Prevention of Trauma/Hemorrhagic Shock-Induced Mortality, Apoptosis, Inflammation and Mitochondrial Dysfunction
Abstract
Trauma complicated by hemorrhagic shock (T/HS) on the battlefield is distinct from the civilian arena especially with regards to clinical diagnosis and resuscitation protocols. Progress towards development of new first-responder resuscitation adjuvants for polytrauma and blast injuries that will maintain tissue viability requires that an agent that demonstrates efficacy in animal models that mimic T-HS and resuscitation in the civilian setting also work in animal models of T-HS that mimic combat casualties and battlefield management. We developed a rat T-HS model in which we demonstrated: 1) 72% mortality at 48 hr, 2) hypovolemic circulatory collapse, 3) left ventricular contractile dysfunction, 4) apoptosis of cardiomyocytes, alveolar epithelial cells, hepatocytes and leukocytes, 5) organ inflammation, 6) organ-specific alterations in the apoptosis transcriptome and 7) increased susceptibility to bacterial infections. Especially notable was the finding that apoptosis and inflammation required resuscitation. Remarkably, use of IL-6 (10 ug/kg) as a resuscitation adjuvant: 1) reduced mortality 5 fold, 2) prevented hypovolemic circulatory collapse, 3) prevented ventricular contractile dysfunction, 4) prevented apoptosis of cardiomyocytes, alveolar epithelial cells, hepatocytes and leukocytes, 5) reduced organ inflammation, 6) normalized the apoptosis and inflammation transcriptome in the heart, lung and liver and 7) reduced T-HS-mediated increased susceptibility to bacterial infections.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2012
- Accession Number
- ADA612818
Entities
People
- David J Tweardy
Organizations
- Baylor College of Medicine