Name: lavage-induced surfactant depletion in pigs as a model of the acute respiratory distress syndrome (ards)
Uploaded: 2016-09-07T12:30:00
Description: Watch this Scientific Journal Video about Lavage-induced Surfactant Depletion in Pigs As a Model of the Acute Respiratory Distress Syndrome ARDS at JoVE.com

All authors disclose no financial or any other conflicts of interests.
GRANTS:
This study was supported by a grant from the Deutsche Forschungsgemeinschaft to P. Pickerodt and W. Boemke (Pi795/2-2).

The experiments were conducted at the Department of Experimental Medicine, Charit&#233; - Universit&#228;tsmedizin, 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. The principles of laboratory animal care, which were used in all experiments, were in accordance with the guidelines of the European and German Society of Laboratory Animal Sciences.
1. Animal Welfare ...

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This article describes a step by step instruction to induce severe lung injury in pigs due to surfactant washout by repeated lung lavages. This specific method enables a reproducible and comparable deterioration in lung function and pulmonary vascular resistance. It is imperative to lavage the pigs until the PaO2/FIO2 ratio decreased below 100 mmHg and stays below 100 mmHg for one hr. Once, this is achieved the animals usually do not recover from the lung injury for at least 4 ...

The mortality of human acute respiratory distress syndrome (ARDS) remains high with values between 40 and 50% 1 despite more than 4 decades of intense research. Animal models of lung injury play a major role in investigating the complex pathomechanisms or novel therapeutical approaches to reduce mortality and limit long term disabilities.
Various models have been established to induce lung injury that simulates aspects of human ARDS in either large (e.g. pigs) or small animals (e.g. rodents). Methods differ strongly, including pulmonary 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 due to large tidal volumes and high peak inspiratory pressures (ventilator-induced lung injury; VILI), smoke/burn injuries or lung ischemia/reperfusion (I/R) models are often used 2. One major disadvantage of CLP models, as well as models working with endotoxins, is the underlying inflammation which hinders the analysis of biotrauma caused by lung injury alone. Furthermore, it may take hours to days to result in lung injury, as is the case for VILI in large animals.
The induction of lung injury by surfactant washout with repeated lung lavages, as it was first described by Lachmann et al. in guinea pigs 3, is a time efficient method to induce lung injury with reproducible functional and mechanical compromises, as well as changes in pulmonary vascular resistance. The adaption of this model to mechanically ventilated pigs of about 30-60 kg body weight supports basic research with clinically used mechanical ventilators, catheters and monitors, while the compromises in gas exchange and hemodynamics are highly reproducible at the same time 4. In addition, induction of lung injury by lavages does not require specific equipment that is not commonly available in respiratory laboratories designed for experiments in large animals. The model presented in this article is suitable for research demanding equipment (e.g. ventilators) that is designed for use in humans, and furthermore ensures a high reproducibility in the occurring deteriorations in lung function. Standardization of this model helps to ensure comparability between experiments and reduce the number of animals needed. The potential recruitability of atelectatic lung regions with deliberate or unknown recruitment maneuvers is a severe limitation of this specific model. In the following article we give a detailed description of the lavage model for the induction of lung injury and provide representative data to characterize the stability of the compromises in lung function.

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		<tr height="21">
			<td height="21" style="height:21px;width:313px;">Evita Infinity V500</td>
			<td style="width:103px;">Dr&#228;ger</td>
			<td style="width:152px;"></td>
			<td style="width:167px;">intensive care ventilator</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:313px;">Vigilance I&#160;</td>
			<td style="width:103px;">Edwards</td>
			<td style="width:152px;"></td>
			<td>monitor</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:313px;">Vasofix Braun&#252;le 20G</td>
			<td style="width:103px;">B Braun</td>
			<td style="width:152px;">4268113B</td>
			<td>peripheral vein catheter</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:313px;">Mallinckrodt Tracheal Tube Cuffed</td>
			<td style="width:103px;">Covidien</td>
			<td style="width:152px;">107-80</td>
			<td>&#160;8.0 mm ID</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:313px;">MultiCath3</td>
			<td style="width:103px;">Vygon</td>
			<td style="width:152px;">157,300</td>
			<td>3 lumen central venous catheter, 20 cm length</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:313px;">Leader Cath Set</td>
			<td style="width:103px;">Vygon</td>
			<td style="width:152px;">115,805</td>
			<td>arterial catheter</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Percutaneus Sheath Introducer Set</td>
			<td style="width:103px;">Arrow</td>
			<td style="width:152px;">SI-09600</td>
			<td>introducer sheath for pulmonary artery catheter of 4-6 Fr., 10 cm length</td>
		</tr>
		<tr height="41">
			<td height="41" style="height:41px;width:313px;">Swan-Ganz True Size Thermodilution Catheter</td>
			<td style="width:103px;">Edwards</td>
			<td style="width:152px;">132F5</td>
			<td>pulmonary artery catheter, 75 cm length</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:313px;">Flow through chamber thermistor</td>
			<td style="width:103px;">Baxter</td>
			<td style="width:152px;">93-505</td>
			<td>for measuring cardiac output</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:313px;">urinary catheter</td>
			<td style="width:103px;"></td>
			<td style="width:152px;"></td>
			<td>no specific model requiered</td>
		</tr>
	</tbody>
</table>

lavage-induced surfactant depletion in pigs as a model of the acute respiratory distress syndrome (ards)

Various animal models of lung injury exist to study the complex pathomechanisms of human acute respiratory distress syndrome (ARDS) and evaluate future therapies. Severe lung injury with a reproducible deterioration of pulmonary gas exchange and hemodynamics can be induced in anesthetized pigs using repeated lung lavages with warmed 0.9% saline (50 ml/kg body weight). Including standard respiratory and hemodynamic monitoring with clinically applied devices in this model allows the evaluation of novel therapeutic strategies (drugs, modern ventilators, extracorporeal membrane oxygenators, ECMO), and bridges the gap between bench and bedside. Furthermore, induction of lung injury with lung lavages does not require the injection of pathogens/endotoxins that impact on measurements of pro- and anti-inflammatory cytokines. A disadvantage of the model is the high recruitability of atelectatic lung tissue. Standardization of the model helps to avoid pitfalls, to ensure comparability between experiments, and to reduce the number of animals needed.

PaO2/FIO2-ratio decreases during lung lavages, but the exact impact of a single lavage is difficult to predict. We start to take arterial blood gas samples from the third lavage onwards to detect a decrease in PaO2/FIO2-ratio below 100 mmHg. Once a decrease in PaO2/FIO2-ratio below 100 mmHg is achieved, we require this ratio to remain below 100 mmHg for one h...

Watch this Scientific Journal Video about Lavage-induced Surfactant Depletion in Pigs As a Model of the Acute Respiratory Distress Syndrome ARDS at JoVE.com

Lavage-induced Surfactant Depletion in Pigs As a Model of the Acute Respiratory Distress Syndrome ARDS

Repeated pulmonary lavages in anesthetized pigs induce lung injury resembling major aspects of human acute respiratory distress syndrome (ARDS). For this purpose the lungs are repeatedly lavaged with 0.9% saline at 37 &#176;C. The goal of the protocol is a reproducible mitigation of gas exchange and hemodynamics for research in ARDS.

Lavage-induced Surfactant Depletion in Pigs As a Model of the Acute Respiratory Distress Syndrome (ARDS)

Various animal models of lung injury exist to study the complex pathomechanisms of human acute respiratory distress syndrome (ARDS) and evaluate future ...

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