All ETDs from UAB

Advisory Committee Chair

Joseph L Messina

Advisory Committee Members

Marcas M Bamman

Zsuzsanna Bebok

James F Collawn

Robert W Hardy

Document Type

Dissertation

Date of Award

2015

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

Polytrauma, a combination of injuries to more than one body part or organ system, is common in modern warfare and in automobile and industrial accidents. The combination of injuries can include burn, fracture, hemorrhage, trauma to the extremities, and trauma to specific organ systems. These injuries are highly survivable when occurring singly. However, when they occur in combination the prognosis is worsened. To investigate the effects of combined injuries, we have developed a new and highly reproducible model of polytrauma. This model combines burn injury with soft tissue and gastrointestinal (GI) tract trauma. Male Sprague Dawley rats were subjected to a 15-20% total body surface area scald burn, or a single puncture of the cecum with a G30 needle, or the combination of both injuries (polytrauma). Unlike many ‘double hit’ models, the injuries in our model are concurrent. Further, the single injuries are less severe that those typically used in models of burn or GI injury. This model of polytrauma resulted in numerous distinct pathologies. The most striking outcome was an increase in mortality following polytrauma versus the single injuries alone. Polytrauma resulted in a systemic proinflammatory state with various tissues/organs producing proinflammatory cytokines in a time-dependent manner. Metabolic dysfunction, including decreased body temperature, altered feeding behavior, body weight retention, and an inability to properly maintain euglycemia were observed following polytrauma. Hepatic injury and endoplasmic reticulum stress occurred following polytrauma. Insulin resistance in liver, skeletal muscle and adipose tissue was observed and demonstrates a catabolic response to polytrauma. This insulin resistance occurred in a tissue-specific and time-dependent manner. Additionally, increased mRNA levels of ubiquitin E3 ligases were observed in skeletal muscle, which suggests priming of the ubiquitin proteosomal protein degradation pathway, likely leading to muscle atrophy. It has been suggested that animal models utilizing combinatorial injuries may be needed to more accurately mimic the human response to injury. We believe our model is ideal for studying the complex sequelae of polytrauma, which differs from single injuries. Insights gained from this model may suggest better treatment options to improve patient outcomes.

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