Lymphatic flow modulation as adjunct therapy for septic shock

Pruitt, Louis Gordon

doi:10.1016/j.mehy.2020.109748

Cited by 2 publications

(1 citation statement)

References 64 publications

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“…The role of PHSML in the pathogenesis of hemorrhagic shockcaused distant organ damage has received attention (41)(42)(43). Based on the fact that mesenteric lymph return after shock plays an indispensable role in the occurrence of ALI, to demonstrate that the effect of E2 in attenuating hemorrhagic shock-induced ALI is achieved through PHSML, this study applied an anesthetized rat hemorrhagic shock model for PHSML drainage, and then drained PHSML was intravenously injected to the E2-treated hemorrhagic shock rats.…”

Section: Discussionmentioning

confidence: 99%

Estrogen Alleviates Posthemorrhagic Shock Mesenteric Lymph-Mediated Lung Injury Through Autophagy Inhibition

Sun

Zhang

et al. 2023

Shock

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Background: Hemorrhagic shock–induced acute lung injury (ALI) is commonly associated with the posthemorrhagic shock mesenteric lymph (PHSML) return. Whether excessive autophagy is involved in PHSML-mediated ALI remains unclear. The relationship between estrogen treatment and PHSML or autophagy needs to verify. The current study will clarify the role of estrogen in reducing PHSML-mediated ALI through inhibition of autophagy. Methods: First, a hemorrhagic shock model in conscious rats was used to observe the effects of 17β-estradiol (E2) on intestinal blood flow, pulmonary function, intestinal and pulmonary morphology, and expression of autophagy marker proteins. Meanwhile, the effect of PHSML and autophagy agonist during E2 treatment was also investigated. Secondly, rat primary pulmonary microvascular endothelial cells were used to observe the effect of PHSML, PHSML plus E2, and E2-PHSML (PHSML obtained from rats treated by E2) on the cell viability. Results: Hemorrhagic shock induced intestinal and pulmonary tissue damage and increased wet/dry ratio, reduced intestinal blood flow, along with pulmonary dysfunction characterized by increased functional residual capacity and lung resistance and decreased inspiratory capacity and peak expiratory flow. Hemorrhagic shock also enhanced the autophagy levels in intestinal and pulmonary tissue, which was characterized by increased expressions of LC3 II/I and Beclin-1 and decreased expression of p62. E2 treatment significantly attenuated these adverse changes after hemorrhagic shock, which was reversed by PHSML or rapamycin administration. Importantly, PHSML incubation decreased the viability of pulmonary microvascular endothelial cells, while E2 coincubation or E2-treated lymph counteracted the adverse roles of PHSML. Conclusions: The role of estrogen reducing PHSML-mediated ALI is associated with the inhibition of autophagy.

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Section: Discussionmentioning

confidence: 99%

Estrogen Alleviates Posthemorrhagic Shock Mesenteric Lymph-Mediated Lung Injury Through Autophagy Inhibition

Sun

Zhang

et al. 2023

Shock

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Duodenum edema due to reduced lymphatic drainage leads to increased inflammation in a porcine endotoxemic model

Marchesi

Larsson

Hedenstierna

et al. 2022

ICMx

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Background Interventions, such as mechanical ventilation with high positive end-expiratory pressure (PEEP), increase inflammation in abdominal organs. This effect could be due to reduced venous return and impaired splanchnic perfusion, or intestinal edema by reduced lymphatic drainage. However, it is not clear whether abdominal edema per se leads to increased intestinal inflammation when perfusion is normal. The aim of the presented study was to investigate if an impaired thoracic duct function can induce edema of the abdominal organs and if it is associated to increase inflammation when perfusion is maintained normal. In a porcine model, endotoxin was used to induce systemic inflammation. In the Edema group (n = 6) the abdominal portion of the thoracic duct was ligated, while in the Control group (7 animals) it was maintained intact. Half of the animals underwent a diffusion weighted-magnetic resonance imaging (DW-MRI) at the end of the 6-h observation period to determine the abdominal organ perfusion. Edema in abdominal organs was assessed using wet–dry weight and with MRI. Inflammation was assessed by measuring cytokine concentrations in abdominal organs and blood as well as histopathological analysis of the abdominal organs. Results Organ perfusion was similar in both groups, but the Edema group had more intestinal (duodenum) edema, ascites, higher intra-abdominal pressure (IAP) at the end of observation time, and higher cytokine concentration in the small intestine. Systemic cytokines (from blood samples) correlated with IAP. Conclusions In this experimental endotoxemic porcine model, the thoracic duct’s ligation enhanced edema formation in the duodenum, and it was associated with increased inflammation.

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Lymphatic flow modulation as adjunct therapy for septic shock

Cited by 2 publications

References 64 publications

Estrogen Alleviates Posthemorrhagic Shock Mesenteric Lymph-Mediated Lung Injury Through Autophagy Inhibition

Estrogen Alleviates Posthemorrhagic Shock Mesenteric Lymph-Mediated Lung Injury Through Autophagy Inhibition

Duodenum edema due to reduced lymphatic drainage leads to increased inflammation in a porcine endotoxemic model

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