Injurious Mechanical Ventilation and End-Organ Epithelial Cell Apoptosis and Organ Dysfunction in an Experimental Model of Acute Respiratory Distress Syndrome

Imai, Yumiko; Parodo, Jean; Kajikawa, Osamu; Perrot, Marc de; Fischer, Stefan; Edwards, Vern; Cutz, Ernest; Liu, Mingyao; Keshavjee, Shaf; Martin, Thomas R.; Marshall, John C.; Ranieri, V. Marco; Slutsky, Arthur S.

doi:10.1001/jama.289.16.2104

Cited by 621 publications

(417 citation statements)

References 51 publications

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“…The decreased influx of sodium from the lumen into the cells (induced by the lower levels of human ENaC), together with the increased influx of sodium from the interstitial space into the cells (induced by the higher levels of NKCC1), can block the net influx of sodium and water from the alveoli (30). These effects would be expected to increase susceptibility to ventilator-induced lung injury, an entity that is of increasing concern in intensive care settings (31,32).…”

Section: Discussionmentioning

confidence: 99%

Door-to-Dialysis Time and Daily Hemodialysis in Patients with Leptospirosis

Andrade

Cleto

Seguro

2007

Clinical Journal of the American Society of Nephrology

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Background: Leptospirosis is a public health problem, the severe form of which (Weil's disease) includes acute respiratory distress syndrome, typically accompanied by acute kidney injury (AKI), and is associated with high mortality rates. Recent evidence suggests that dialysis dosage affects outcomes in critically ill patients with sepsis-induced AKI. However, this population varies widely in terms of age, gender, and concomitant conditions, making it difficult to determine the appropriate timing (door-to-dialysis time) and dialysis dosage.Design, setting, participants, and measurements: It is logical to assume that increasing the dialysis dosage would minimize uremic complications and improve outcomes in such patients. Patients with Weil's disease constitute a homogeneous population and are typically free of comorbidities, therefore presenting an ideal model in which to test this assumption.Results Conclusions: On the basis of this result, it is believed that alternate-day hemodialysis is no longer appropriate for critically ill patients with Weil's disease.

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Section: Discussionmentioning

confidence: 99%

Door-to-Dialysis Time and Daily Hemodialysis in Patients with Leptospirosis

Andrade

Cleto

Seguro

2007

Clinical Journal of the American Society of Nephrology

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“…However, both in vitro and in situ observations await independent confirmation. For example, Imai and colleagues emphasize ATII necrosis in a rabbit model of ventilatorinjured lungs (39).…”

Section: Definition Of Abbreviationsmentioning

confidence: 99%

Hypercapnic Acidosis Impairs Plasma Membrane Wound Resealing in Ventilator-injured Lungs

Doerr

Gajić

Berríos

et al. 2005

Am J Respir Crit Care Med

118

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The objective of this study was to assess the effects of hypercapnic acidosis on lung cell injury and repair by confocal microscopy in a model of ventilator-induced lung injury. Three groups of normocapnic, hypocapnic, and hypercapnic rat lungs were perfused ex vivo, either during or after injurious ventilation, with a solution containing the membrane-impermeant label propidium iodide. In lungs labeled during injurious ventilation, propidium iodide fluorescence identifies all cells with plasma membrane wounds, both permanent and transient, whereas in lungs labeled after injurious ventilation propidium iodide fluorescence identifies only cells with permanent plasma membrane wounds. Hypercapnia minimized the adverse effects of high-volume ventilation on vascular barrier function, whereas hypocapnia had the opposite effect. Despite CO 2 -dependent differences in lung mechanics and edema the number of injured subpleural cells per alveolus was similar in the three groups (0.48 Ϯ 0.34 versus 0.51 Ϯ 0.19 versus 0.43 Ϯ 0.20 for hypocapnia, normocapnia, and hypercapnia, respectively). However, compared with normocapnia the probability of wound repair was significantly reduced in hypercapnic lungs (63 versus 38%; p Ͻ 0.02). This finding was subsequently confirmed in alveolar epithelial cell scratch models. The potential relevance of these observations for lung inflammation and remodeling after mechanical injury is discussed.Keywords: permissive hypercapnia; plasma membrane wounding and repair; ventilator-induced lung injury So-called lung protective mechanical ventilation strategies emphasize lung recruitment and the avoidance of large tidal volumes. Such strategies are often associated with hypercapnic acidosis. Many experts view "permissive hypercapnia" as a necessary evil of a low tidal ventilation strategy (1). Concern about detrimental effects of acidemia on renal and cardiovascular function have motivated attempts to enhance CO 2 removal by tracheal gas insufflation (2) and have led to unsubstantiated recommendations about the use of bicarbonate buffers in hypercapnic patients (3). More recent data suggest that hypercapnia may actually protect the lung from certain manifestations of ischemiareperfusion, endotoxin, and mechanical ventilation-related injury (4-9). Hypocapnia, in contrast, and correction of acidemia may be harmful (10-12). The specific mechanisms through which hypercapnia influences lung injury and vascular barrier function remain uncertain (13). CO 2 generates H ϩ ions, which react with titratable groups in certain amino acids and/or interacts directly (Received in original form September 3, 2003; accepted in final form January 21, 2005) Supported by grants from the National Institutes of Health (HL-63178), GlaxoSmithKline, and the Brewer Foundation. with free amine groups in proteins to form carbamate residues (14-16). CO 2 -dependent effects on the generation of reactive oxygen species and reactive nitrogen species as well as effects on ion channel conductivity have all been considered (17, 18).V...

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“…1,2 The primarily biological mechanisms include the release of inflammatory mediators and oxygen radicals, leading to end-organ epithelial cell apoptosis and organ dysfunction. [3][4][5] In a previous study, a high tidal volume in mouse lung could induce the activation of c-Jun N-terminal kinase (JNK), an increase in macrophage inflammatory protein-2 (MIP-2) expression, and the migration of neutrophil into the lung. 6 Activated JNK is dependent on the activation of apoptosis signal-related kinase 1 (ASK1), which is identified as a member of the mitogen-activated protein kinase (MAPK) family, in cultured bronchial epithelium.…”

Section: Introductionmentioning

confidence: 99%

Hypercapnic acidosis confers antioxidant and anti-apoptosis effects against ventilator-induced lung injury

Yang

Song

Wang

et al. 2013

Laboratory Investigation

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Hypercapnic acidosis may attenuate ventilator-induced lung oxidative stress injury and alveolar cell apoptosis, but the underlying mechanisms are poorly understood. We examined the effects of hypercapnic acidosis on the role of apoptosis signal-regulating kinase 1 (ASK1), which activates the c-Jun N-terminal kinase (JNK) and p38 cascade in both apoptosis and oxidative reactions, in high-pressure ventilation stimulated rat lungs. Rats were ventilated with a peak inspiratory pressure (PIP) of 30 cmH 2 O for 4 h and randomly given FiCO 2 to achieve normocapnia (PaCO 2 at 35-45 mm Hg) or hypercapnia (PaCO 2 at 80-100 mm Hg); normally ventilated rats with PIP of 15 cmH 2 O were used as controls. Lung injury was quantified by gas exchange, microvascular leaks, histology, levels of inflammatory cytokines, and pulmonary oxidative reactions. Apoptosis through the ASK1-JNK/p38 mitogen-activated protein kinase (MAPK) cascade in type II alveolar epithelial cells (AECIIs) were evaluated by examination of caspase-3 activation. The results showed that injurious ventilation caused significant lung injury, including deteriorative oxygenation, changes of histology, and the release of inflammatory cytokines. In addition, the high-pressure mechanical stretch also induced apoptosis and caspase-3 activation in the AECIIs. Hypercapnia attenuated these responses, suppressing the ASK1 signal pathways with its downstream kinase phosphorylation of p38 MAPK and JNK, and caspase-3 activation. Thus, hypercapnia can attenuate cell apoptosis and oxidative stress damage in rat lungs during injurious ventilation, at least in part, due to the suppression of the ASK1-JNK/p38 MAPK pathways.

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Injurious Mechanical Ventilation and End-Organ Epithelial Cell Apoptosis and Organ Dysfunction in an Experimental Model of Acute Respiratory Distress Syndrome

Cited by 621 publications

References 51 publications

Door-to-Dialysis Time and Daily Hemodialysis in Patients with Leptospirosis

Door-to-Dialysis Time and Daily Hemodialysis in Patients with Leptospirosis

Hypercapnic Acidosis Impairs Plasma Membrane Wound Resealing in Ventilator-injured Lungs

Hypercapnic acidosis confers antioxidant and anti-apoptosis effects against ventilator-induced lung injury

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