Comparative Evaluation of Lipopolysaccharide Administration Methods to Induce Acute Lung Injury in Murine Models: Efficacy, Consistency, and Technical Considerations.

Context: Direct preclinical lipopolysaccharide acute lung injury (ALI) models are commonly used to study acute respiratory distress syndrome. Differences in lipopolysaccharide delivery methods may impact lung injury severity and reproducibility.

Hypothesis: We hypothesized that the severity and variability of ALI outcomes in mice would differ depending on the technique of lipopolysaccharide administration.

Limiting Overdistention or Collapse When Mechanically Ventilating Injured Lungs: A Randomized Study in a Porcine Model.

It is unknown whether preventing overdistention or collapse is more important when titrating positive end-expiratory pressure (PEEP) in acute respiratory distress syndrome (ARDS). To compare PEEP targeting minimal overdistention or minimal collapse or using a compromise between collapse and overdistention in a randomized trial and to assess the impact on respiratory mechanics, gas exchange, inflammation, and hemodynamics. In a porcine model of ARDS, lung collapse and overdistention were estimated using electrical impedance tomography during a decremental PEEP titration.

A preclinical systematic review and meta-analysis assessing the effect of biological sex in lipopolysaccharide-induced acute lung injury.

It is unclear what effect biological sex has on outcomes of acute lung injury (ALI). Clinical studies are confounded by their observational design. We addressed this knowledge gap with a preclinical systematic review of ALI animal studies.

Development and characterization of a fecal-induced peritonitis model of murine sepsis: results from a multi-laboratory study and iterative modification of experimental conditions.

Background: Preclinical sepsis models have been criticized for their inability to recapitulate human sepsis and suffer from methodological shortcomings that limit external validity and reproducibility. The National Preclinical Sepsis Platform (NPSP) is a consortium of basic science researchers, veterinarians, and stakeholders in Canada undertaking standardized multi-laboratory sepsis research to increase the efficacy and efficiency of bench-to-bedside translation. In this study, we aimed to develop and characterize a 72-h fecal-induced peritonitis (FIP) model of murine sepsis conducted in two independent laboratories.

Mechanical Ventilation in ARDS With an Automatic Resuscitator.

Background: The Oxylator is an automatic resuscitator, powered only by an oxygen cylinder with no electricity required, that could be used in acute respiratory failure in situations in which standard mechanical ventilation is not available or feasible. We aimed to assess the feasibility and safety of mechanical ventilation by using this automatic resuscitator in an animal model of ARDS.

Methods: A randomized experimental study in a porcine ARDS model with 12 pigs randomized to the Oxylator group or the control group (6 per group) and ventilated for 4 h.

Prone Position Minimizes the Exacerbation of Effort-dependent Lung Injury: Exploring the Mechanism in Pigs and Evaluating Injury in Rabbits.

Background: Vigorous spontaneous effort can potentially worsen lung injury. This study hypothesized that the prone position would diminish a maldistribution of lung stress and inflation after diaphragmatic contraction and reduce spontaneous effort, resulting in less lung injury.

Methods: A severe acute respiratory distress syndrome model was established by depleting surfactant and injurious mechanical ventilation in 6 male pigs ("mechanism" protocol) and 12 male rabbits ("lung injury" protocol).

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.

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.

A Gas-Powered, Patient-Responsive Automatic Resuscitator for Use in Acute Respiratory Failure: A Bench and Experimental Study.

Background: During the COVID-19 pandemic, a need for innovative, inexpensive, and simple ventilator devices for mass use has emerged. The Oxylator (CPR Medical Devices, Markham, Ontario, Canada) is an FDA-approved, fist-size, portable ventilation device developed for out-of-hospital emergency ventilation. It has not been tested in conditions of severe lung injury or with added PEEP.

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.

Mechanical Ventilation Induces Desensitization of Lung Axl Tyrosine Kinase Receptors.

Background: Lower tidal volumes are increasingly used in acute respiratory distress syndrome, but mortality has changed little in the last 20 yr. Therefore, in addition to ventilator settings, it is important to target molecular mediators of injury. Sepsis and other inflammatory states increase circulating concentrations of Gas6, a ligand for the antiinflammatory receptor Axl, and of a soluble decoy form of Axl.

Adverse Heart-Lung Interactions in Ventilator-induced Lung Injury.

Rationale: In the original 1974 in vivo study of ventilator-induced lung injury, Webb and Tierney reported that high Vt with zero positive end-expiratory pressure caused overwhelming lung injury, subsequently shown by others to be due to lung shear stress.

Objectives: To reproduce the lung injury and edema examined in the Webb and Tierney study and to investigate the underlying mechanism thereof.

Methods: Sprague-Dawley rats weighing approximately 400 g received mechanical ventilation for 60 minutes according to the protocol of Webb and Tierney (airway pressures of 14/0, 30/0, 45/10, 45/0 cm HO).

α-Tocopherol transfer protein mediates protective hypercapnia in murine ventilator-induced lung injury.

Rationale: Hypercapnia is common in mechanically ventilated patients. Experimentally, 'therapeutic hypercapnia' can protect, but it can also cause harm, depending on the mechanism of injury. Hypercapnia suppresses multiple signalling pathways.

Mechanical ventilation induces neutrophil extracellular trap formation.

Background: Mechanical ventilation can injure the lung and induce a proinflammatory state; such ventilator-induced lung injury (VILI) is associated with neutrophil influx. Neutrophils release DNA and granular proteins as cytotoxic neutrophil extracellular traps (NETs). The authors hypothesized that NETs were produced in a VILI model and may contribute to injury.

Hypercapnia attenuates ventilator-induced lung injury via a disintegrin and metalloprotease-17.

Hypercapnic acidosis, common in mechanically ventilated patients, has been reported to exert both beneficial and harmful effects in models of lung injury. Understanding its effects at the molecular level may provide insight into mechanisms of injury and protection. The aim of this study was to establish the effects of hypercapnic acidosis on mitogen‐activated protein kinase (MAPK) activation, and determine the relevant signalling pathways.

Vasopressin improves survival compared with epinephrine in a neonatal piglet model of asphyxial cardiac arrest.

Background: Epinephrine is a component of all resuscitation algorithms. Vasopressin is a pulmonary vasodilator and systemic vasopressor. We investigated the effect of epinephrine vs.