Abstract
Spinal cord injury chronically alters cardiac structure and function and is associated with increased odds for cardiovascular disease. Here, we investigate the cardiac consequences of spinal cord injury on the acute-to-chronic continuum, and the contribution of altered bulbospinal sympathetic control to the decline in cardiac function following spinal cord injury. By combining experimental rat models of spinal cord injury with prospective clinical studies, we demonstrate that spinal cord injury causes a rapid and sustained reduction in left ventricular contractile function that precedes structural changes. In rodents, we experimentally demonstrate that this decline in left ventricular contractile function following spinal cord injury is underpinned by interrupted bulbospinal sympathetic control. In humans, we find that activation of the sympathetic circuitry below the level of spinal cord injury causes an immediate increase in systolic function. Our findings highlight the importance for early interventions to mitigate the cardiac functional decline following spinal cord injury.
Highlights
Spinal cord injury chronically alters cardiac structure and function and is associated with increased odds for cardiovascular disease
We found that left ventricular (LV) volumes (Fig. 2b–e) and systolic velocity (S′) were lower in individuals with chronic Spinal cord injury (SCI) vs. non-injured controls
We found that early filling velocity (E′) was lower and the early diastolic filling to early myocardial relaxation (E/E′) ratio was higher in individuals with chronic SCI vs. non-injured controls, potentially implying altered diastolic function
Summary
Spinal cord injury chronically alters cardiac structure and function and is associated with increased odds for cardiovascular disease. Our group has extended these clinical findings using invasive techniques in preclinical models of SCI in which we have demonstrated reductions in LV contractility (end-systolic elastance; Ees)[7,8] and cardiomyocyte atrophy[7,9], along with an associated upregulation of proteolytic pathways in LV tissue[7] These SCI-induced alterations to cardio-autonomic function, in addition to other cardio-metabolic sequelae (e.g., alterations in physical activity[10], metabolism[11–17], hemodynamics[18,19], and arterial stiffness20) likely contribute to the increase in the incidence of acute cardiovascular events[21,22] and the odds for chronic cardiovascular disease post SCI23. While the cardiac consequences of SCI are becoming increasingly characterized[2,7–9], the underlying mechanisms responsible for inducing these changes as well as the temporal development from acute-to-chronic SCI remain unclear, which precludes researchers and clinicians from optimizing treatment strategies for patients with SCI To understand these mechanisms, we conducted a series of translational experiments across humans and rats with high-level SCI to first determine the progression of cardiac changes post SCI and validate our experimental model (Part I; Fig. 1). Our findings implicate the SCIinduced loss of bulbospinal sympathetic control as a primary player in the rapid and sustained reduction in cardiac function post SCI, and suggest that interventions that target these pathways and can be applied during the acute/sub-acute setting before structural adaptations in the LV begin to occur should be further developed to improve cardiac function post SCI
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