Surfactant Depletion Combined with Injurious Ventilation Results in a Reproducible Model of the Acute Respiratory Distress Syndrome (ARDS)

Summary

A combination of surfactant washout using 0.9% saline (35 mL/kg body weight, 37 °C) and high tidal volume ventilation with low PEEP to cause moderate ventilator induced lung injury (VILI) results in experimental acute respiratory distress syndrome (ARDS). This method provides a model of lung injury with low/limited recruitability to study the effect of various ventilation strategies for extended periods.

Abstract

Various animal models exist to study the complex pathomechanisms of the acute respiratory distress syndrome (ARDS). These models include pulmo-arterial infusion of oleic acid, infusion of endotoxins or bacteria, cecal ligation and puncture, various pneumonia models, lung ischemia/reperfusion models and, of course, surfactant depletion models, among others. Surfactant depletion produces a rapid, reproducible deterioration of pulmonary gas exchange and hemodynamics and can be induced in anesthetized pigs using repeated lung lavages with 0.9% saline (35 mL/kg body weight, 37 °C). The surfactant depletion model supports investigations with standard respiratory and hemodynamic monitoring with clinically applied devices. But the model suffers from a relatively high recruitability and ventilation with high airway pressures can immediately reduce the severity of the injury by reopening atelectatic lung areas. Thus, this model is not suitable for investigations of ventilator regimes that use high airway pressures. A combination of surfactant depletion and injurious ventilation with high tidal volume/low positive end-expiratory pressure (high Tv/low PEEP) to cause ventilator induced lung injury (VILI) will reduce the recruitability of the resulting lung injury. The advantages of a timely induction and the possibility to perform experimental research in a setting comparable to an intensive care unit are preserved.

Introduction

The mortality of the acute respiratory distress syndrome (ARDS) remains high with values above 40%¹ despite intensive research since its first description by Ashbough and Petty in 1967². Naturally, the investigation of novel therapeutic approaches is limited in the clinic due to ethical concerns and the lack of standardization of the underlying pathologies, ambient conditions, and co-medications, whereas animal models enable systematic research under standardized conditions.

Thus, experimental ARDS has been induced in either large animals (e.g., pigs) or small animals (e.g., rodents) using var....

Protocol

The experiments were conducted at the Department of Experimental Medicine, Charité - University Medicine, Berlin, Germany (certified according to the EN DIN ISO 9001:2000) and were approved by the federal authorities for animal research in Berlin, Germany, prior to the experiments (G0229/18). The principles of laboratory animal care were used in all experiments and are in accordance with the guidelines of the European and German Society of Laboratory Animal Sciences.

1. Laboratory animals and animal welfare

1. Conduct all the experiments in deeply anesthetized male pigs (German Landrace × Large White) of 3-4 months ....

Results

The P_aO₂/F_IO₂-ratio decreased during surfactant washout in all animals (Figure 3). The resulting hypoxemia, hypercapnia, and atelectasis caused an increase in pulmonary artery pressure. The details of the lung lavages are already described elsewhere⁶.

The surfactant depletion was repeated until the P_aO₂/F_IO₂ ratio remained below 100 mmHg despite mechanic.......

Discussion

This article describes the induction of experimental ARDS in pigs combining surfactant depletion by repeated lung lavages and ventilation with high tidal volumes, low PEEP, and complete inflation/deflation of the lungs. This combination causes a reproducible and comparable deterioration in gas exchange and the resulting hemodynamic compromise but limits the recruitability of the lungs. Thus, this model mimics clinical ARDS with low recruitability and allows the investigation of new ventilation regimes.

Materials

Name	Company	Catalog Number	Comments
Evita Infinity V500	Dräger		intensive care ventilator
Flow through chamber thermistor	Baxter	93-505	for measuring cardiac output
Leader Cath Set	Vygon	1,15,805	arterial catheter
Mallinckrodt Tracheal Tube Cuffed	Covidien	107-80	8.0 mm ID
MultiCath3	Vygon	1,57,300	3 lumen central venous catheter, 20 cm length
Percutaneus Sheath Introducer Set	Arrow	SI-09600	introducer sheath for pulmonary artery catheter of 4-6 Fr., 10 cm length
Swan-Ganz True Size Thermodilution Catheter	Edwards	132F5	pulmonary artery catheter, 75 cm length
urinary catheter			no specific model requiered
Vasofix Braunüle 20G	B Braun	4268113B	peripheral vein catheter
Vigilance I	Edwards		monitor