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Mehdi, Ahmadian

University of British Columbia

Purpose: High-thoracic spinal cord injury (SCI) markedly impairs cardiac function. The purpose of this dissertation 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 dissertation. 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 valid metrics for gauging cardiac contractile function in small and large animal models. Chapter 3: Through four experiments conducted in rodents, we tested whether 1) high-thoracic SCI reduces sympathetic nerve activity (SNA) and cardiac function in an animal model, 2) such reduced SNA post-injury contributes to cardiac functional decline in these animals, 3) AIH can 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 several, 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 two 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 a focus on improving cardiovascular function in individuals with SCI.

Text

2023-08-21

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/85561

Kinesiology

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/