a novel large animal model of ards induced by mitochondrial products pablo sanchez, md phd aats 2015...
TRANSCRIPT
- Slide 1
- 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
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- Bacteria Neutrophil Activation Neutrophil Activation Evolution Mitochondria Sepsis Cell Injury TLR Molecular Products PAMPs Eukaryotic Cell Molecular Products DAMPs
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- 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
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- WBC (cells/mcL) * NS Results: Clinical Signs of SIRS * *p