blood flow by DRPs effectively improves systemic and peripheral circulation, reducing microthrombosis formation, microvascular dysfunction, and tissue hypoxia that can alleviate sepsis, shock, and multiple organ dysfunction syndrome.