Name: surfactant depletion combined with injurious ventilation results in a reproducible model of the acute respiratory distress syndrome (ards)
Uploaded: 2021-04-07T14:00:00
Description: Watch this Scientific Journal Video about Surfactant Depletion Combined with Injurious Ventilation Results in a Reproducible Model of the Acute Respiratory Distress Syndrome ARDS at JoVE.com

We gratefully acknowledge the excellent technical assistance of Birgit Brandt. This study was supported by a grant of the German Federal Ministry of Education and Research (FKZ 13GW0240A-D).

The experiments were conducted at the Department of Experimental Medicine, Charit&#233; - University Medicine, Berlin, Germany (certi&#64257;ed 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 ani...

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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.
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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 various methods such as pulmo-arterial infusion of oleic acid, intravenous (i.v.) infusion of bacteria and endotoxins, or cecal ligation and puncture (CLP) models causing sepsis-induced ARDS. In addition, direct lung injuries caused by burns and smoke inhalation or lung ischemia/reperfusion (I/R) are used3. One frequently used model of direct lung injury is surfactant depletion with lung lavages as first described by Lachmann et al. in guinea pigs4.
Surfactant depletion is a highly reproducible method that results rapidly in compromises in gas exchange and hemodynamics5. A major advantage is the possibility to apply surfactant depletion in large species which enable support research with clinically used mechanical ventilators, catheters, and monitors. However, a major disadvantage of the surfactant depletion model is the instant recruitment of atelectatic lung areas whenever high airway pressures or recruiting maneuvers, such as prone positioning, are applied. Thus, the model is not suitable to investigate, e.g., automated ventilation with high PEEP levels for prolonged times6. Yoshida et al. described a combination of surfactant depletion and ventilation with high inspiratory airway pressures to induce&#160;experimental ARDS7, but their model requires an elaborate maintenance of partial pressure of oxygen (PaO2) in a predefined corridor via repeated blood gas sampling and adjustment of the driving pressure according to a sliding table of inspiratory pressure and PEEP.
Overall, a model with an overly aggressive injurious ventilation or a laborious, repeated adjustment of the ventilation regime can result in structural damage of the lungs, which is too severe and results in subsequent multiple organ failure. Thus, this article provides a detailed description of an easily feasible model of surfactant depletion plus injurious ventilation with high Tv/low PEEP for induction of experimental ARDS, which supports research with clinically used ventilation parameters for prolonged periods.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Evita Infinity V500</td>
			<td>Dr&#228;ger</td>
			<td></td>
			<td>intensive care ventilator</td>
		</tr>
		<tr>
			<td>Flow through chamber thermistor</td>
			<td>Baxter</td>
			<td>93-505</td>
			<td>for measuring cardiac output</td>
		</tr>
		<tr>
			<td>Leader Cath Set</td>
			<td>Vygon</td>
			<td>1,15,805</td>
			<td>arterial catheter</td>
		</tr>
		<tr>
			<td>Mallinckrodt Tracheal Tube Cuffed</td>
			<td>Covidien</td>
			<td>107-80</td>
			<td>&#160;8.0 mm ID</td>
		</tr>
		<tr>
			<td>MultiCath3</td>
			<td>Vygon</td>
			<td>1,57,300</td>
			<td>3 lumen central venous catheter, 20 cm length</td>
		</tr>
		<tr>
			<td>Percutaneus Sheath Introducer Set</td>
			<td>Arrow</td>
			<td>SI-09600</td>
			<td>introducer sheath for pulmonary artery catheter of 4-6 Fr., 10 cm length</td>
		</tr>
		<tr>
			<td>Swan-Ganz True Size Thermodilution Catheter</td>
			<td>Edwards</td>
			<td>132F5</td>
			<td>pulmonary artery catheter, 75 cm length</td>
		</tr>
		<tr>
			<td>urinary catheter</td>
			<td></td>
			<td></td>
			<td>no specific model requiered</td>
		</tr>
		<tr>
			<td>Vasofix Braun&#252;le 20G</td>
			<td>B Braun</td>
			<td>4268113B</td>
			<td>peripheral vein catheter</td>
		</tr>
		<tr>
			<td>Vigilance I&#160;</td>
			<td>Edwards</td>
			<td></td>
			<td>monitor</td>
		</tr>
	</tbody>
</table>

surfactant depletion combined with injurious ventilation results in a reproducible model of the acute respiratory distress syndrome (ards)

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 &#176;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.

The PaO2/FIO2-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 PaO2/FIO2 ratio remained below 100 mmHg despite mechanic...

Watch this Scientific Journal Video about Surfactant Depletion Combined with Injurious Ventilation Results in a Reproducible Model of the Acute Respiratory Distress Syndrome ARDS at JoVE.com

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

A combination of surfactant washout using 0.9% saline (35 mL/kg body weight, 37 &#176;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.

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

Various animal models exist to study the complex pathomechanisms of the acute respiratory distress syndrome (ARDS). These models include pulmo-arterial ...

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