Effect of Free Radical Scavengers on Diaphragmatic  Contractility in Septic Peritonitis

Fujimura, Naoyuki; Sumita, Shinichi; Aimono, Mako; Masuda, Yoshiki; Shichinohe, Yasuo; Narimatsu, Eichi; Namiki, Akiyoshi

doi:10.1164/ajrccm.162.6.9912144

Cited by 63 publications

(47 citation statements)

References 29 publications

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“…Pulmonary inflammation and consequent injury is linked to systemic inflammation in patients with COPD, 29 and increased circulating inflammatory markers have been detected in CF subjects. 30,31 Infection induces respiratory muscle weakness in animal models, 32 and respiratory muscle weakness is associated with upper-respiratory-tract infections in humans. 33 Induced chronic bronchopulmonary infection by P. aeruginosa significantly decreased diaphragm and limb strength in infected mice, 28 and tumor necrosis factor alpha depressed the diaphragmatic tetanic force in murine diaphragm and limb muscle preparations.…”

Section: Discussionmentioning

confidence: 99%

ChronicPseudomonas aeruginosaInfection and Respiratory Muscle Impairment in Cystic Fibrosis

et al. 2013

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BACKGROUND: Chronic infection with Pseudomonas aeruginosa in patients with cystic fibrosis (CF) is associated with increased morbidity. Chronic infection can cause limb and respiratory muscle compromise. Respiratory muscle function can be assessed via maximal inspiratory pressure (P Imax ), maximal expiratory pressure (P Emax ), and the pressure-time index of the respiratory muscles (PTI mus ). We studied the effect of chronic P. aeruginosa infection on respiratory muscle function in patients with CF. METHODS: This cross-sectional study assessed P Imax , P Emax , PTI mus , FEV 1 , FVC, maximum expiratory flow during the middle half of the FVC maneuver, body mass index, and upper arm muscle area in 122 subjects with CF, in 4 subgroups matched for age and sex at different stages of P. aeruginosa infection, according to the Leeds criteria. We compared respiratory muscle function in the subgroups according to P. aeruginosa infection state. RESULTS: Median P Imax was significantly lower in CF subjects with chronic P. aeruginosa infection (P Imax ‫؍‬ 62 cm H 2 O), compared to subjects who were never infected (P Imax ‫؍‬ 86 cm H 2 O, P ‫؍‬ .02), free of infection (P Imax ‫؍‬ 74 cm H 2 O, P ‫؍‬ .01), or intermittently infected (P Imax ‫؍‬ 72 cm H 2 O, P ‫؍‬ .02). Median PTI mus was significantly increased in CF subjects with chronic P. aeruginosa infection (PTI mus ‫؍‬ .142), compared to subjects who were free of infection (PTI mus ‫؍‬ .102, P ‫؍‬ .006). Median upper-arm muscle area was significantly lower in CF subjects with chronic P. aeruginosa infection (upper-arm muscle area ‫؍‬ 2,219 mm 2 ), compared to subjects who were never infected (2,754 mm 2 , P ‫؍‬ .03), free of infection (2,678 mm 2 , P ‫؍‬ .01), or intermittently infected (2,603 mm 2 , P ‫؍‬ .04). Multivariate logistic regression revealed P. aeruginosa state of infection as a significant determinant of PTI mus (P ‫؍‬ .03) independently of sex, upper-arm muscle area, and FEV 1 . CON-CLUSIONS: CF subjects with chronic P. aeruginosa infection exhibited impaired respiratory muscle function and decreased inspiratory muscle strength, and chronic P. aeruginosa infection independently impacts respiratory muscle function in subjects with CF.

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Section: Discussionmentioning

confidence: 99%

ChronicPseudomonas aeruginosaInfection and Respiratory Muscle Impairment in Cystic Fibrosis

et al. 2013

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“…Since in septic patients cAMP stores were found depleted (54), the authors also speculated that phosphodiesterase inhibition would alleviate fatigue patterns. Using the PDE inhibitor olprinone, both MPO activity and fatigue were restored similarly towards control levels, indicating a crucial involvement of activated neutrophils or macrophages within septic tissue to contribute to downstream muscle weakness and increased fatigability, probably through their cytokine release patterns of IL-1 and TNF-␣ or free radicals (94,224,488). In chronic inflammatory conditions of polymyositis and dermatomyositis, muscle weakness in patients was correlated with a strong expression of IL-1␣ in patient muscle tissues (516).…”

Section: E Muscle Fatigue In Critical Illnessmentioning

confidence: 96%

The Sick and the Weak: Neuropathies/Myopathies in the Critically Ill

Friedrich

Reid

Berghe

et al. 2015

Physiological Reviews

300

329

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Critical illness polyneuropathies (CIP) and myopathies (CIM) are common complications of critical illness. Several weakness syndromes are summarized under the term intensive care unit-acquired weakness (ICUAW). We propose a classification of different ICUAW forms (CIM, CIP, sepsis-induced, steroid-denervation myopathy) and pathophysiological mechanisms from clinical and animal model data. Triggers include sepsis, mechanical ventilation, muscle unloading, steroid treatment, or denervation. Some ICUAW forms require stringent diagnostic features; CIM is marked by membrane hypoexcitability, severe atrophy, preferential myosin loss, ultrastructural alterations, and inadequate autophagy activation while myopathies in pure sepsis do not reproduce marked myosin loss. Reduced membrane excitability results from depolarization and ion channel dysfunction. Mitochondrial dysfunction contributes to energy-dependent processes. Ubiquitin proteasome and calpain activation trigger muscle proteolysis and atrophy while protein synthesis is impaired. Myosin loss is more pronounced than actin loss in CIM. Protein quality control is altered by inadequate autophagy. Ca 2ϩ dysregulation is present through altered Ca 2ϩ homeostasis. We highlight clinical hallmarks, trigger factors, and potential mechanisms from human studies and animal models that allow separation of risk factors that may trigger distinct mechanisms contributing to weakness. During critical illness, altered inflammatory (cytokines) and metabolic pathways deteriorate muscle function. ICUAW prevention/treatment is limited, e.g., tight glycemic control, delaying nutrition, and early mobilization. Future challenges include identification of primary/secondary events during the time course of critical illness, the interplay between membrane excitability, bioenergetic failure and differential proteolysis, and finding new therapeutic targets by help of tailored animal models.

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“…In the sham-operated control groups YES, after laparotomy, the cecum was manipulated but left intact (without ligation or perforation). In the S group, rats underwent CLP according to the method described by Fujimura et al (17).…”

Section: Experimental Protocol and Sepsis Inductionmentioning

confidence: 99%

Effect of an Aqueous Garlic Extract on Kidney Damage in an Experimental Model of Sepsis

Ipekci¹,

Tunalı-Akbay²,

Şener³

2017

Clin Exp Health Sci

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Amaç: Sepsis, patojenlere veya onların salgıladığı maddelere karşı verilen sistemik inflamatuvar bir yanıttır. Bu çalışmada sepsiste oluşan böbrek hasarına karşı sulu sarımsak ekstresinin olası koruyucu etkisi incelenmiştir. Yöntemler: Çalışmamızda sıçanlar; 'kontrol' , 'sepsis' , 'sepsis+sarımsak' ve 'sepsis+ön-tedavili sarımsak' grupları olmak üzere 4 gruba ayrılmıştır. Sepsis modeli çekal ligasyon ve perforasyon yöntemi ile oluşturulmuştur. 'Sepsis+ön-tedavili sarımsak' grubuna sepsis oluşumundan 15 gün önce başlanarak, 250 mg/kg/gün dozunda sulu sarımsak ekstresi oral yoldan uygulanmıştır. 'Sepsis+sarımsak' grubunda ise tedavi sepsis uygulamasından hemen sonra tek doz (250 mg/kg) olarak yapılmıştır. Sepsis oluşumundan 12 saat sonra bütün gruplardaki sıçanlar dekapite edilerek, böbrek dokuları alınmıştır. Böbrek dokusunda, glutatyon (GSH) ve malondialdehit (MDA) seviyeleri, süperoksit dismutaz (SOD), doku faktörü (TF), katalaz (CAT) ve miyeloperoksidaz (MPO) aktivitesi tayin edilmiştir. Bulgular: Sepsise bağlı olarak böbrek dokusunda artan MDA düzeyleri ve MPO aktivitesi ile azalan GSH düzeyleri ve SOD ve CAT aktiviteleri sulu sarımsak ekstresi ile geri çevrilmiştir. TF aktivitesi sepsiste değişmemiştir. Kısalmış pıhtı oluşum zamanı, artmış TF aktivitesini göstermektedir. Bu doğrultuda ön-tedavili sepsis sarımsak grubunda TF aktivitesi artmıştır. Sonuç: Sulu sarımsak ekstresi kullanımının yeni sepsis tedavi yöntemleri geliştirilirken oksidan-antioksidan dengesi açısından dikkate alınması gerektiğini düşünmekteyiz.

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Effect of Free Radical Scavengers on Diaphragmatic Contractility in Septic Peritonitis

Cited by 63 publications

References 29 publications

ChronicPseudomonas aeruginosaInfection and Respiratory Muscle Impairment in Cystic Fibrosis

ChronicPseudomonas aeruginosaInfection and Respiratory Muscle Impairment in Cystic Fibrosis

The Sick and the Weak: Neuropathies/Myopathies in the Critically Ill

Effect of an Aqueous Garlic Extract on Kidney Damage in an Experimental Model of Sepsis

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