Mehdi Ahmadian’s PhD Thesis Proposal

Title: “Acute intermittent hypoxia: a potential therapeutic to improve cardiac function following experimental spinal cord injury”

Thesis Supervisor: Dr. Christopher West
Committee Members: Dr. Glen Foster, Dr. Johnathan Little
Chair:
Dr. Bill Sheel

Abstract: Cardiovascular complications are one of the leading causes of morbidity and mortality in individuals with spinal cord injury (SCI). Such impaired cardiovascular function post-injury is now well-documented to be due to the sympathetic nervous system dysfunction. Consequently, studies targeting this neural system to offset/mitigate cardiovascular function post-injury are urgently required. Acute intermittent hypoxia (AIH) is reported to induce plasticity within multiple neural systems post-SCI. The fact that AIH induces plasticity within multiple systems raises the exciting possibility that AIH may also cause plasticity in the sympathetic nervous system that tightly controls cardiovascular function. As such, if AIH induces plasticity in the sympathetic nerves post-SCI, then it may alleviate cardiovascular dysfunction post-SCI. Before testing the efficacy of this promising therapy, in the project 1 I attempt to validate some indirect metrics that would allow me to quantify cardiac intrinsic function over time within in the same animal and in those experiments in which assessing cardiac intrinsic function is not feasible via routine procedures. In project 2, I aim to explore how cardiac and peripheral hemodynamic function responses to acute delivery of hypoxia and whether AIH is effective in improving cardiac(vascular) function in a rodent model of high-thoracic SCI, as well as comparing those results to uninjured animals. If proven to be effective, in project 3, I aim to explore what orchestrates such AIH-induced cardiac(vascular) responses post-SCI, including direct assessment of sympathetic nerve activity.