Effect of Carbon Monoxide-Releasing Molecule-3 on the Severity of Endothelial Dysfunction Due to Elevation of Hydrostatic Pressure in an In Vitro Model of Compartment Syndrome

Compartment syndrome (CS) is a surgical emergency caused by elevated pressure within a closed osseofascial compartment. It leads to microvascular dysfunction, limiting oxygen and nutrient delivery, gas exchange, resulting in cellular anoxia, muscle necrosis and cell death. Currently, the only effective treatment is surgical fasciotomy. Recently, carbon monoxide (CO) delivered via carbon monoxide releasing molecule-3 (CORM-3) has been shown to improve microvascular perfusion and convey anti-inflammatory benefits in animal models of CS. The contribution of elevated hydrostatic pressure (EHP) to the pathophysiology of CS was examined in an in vitro model of CS. We found that EHP led to increased oxidative stress, apoptosis and structural changes within the human vascular endothelial cells; application of CORM-3 diminished the magnitude of these detrimental responses. The data suggest that CORM-3 provides beneficial effects by preventing endothelial activation while preserving endothelial integrity, making CORM-3 an excellent potential adjunct pharmacological therapeutic in CS.

Name thesis:degree_name

M Sc

Discipline thesis:degree_discipline

Surgery

Grantor dc:publisher

The University of Western Ontario

Year dc:date.issued

2017

Author dc:creator

• Taylor, Michel A.

Advisor dc:contributor.advisor

• Lawendy, Abdel-Rahman

• compartment syndrome
• elevated hydrostatic pressure
• human vascular endothelial cells
• CORM-3
• oxidative stress
• apoptosis
• inflammation

Language dc:language.iso

en_ca

Handle dc:identifier.uri

https://hdl.handle.net/20.500.14721/27701

OAI identifier oai:identifier

oai:uwo.scholaris.ca:20.500.14721/27701