A Novel Large Animal Model of ARDS induced by Mitochondrial
Products Pablo Sanchez, MD PhD AATS 2015 Seattle
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No Disclosures
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-Morbidity and Mortality modest decline -Treatment remains
primarily supportive -Pharmacologic therapies not effectively
translated -Need for animal models to test new hypotheses Acute
Respiratory Distress Syndrome
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ARDS: Pathogenesis -Dysregulated Inflammation *Activation
Innate Immune System Pathogens PAMPs Cell injury molecules DAMPs
*Uncontrolled Activation of Coagulation -Alveolar Barrier
Disruption * Altered alveolar and endothelial permeability
NATURE March 2010 Am J Respir Crit Care Med Jan 2013 Rat lung:
sham Rat lung : MTD Mice lung: sham Mice lung : Histones
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Hypothesis Injection of Mitochondrial Products in swine
activates the innate immune system resulting in SIRS and ARDS. This
response is clinically similar to models of infectious sepsis.
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Methods 35-45 Kg Male Yorkshire Isolated Mitochondria Disrupted
by sonication 35-45 Kg Male Yorkshire
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Control Groupn=3 LPS Groupn=3 50ng/kg mt-DAMPsn=6 15 g/ ml of
blood volume Animals received supportive treatment according to
Surviving Sepsis Guidelines Methods