Repeated endo-tracheal tube disconnection generates pulmonary edema in a model of volume overload: an experimental study.

Background: An abrupt lung deflation in rodents results in lung injury through vascular mechanisms. Ventilator disconnections during endo-tracheal suctioning in humans often cause cardio-respiratory instability. Whether repeated disconnections or lung deflations cause lung injury or oedema is not known and was tested here in a porcine large animal model.

Impact of Reverse Triggering Dyssynchrony during Lung-Protective Ventilation on Diaphragm Function: An Experimental Model.

Reverse triggering dyssynchrony (RT) is a patient-ventilator interaction where a respiratory muscle contraction is triggered by a passive mechanical insufflation. Its impact on diaphragm structure and function is unknown. To establish an animal model of RT with lung injury receiving lung-protective ventilation and to assess its impact on the structure and function of the diaphragm.

Embryonic-Derived Macrophages Enhance Bacterial Clearance and Improve Survival in Rat Sepsis.

Peritoneal resident macrophages play a key role in combating sepsis in the peritoneal cavity. We sought to determine if peritoneal transplantation of embryonic "peritoneal-like" macrophages attenuate abdominal fecal sepsis. Directed differentiation of rodent pluripotent stem cells (PSCs) was used in factor-defined media to produce embryonic-derived large "peritoneal-like" macrophages (Ed-LPM) that expressed peritoneal macrophage markers and demonstrated phagocytic capacity.

Positive End-Expiratory Pressure, Pleural Pressure, and Regional Compliance during Pronation: An Experimental Study.

The physiological basis of lung protection and the impact of positive end-expiratory pressure (PEEP) during pronation in acute respiratory distress syndrome are not fully elucidated. To compare pleural pressure (Ppl) gradient, ventilation distribution, and regional compliance between dependent and nondependent lungs, and investigate the effect of PEEP during supination and pronation. We used a two-hit model of lung injury (saline lavage and high-volume ventilation) in 14 mechanically ventilated pigs and studied supine and prone positions.

Role of Positive End-Expiratory Pressure and Regional Transpulmonary Pressure in Asymmetrical Lung Injury.

Asymmetrical lung injury is a frequent clinical presentation. Regional distribution of Vt and positive end-expiratory pressure (PEEP) could result in hyperinflation of the less-injured lung. The validity of esophageal pressure (Pes) is unknown.

Human Umbilical Cord Mesenchymal Stromal Cells Attenuate Systemic Sepsis in Part by Enhancing Peritoneal Macrophage Bacterial Killing via Heme Oxygenase-1 Induction in Rats.

Background: Mesenchymal stromal cells have therapeutic potential in sepsis, but the mechanism of action is unclear. We tested the effects, dose-response, and mechanisms of action of cryopreserved, xenogeneic-free human umbilical cord mesenchymal stromal cells in a rat model of fecal peritonitis, and examined the role of heme oxygenase-1 in protection.

Methods: Separate in vivo experiments evaluated mesenchymal stromal cells in fecal sepsis, established dose response (2, 5, and 10 million cells/kg), and the role of heme oxygenase-1 in mediating human umbilical cord-derived mesenchymal stromal/stem cell effects.

Driving Pressure Is Associated with Outcome during Assisted Ventilation in Acute Respiratory Distress Syndrome.

What We Already Know About This Topic: Higher driving pressure during controlled mechanical ventilation is known to be associated with increased mortality in patients with acute respiratory distress syndrome.Whereas patients with acute respiratory distress syndrome are initially managed with controlled mechanical ventilation, as they improve, they are transitioned to assisted ventilation. Whether higher driving pressure assessed during pressure support (assisted) ventilation can be reliably assessed and whether higher driving pressure is associated with worse outcomes in patients with acute respiratory distress syndrome has not been well studied.

Overexpression of IL-10 Enhances the Efficacy of Human Umbilical-Cord-Derived Mesenchymal Stromal Cells in Pneumosepsis.

Enhancing the immunomodulatory effects of mesenchymal stromal cells (MSCs) may increase their effects in sepsis. We tested the potential for overexpression of Interleukin-10 (IL-10) in human umbilical cord (UC) MSCs to increase MSC efficacy in pneumosepsis and to enhance human macrophage function. Pneumonia was induced in rats by intratracheal instillation of ((2.

Impact of spontaneous breathing during mechanical ventilation in acute respiratory distress syndrome.

Purpose Of Review: Facilitating spontaneous breathing has been traditionally recommended during mechanical ventilation in acute respiratory distress syndrome (ARDS). However, early, short-term use of neuromuscular blockade appears to improve survival, and spontaneous effort has been shown to potentiate lung injury in animal and clinical studies. The purpose of this review is to describe the beneficial and deleterious effects of spontaneous breathing in ARDS, explain potential mechanisms for harm, and provide contemporary suggestions for clinical management.

Imaging the Injured Lung: Mechanisms of Action and Clinical Use.

Acute respiratory distress syndrome (ARDS) consists of acute hypoxemic respiratory failure characterized by massive and heterogeneously distributed loss of lung aeration caused by diffuse inflammation and edema present in interstitial and alveolar spaces. It is defined by consensus criteria, which include diffuse infiltrates on chest imaging-either plain radiography or computed tomography. This review will summarize how imaging sciences can inform modern respiratory management of ARDS and continue to increase the understanding of the acutely injured lung.

Impact of Altered Airway Pressure on Intracranial Pressure, Perfusion, and Oxygenation: A Narrative Review.

Objectives: A narrative review of the pathophysiology linking altered airway pressure and intracranial pressure and cerebral oxygenation.

Data Sources: Online search of PubMed and manual review of articles (laboratory and patient studies) of the altered airway pressure on intracranial pressure, cerebral perfusion, or cerebral oxygenation.

Study Selection: Randomized trials, observational and physiologic studies.

Diaphragmatic myotrauma: a mediator of prolonged ventilation and poor patient outcomes in acute respiratory failure.

Several mechanisms of diaphragm muscle injury (myotrauma) can result in ventilator-induced diaphragm dysfunction, including ventilator over-assistance, under-assistance, eccentric contractions, and end-expiratory shortening. In this Personal View, we summarise the evidence for the clinical relevance of these mechanisms, and present new data based on mediation analysis supporting the hypothesis that myotrauma due to ventilator over-assistance and under-assistance contribute, in part, to the effect of mechanical ventilation on clinical outcomes. The concept of diaphragmatic myotrauma has important implications for research and clinical practice.

Could nanotechnology make vitamin E therapeutically effective?

Vitamin E (VitE) has important antioxidant and anti-inflammatory effects and is necessary for normal physiological function. α-Tocopherol (α-T), the predominant form of VitE in human tissues, has been extensively studied. Other VitE forms, particularly γ-tocopherol (γ-T), are also potent bioactive molecules.

Abrupt Deflation after Sustained Inflation Causes Lung Injury.

Rationale: Ventilator management in acute respiratory distress syndrome usually focuses on setting parameters, but events occurring at ventilator disconnection are not well understood.

Objectives: To determine if abrupt deflation after sustained inflation causes lung injury.

Methods: Male Sprague-Dawley rats were ventilated (low Vt, 6 ml/kg) and randomized to control (n = 6; positive end-expiratory pressure [PEEP], 3 cm HO; 100 min) or intervention (n = 6; PEEP, 3-11 cm HO over 70 min; abrupt deflation to zero PEEP; ventilation for 30 min).

Continuous Negative Abdominal Pressure Reduces Ventilator-induced Lung Injury in a Porcine Model.

Background: In supine patients with acute respiratory distress syndrome, the lung typically partitions into regions of dorsal atelectasis and ventral aeration ("baby lung"). Positive airway pressure is often used to recruit atelectasis, but often overinflates ventral (already aerated) regions. A novel approach to selective recruitment of dorsal atelectasis is by "continuous negative abdominal pressure.

Continuous negative abdominal pressure: mechanism of action and comparison with prone position.

We recently reported that continuous negative abdominal pressure (CNAP) could recruit dorsal atelectasis in experimental lung injury and that oxygenation improved at different transpulmonary pressure values compared with increases in airway pressure (Yoshida T, Engelberts D, Otulakowski G, Katira BH, Post M, Ferguson ND, Brochard L, Amato MBP, Kavanagh BP. Am J Respir Crit Care Med 197: 534-537, 2018). The mechanism of recruitment with CNAP is uncertain, and its impact compared with a commonly proposed alternative approach to recruitment, prone positioning, is not known.