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. METHOD(S): 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 posthoc testing using the Mann-Whitney U-test. RESULT(S): 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). CONCLUSION(S): Hemorheological modulation of blood flow by DRP effectively improves systemic and peripheral circulation, reducing microthrombosis formation, inflammation and microvascular dysfunction, alleviating sepsis and MODS.
ABSTRACT
BACKGROUND: The COVID-19 pandemic has substantially contributed to increased anxiety rates among the general population worldwide. Pandemic-related health anxiety and worries about getting COVID-19 can lead to generalized anxiety and anxiety somatization, which, together with insalubrious daily life habits, are risk factors of worsening somatic health in people with SARS-Cov-2 infection. SUBJECTS AND METHODS: The current study is a part of the COMET-G project (40 countries, n=55589;approved by the Ethics Committee of the Aristotle University of Thessaloniki), which represents an intermediate analysis of data collected anonymously via online links from a national sample of the Russian general population (n=9936, 31.09+/-12.16 y.o., 58.7% females) to estimate anxiety using STAI-S and self-reported changes in anxiety and life habits (physical activity, nutrition and weight, internet use, sleep) during the lockdown. All statistical calculations (descriptive statistics, between group comparisons using chi-square test, MANOVA, ANOVA, significant at p<0.05) were performed with IBM SPSS 27. RESULTS: Overall STAI-S scores were 29+/-5.4, a subjective feeling of anxiety increase was reported in 40.3% of respondents (43.9% significantly > in females), worsening to clinical anxiety in 2.1% (2.4% > in females). 54.2% of respondents reported decreased physical activity, 33.1% gained weight, 72% used internet more often, 52.6% experienced worries related to the information about COVID-19 (56.8% > in females). 88% experienced worsened sleep quality, 69.2% stayed up until late, 23.2% took sleeping pills, and 31% had nightmares in which they felt trapped. To ANOVA, such life habits as reduced physical activity during the lockdown, increased time spent online, internet browsing about COVID-19, tendency to stay up late, use of sleeping pills and disturbing dreams with scenario of being trapped were significantly related to worsening of clinical anxiety. However, eating behaviour, weight changes, and social media use did not contribute to the clinical anxiety increase. CONCLUSIONS: Factors of decreased physical activity and sleep disturbances related to the lockdown, as well as excessive internet browsing for information about COVID-19, emerged as risk factors for increased anxiety, more notably in women than in men. Preventive measures should be targeted against relevant factors imparting anxiety in the vulnerable population.