University of Western Ontario - Electronic Thesis and Dissertation Repository

Degree

Doctor of Philosophy

Program

Medical Biophysics

Supervisor

Dr. Cepinskas and Dr. Sanders

Abstract

Acute limb compartment syndrome (CS), a potentially devastating complication of musculoskeletal trauma, is characterized by increased pressure within a closed osseofascial compartment, resulting in muscle-threatening and ultimately limb-threatening ischemia. Urgent fasciotomy remains the only effective treatment and a current gold-standard surgical therapy. Despite a large body of literature dedicated to understanding the pathophysiology of CS, the mechanisms of CS-induced tissue damage are rather poorly understood. The established view is that increasing compartmental pressure compromises microcirculatory perfusion, restricting oxygen and nutrient delivery to vital tissues, resulting in cellular anoxia and severe tissue necrosis. However, unlike complete ischemia, CS causes myonecrosis in the face of patent vessels.

The purpose of this thesis was to investigate the mechanisms that contribute to the pathophysiology of CS. We developed a reproducible small-animal model of CS, utilizing saline infusion into the hind limb of the rat as the means of raising (and controlling) the compartment pressure. The microcirculatory parameters (capillary perfusion, tissue injury and leukocyte behaviour) were then assessed using intravital video microscopy (IVVM). A severe acute inflammatory component was detected in CS; the role of inflammation in muscle damage in compartment syndrome is unknown. This study provides evidence of the relationship between limb compartment syndrome, systemic inflammation and remote organ dysfunction, presumably through the release of pro-inflammatory cytokines (primarily TNF-α).

The ultimate goal is to lay the groundwork for the development of rational therapeutic interventions that would, at least, extend the surgical window for fasciotomy, if not prevent the development of this condition completely.

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Orthopedics Commons

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