Association between Maturation and Aging and Pulmonary Responses in Animal Models of Lung Injury

Schouten, Laura R. A.; Schultz, Marcus J.; Kaam, Anton H. van; Juffermans, Nicole P.; Bos, Albert P.; Asperen, Roelie M. Wösten–van

doi:10.1097/aln.0000000000000687

Cited by 32 publications

(33 citation statements)

References 95 publications

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“…Besides, most experiments use young male rodents that almost never have comorbidities for the evaluation of new treatments for ARDS, while patient populations seen in intensive care units are elderly and frequently have concomitant diseases such as diabetes mellitus, chronic obstructive pulmonary disease or active cancer [54]. The few studies that compared elderly rodents to younger ones indeed found a difference in the biological response between these groups [55,56].…”

Section: Ineffective Interventionsmentioning

confidence: 99%

ARDS: challenges in patient care and frontiers in research

2018

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This review discusses the clinical challenges associated with ventilatory support and pharmacological interventions in patients with acute respiratory distress syndrome (ARDS). In addition, it discusses current scientific challenges facing researchers when planning and performing trials of ventilatory support or pharmacological interventions in these patients.Noninvasive mechanical ventilation is used in some patients with ARDS. When intubated and mechanically ventilated, ARDS patients should be ventilated with low tidal volumes. A plateau pressure <30 cmH 2 O is recommended in all patients. It is suggested that a plateau pressure <15 cmH 2 O should be considered safe. Patient with moderate and severe ARDS should receive higher levels of positive endexpiratory pressure (PEEP). Rescue therapies include prone position and neuromuscular blocking agents. Extracorporeal support for decapneisation and oxygenation should only be considered when lungprotective ventilation is no longer possible, or in cases of refractory hypoxaemia, respectively. Tracheotomy is only recommended when prolonged mechanical ventilation is expected.Of all tested pharmacological interventions for ARDS, only treatment with steroids is considered to have benefit.Proper identification of phenotypes, known to respond differently to specific interventions, is increasingly considered important for clinical trials of interventions for ARDS. Such phenotypes could be defined based on clinical parameters, such as the arterial oxygen tension/inspiratory oxygen fraction ratio, but biological marker profiles could be more promising.

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Section: Ineffective Interventionsmentioning

confidence: 99%

ARDS: challenges in patient care and frontiers in research

2018

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“…У детей важно проводить тщательный интраоперационный мониторинг с контролем глюкозы крови в течение оперативного вмешательства [17,18], чтобы обеспечить нормогликемию.…”

Section: результаты и обсуждениеunclassified

Strategy of Infusion-Transfusion Therapy in Operations With Massive Bloodwork in Children With Tumor Abomalomal Localization Tumors

Белоусова

Матинян

Martynov

2018

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Surgeries for thoracoabdominal tumors in children predispose to water and electrolyte imbalance, imbalance in the coagulation system, etc. In spite of abundance of recommendations for children, the volume of basic infusion therapy is uncertain.Study purpose. To estimate the clinical effectiveness of the conducted infusion therapy with isotonic balanced electrolyte solution in children who underwent thoracoabdominal surgeries accompanied with massive blood loss and a complex estimation of the conducted infusion and transfusion therapy.Materials and methods. The intraoperative and early postoperative (days 1–5) periods were analyzed in 22 patients (ASA II–III) who underwent an operation for thoracoabdominal malignant tumors with massive perioperative blood loss in 2016–2017. Group I included 11 patients who had infusion with balanced crystalloid solutions of 5 to 10 ml/kg/hour under combined anesthesia. Group II includes 11 patients who had infusion with balanced crystalloid solutions of 11 to 20 ml/kg/hour under combined anesthesia.Results. According to the conducted study, a higher hemodynamic stability was observed in patients from the group of basic infusion therapy with balanced crystalloid solutions of 11–20 ml/kg/hour. It was expressed as the decrease of the mean dose of the used vasopressors and volume of the infusion of colloidal solutions. The patients also had a less intense response to stress.

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“…Mortality rates and hospital discharge to extended care facilities increased consistently for each decade of age over the age of 65 years in mechanically ventilated patients (22). Epidemiological studies also suggest that age is a predictive factor in the severity of VILI; however, the exact molecular mechanisms between age and VILI are still unknown (16, 55, 63). In rodent models of VILI, we and others have shown that age increases susceptibility to ventilator-induced edema, injury, and mortality (1, 36).…”

Section: Introductionmentioning

confidence: 99%

Inflammation and Monocyte Recruitment Due to Aging and Mechanical Stretch in Alveolar Epithelium are Inhibited by the Molecular Chaperone 4-Phenylbutyrate

et al. 2018

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Introduction Ventilator-Induced lung injury (VILI) is a form of acute lung injury that is initiated or exacerbated by mechanical ventilation. The aging lung is also more susceptible to injury. Harmful mechanical stretch of the alveolar epithelium is a recognized mechanism of VILI, yet little is known about how mechanical stretch affects aged epithelial cells. Disruption to Endoplasmic Reticulum (ER) homeostasis results in a condition known as ER stress that leads to disruption of cellular homeostasis, apoptosis, and inflammation. ER stress is increased with aging and other pathological stimuli. We hypothesized that age and mechanical stretch increase alveolar epithelial cells’ proinflammatory responses that are mediated by ER stress. Furthermore, we believed that inhibition of this upstream mechanism with 4PBA, an ER stress reducer, alleviates subsequent inflammation and monocyte recruitment. Methods Type II alveolar epithelial cells (ATII) were harvested from C57Bl6/J mice 2 months (young) and 20 months (old) of age. The cells were cyclically stretched at 15% change in surface area for up to 24 hours. Prior to stretch, groups were administered 4PBA or vehicle as a control. Results Mechanical stretch and age upregulated ER stress and proinflammatory MCP-1/CCL2 and MIP-1β/CCL4 chemokine expression in ATIIs. Age-matched and mismatched monocyte recruitment by ATII conditioned media was also quantified. Conclusions Age increases susceptibility to stretch-induced ER stress and downstream inflammatory gene expression in a primary ATII epithelial cell model. Administration of 4PBA attenuated the increased ER stress and proinflammatory responses from stretch and/or age and significantly reduced monocyte migration to ATII conditioned media.

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Association between Maturation and Aging and Pulmonary Responses in Animal Models of Lung Injury

Cited by 32 publications

References 95 publications

ARDS: challenges in patient care and frontiers in research

ARDS: challenges in patient care and frontiers in research

Strategy of Infusion-Transfusion Therapy in Operations With Massive Bloodwork in Children With Tumor Abomalomal Localization Tumors

Inflammation and Monocyte Recruitment Due to Aging and Mechanical Stretch in Alveolar Epithelium are Inhibited by the Molecular Chaperone 4-Phenylbutyrate

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