Brian Hayes MSc Thesis Proposal

Title: “A novel approach to the exploration of left ventricular structure and function following spinal cord injury”

Supervisor: Dr. Christopher West (Faculty of Medicine/Kinesiology)
Committee Members: Dr. Aaron Phillips (University of Calgary), Dr. David Granville (Pathology and Laboratory Medicine)

Abstract: Spinal cord injury (SCI) is known to cause significant decrements in cardiac function. However, our current understanding of this topic is based almost exclusively on load-dependent indices of cardiac function, named so because they are dependent on both the function of the heart itself, as well as the loading conditions placed on the heart by the rest of the cardiovascular system. It is therefore not known whether the observed decrements in cardiac function are due to changes to the function of the heart itself, or to the loading conditions. Recent investigations by our lab indicate that the load-independent systolic function of the left ventricle of the heart is significantly reduced by a high thoracic (T3) SCI. However, these studies utilized a highly transient intervention which allowed for the study of cardiac function under a select few loading conditions. We therefore have been unable to assess how left ventricular compliance, the gold-standard for diastolic function, is influenced by spinal cord injury.

Furthermore, clinical findings indicate that individuals with high thoracic or cervical SCI have significantly reduced orthostatic tolerance, leading them to experience numerous bouts of hypotension every day in response to postural changes. These daily bouts of hypotension have previously been correlated with increased risk of stroke and coronary artery disease, as well as cerebrovascular remodeling and accelerated cognitive decline. However, the impact of these repeated bouts of OH on intrinsic cardiac function, as well as cardiac and cerebrovascular structure, has yet to be investigated directly.

We therefore propose to combine the implementation of daily orthostatic stress with direct, in vivo assessment of cardiac function and histological analysis of cerebrovascular and cardiac tissue to answer three primary questions: 1) How does SCI affect both the load-dependent and load-independent systolic and diastolic function of the left ventricle? 2) What is the influence of repeated acute orthostatic stress during recovery from SCI on the same functional indices? 3) How does T3 SCI, with or without repeated acute orthostatic stress during recovery, influence the physiological factors of both passive and active myocardial stiffness?