Calcium-dependent phospholipase A<sub>2</sub>modulates infection-induced diaphragm dysfunction

Supinski, Gerald S.; Alimov, Alexander P.; Wang, Lin; Song, Xiaohong; Callahan, Leigh Ann

doi:10.1152/ajplung.00312.2015

Cited by 23 publications

(36 citation statements)

References 41 publications

(69 reference statements)

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“…Consistent with existing knowledge [ 1 , 2 , 30 – 32 ], our study found that sepsis with following CMV could make significant diaphragm injury in rat model. Moreover, since diaphragm contractile properties improvement with MgSO 4 administration after CLP was recorded in our study, we, therefore, assume the MgSO 4 therapeutic potential for sepsis-induced diaphragmatic dysfunction.…”

Section: Discussionsupporting

confidence: 92%

Magnesium sulfate ameliorates sepsis-induced diaphragm dysfunction in rats via inhibiting HMGB1/TLR4/NF-κB pathway

Jiang

Chen

et al. 2020

NeuroReport

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Background Diaphragm dysfunction could be induced by sepsis with subsequent ventilatory pump failure that is associated with local infiltration of inflammatory factors in the diaphragm. It has been shown that the administration of anticonvulsant agent, magnesium sulfate (MgSO 4 ) could decrease systematic inflammatory response. We recently reported that MgSO 4 could inhibit macrophages high mobility group box 1 (HMGB1) secretion that confirms its anti-inflammatory properties. Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signal pathway appears to be involved in the pathology of septic experimental animal’s inflammatory response and involve in the pathogenic mechanisms of sepsis-induced diaphragm dysfunction. Thus, in this study, we are aiming to explore whether MgSO 4 could ameliorate sepsis-induced diaphragm dysfunction via TLR4/NF-κB pathway in a rodent model with controlled mechanical ventilation (CMV) and subsequent septic challenge. Methods Rats were randomly assigned into (1) control group: having an identical laparotomy but without ligation or puncture in the cecum; (2) CLP group: cecal ligation and puncture (CLP) with continuous saline infusion; (3) CLP + MgSO 4 group: CLP with continuous MgSO 4 administration; and (4) MgSO 4 group: a sham surgery with MgSO 4 administration. After surgery, all rats were submitted to CMV for 18 h. After completion of the study protocol, blood inflammatory cytokine/chemokine was detected by ELISA, as well as diaphragm contractility, TLR4, NF-κB (p65), phospho-NF-κB (p65) and HMGB1 protein expression. Results The level of inflammatory cytokine/chemokine includes interleukin-6, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-2 (MIP-2) and HMGB1 in blood were significantly increased at 18-h post-CLP compared with the control group. We found that rats in the CLP group had substantial diaphragm dysfunction with a distinct downshift of the force–frequency curve. Furthermore, expression of HMGB1, TLR4, NF-κB (p65) and phospho-NF-κB (p65) in diaphragm were significantly increased in the CLP group. In contrast, MgSO 4 attenuated the septic inflammation reaction in diaphragm and serum and preserved diaphragm function. Conclusion MgSO 4 protects against sepsis-induced diaphragm dysfunction. This may be associated with its anti-inflammatory effect on HMGB1/TLR4/NF-κB signal pathway

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Section: Discussionsupporting

confidence: 92%

Magnesium sulfate ameliorates sepsis-induced diaphragm dysfunction in rats via inhibiting HMGB1/TLR4/NF-κB pathway

Jiang

Chen

et al. 2020

NeuroReport

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“…Nonencapsulated heme is an important injurious agent in several pathologies such as the endothelial injury after lipopolysaccharide exposure (26), lung injury after Libby amphibole asbestos exposure (27), hyperoxia-induced lung injury (28), pulmonary hypertension in sickle cell anemia (29), and trauma-hemorrhage (30). Nonencapsulated heme causes oxidative stress by generating reactive species and redox-active iron capable of initiating lipid peroxidation (31,32). It intercalates into cell membranes and causes oxidative loss of plasma membrane integrity (33).…”

Section: Introductionmentioning

confidence: 99%

Heme scavenging reduces pulmonary endoplasmic reticulum stress, fibrosis, and emphysema

Aggarwal¹,

Ahmad²,

Lam³

et al. 2018

JCI Insight

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“…Pathophysiological mechanisms of DW are usually classified as infection/inflammation-related or ventilator-induced mechanisms 33, 34 . Infection causes cytokine release, which in turn induces mitochondrial free radical production 35, 36 , contributing to the reduction in muscle endurance and strength 36 . Histopathological findings include injury of the muscle fibers with disrupted sarcomeres 37, 38 .…”

Section: Diaphragmatic Weakness and Icu-aw: Different Clinical Entitimentioning

confidence: 99%

Intensive care unit–acquired weakness: unanswered questions and targets for future research

2019

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Intensive care unit–acquired weakness (ICU-AW) is the most common neuromuscular impairment in critically ill patients. We discuss critical aspects of ICU-AW that have not been completely defined or that are still under discussion. Critical illness polyneuropathy, myopathy, and muscle atrophy contribute in various proportions to ICU-AW. Diagnosis of ICU-AW is clinical and is based on Medical Research Council sum score and handgrip dynamometry for limb weakness and recognition of a patient’s ventilator dependency or difficult weaning from artificial ventilation for diaphragmatic weakness (DW). ICU-AW can be caused by a critical illness polyneuropathy, a critical illness myopathy, or muscle disuse atrophy, alone or in combination. Its diagnosis requires both clinical assessment of muscle strength and complete electrophysiological evaluation of peripheral nerves and muscles. The peroneal nerve test (PENT) is a quick simplified electrophysiological test with high sensitivity and good specificity that can be used instead of complete electrophysiological evaluation as a screening test in non-cooperative patients. DW, assessed by bilateral phrenic nerve magnetic stimulation or diaphragm ultrasound, can be an isolated event without concurrent limb muscle involvement. Therefore, it remains uncertain whether DW and limb weakness are different manifestations of the same syndrome or are two distinct entities. Delirium is often associated with ICU-AW but a clear correlation between these two entities requires further studies. Artificial nutrition may have an impact on ICU-AW, but no study has assessed the impact of nutrition on ICU-AW as the primary outcome. Early mobilization improves activity limitation at hospital discharge if it is started early in the ICU, but beneficial long-term effects are not established. Determinants of ICU-AW can be many and can interact with each other. Therefore, future studies assessing early mobilization should consider a holistic patient approach with consideration of all components that may lead to muscle weakness.

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Calcium-dependent phospholipase A₂modulates infection-induced diaphragm dysfunction

Abstract: Supinski GS, Alimov AP, Wang L, Song X, Callahan LA. Calciumdependent phospholipase A 2 modulates infection-induced diaphragm dysfunction.

Cited by 23 publications

References 41 publications

Magnesium sulfate ameliorates sepsis-induced diaphragm dysfunction in rats via inhibiting HMGB1/TLR4/NF-κB pathway

Magnesium sulfate ameliorates sepsis-induced diaphragm dysfunction in rats via inhibiting HMGB1/TLR4/NF-κB pathway

Heme scavenging reduces pulmonary endoplasmic reticulum stress, fibrosis, and emphysema

Intensive care unit–acquired weakness: unanswered questions and targets for future research

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Calcium-dependent phospholipase A2modulates infection-induced diaphragm dysfunction

Abstract: Supinski GS, Alimov AP, Wang L, Song X, Callahan LA. Calciumdependent phospholipase A 2 modulates infection-induced diaphragm dysfunction.

Cited by 23 publications

References 41 publications

Magnesium sulfate ameliorates sepsis-induced diaphragm dysfunction in rats via inhibiting HMGB1/TLR4/NF-κB pathway

Magnesium sulfate ameliorates sepsis-induced diaphragm dysfunction in rats via inhibiting HMGB1/TLR4/NF-κB pathway

Heme scavenging reduces pulmonary endoplasmic reticulum stress, fibrosis, and emphysema

Intensive care unit–acquired weakness: unanswered questions and targets for future research

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Calcium-dependent phospholipase A₂modulates infection-induced diaphragm dysfunction