Slide 1

A Novel Large Animal Model of ARDS induced by Mitochondrial Products Pablo Sanchez, MD PhD AATS 2015 Seattle

Slide 2

No Disclosures

Slide 3

-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

Slide 4

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

Slide 5

Bacteria Neutrophil Activation Neutrophil Activation Evolution Mitochondria Sepsis Cell Injury TLR Molecular Products PAMPs Eukaryotic Cell Molecular Products DAMPs

Slide 6

NATURE March 2010 Am J Respir Crit Care Med Jan 2013 Rat lung: sham Rat lung : MTD Mice lung: sham Mice lung : Histones

Slide 7

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.

Slide 8

Methods 35-45 Kg Male Yorkshire Isolated Mitochondria Disrupted by sonication 35-45 Kg Male Yorkshire

Slide 9

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

Slide 10

WBC (cells/mcL) * NS Results: Clinical Signs of SIRS * *p