Title: “Acute Intermittent Hypoxia: A Potential Therapeutic To Improve Cardiac Function Following Experimental Spinal Cord Injury”
Thesis Supervisor: Dr. Christopher West
Committee Members: Drs. Glen Foster and Jonathan Little
Chair: Dr. Jordan Guenette
External Examiner: Dr. Kristine Cowley
University Examiners: Drs. Ismail Laher and Matthew Ramer
Abstract:
Purpose: High-thoracic spinal cord injury (SCI) markedly impairs cardiac function. The purpose of this thesis was to explore whether acute intermittent hypoxia (AIH), one of the most promising therapies in the field of SCI, has the potential to restore cardiac function in a rodent model of high-thoracic SCI. Prior to doing so, we first tested and validated multiple single-beat metrics of cardiac contractility that would allow us to track changes in cardiac inotropic function prior to, immediately after, and following the intervention of interest (i.e., AIH) in the present thesis. Methods: Chapter 2: In a cross-species (i.e., rats, pigs, dogs) study consisting of eight experiments, we comprehensively tested whether the majority of previously reported/tested single-beat surrogates of cardiac contractility, together with two new proposed metrics, meet the assumptions required to be considered as valid metrics for gauging cardiac contractile function in small and large animal models. Chapter 3: Through 4 experiments conducted in rodents, we tested whether 1) sympathetic nerve activity (SNA) and cardiac function are reduced in an animal model of high-thoracic SCI, 2) such reduced SNA post-injury contributes to cardiac functional decline in these animals, 3) AIH is able to mitigate sympathetic hypoactivity post-injury, and 4) AIH-induced sympathetic plasticity can be translated to end-organ function and improve cardiac function post-injury in these rodents. Results and conclusions: Findings from experiments in Chapter 2 confirmed that some, but not all, single-beat metrics of contractility can be used to measure cardiac contractile function in both small and large animal models. Findings from experiments in Chapter 3 demonstrated that high-thoracic SCI impairs cardiac function due to sympathetic hypoactivity that can be reversed with a single session of AIH when animals are treated at 2 weeks post-injury. These findings advance our understanding regarding the application of AIH in the field and set the stage for examining the potential cardiovascular benefit of therapeutic AIH in future clinical trials with focus on improving cardiovascular function in individuals with SCI.