Lovelace Biomedical Research Institute, Albuquerque, NM, USA.
Department of Neurology, University of New Mexico School of Medicine, Albuquerque, NM, USA.
Adv Exp Med Biol. 2024;1463:203-207. doi: 10.1007/978-3-031-67458-7_34.
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.
脓毒症导致感染性休克和多器官功能障碍综合征，其特征为炎症、凝血功能障碍和微血管功能障碍，是院内死亡的主要原因。需要新的方法来预防脓毒症的后果。我们曾表明，血管内血液可溶性减阻聚合物（DRP）的纳摩尔浓度可显著改善创伤性脑损伤和失血性休克后大鼠的微血管灌注和组织氧合，并保护其神经元。本研究旨在确定 DRP 增强的灌注是否可以缓解脂多糖（LPS）诱导的脓毒症小鼠模型中与脓毒症相关的微血管失调。通过静脉内给予 LPS（沙门氏菌 Typhosa，10mg/kg，iv.）来诱导 C57BL/6 J 小鼠的急性脓毒症。在 LPS 注射后 1 小时，通过静脉内注射 DRP（血液中的终浓度为 5ppm）或盐水（每组 10 只小鼠），以评估对微血管失调的血液流变学调节的疗效。通过活体双光子激光扫描显微镜监测大脑（顶叶皮层）和外周（耳朵）微循环（静脉内荧光素异硫氰酸酯葡聚糖）和组织氧供应（烟酰胺腺嘌呤二核苷酸自发荧光），在脓毒性休克诱导后 4 小时内进行。使用双向方差分析比较组间差异，并进行事后检验。统计学意义设定为 p < 0.05。LPS 诱导的脓毒症导致大脑和外周组织（耳朵）中的微血管功能障碍和组织缺氧。与盐水对照组相比，DRP 减轻了大脑和外周组织中的微血栓形成、微血管功能障碍和组织缺氧（p < 0.05）。因此，DRP 对血流的血液流变学调节可有效改善全身和外周循环，减少微血栓形成、微血管功能障碍和组织缺氧，从而缓解脓毒症、休克和多器官功能障碍综合征。
