Open Collections

The effect of simulated orthostatic hypotension on cardiac function in experimental spinal cord injury

University of British Columbia

High thoracic and cervical spinal cord injuries (SCI) are detrimental to autonomic function, increasing cardiovascular disease prevalence and impairing cardiac, cerebrovascular and arterial function. Complete SCI to the third thoracic segment (T3) or higher is known to be detrimental to the structure and intrinsic function of the left ventricle (LV). In addition, injuries to T6 or higher are known to impair the cortically-derived cardiovascular response to postural change, causing episodes of low systemic blood pressure known as orthostatic hypotension (OH) up to 28 times each day. While these frequent episodes of OH following SCI are associated with impairments in cerebrovascular function and an increased risk of coronary artery disease, it is not clear whether there is a direct relationship between OH and cardiac dysfunction following SCI. The purpose of this thesis was, therefore, to examine the impact of regular bouts of OH on cardiac function following SCI. To do so, we developed a preclinical model of OH simulation using lower body negative pressure (LBNP) in a rodent model of experimental SCI. The impact of either sham injury, T3 transection alone or T3 transection with 8 weeks of daily simulated OH on cardiac structure and function was assessed in vivo using pressure-volume catheterization and echocardiography, and ex vivo via histological analysis of myocardial tissue. We found that daily simulation of OH caused an uncoupling of the ventricular-arterial interaction following SCI, indicating a decrease in the efficiency and adaptability of the cardiovascular system that was driven by decreased LV contractile function. Additionally, we found evidence of atrophy and remodeling of cardiomyocytes following SCI and an increase in myocardial collagen following OH simulation in SCI animals. Together, the findings of this thesis imply that frequent occurrence of OH following T3 SCI may accelerate the onset of cardiac dysfunction that follows SCI and subsequently increase the risk of cardiovascular disease. Future clinical investigations are needed to understand whether these differences translate to the bedside, and apply more direct measures of ventricular mechanics and arterial function to provide context to our PV data and drive the development of informed treatment protocols.

Text

2020-07-31

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/71128

Kinesiology

University of British Columbia

UBCV

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