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Project

Cardiac function after SCI: From bench to bedside

Funder: Craig H Neilsen Foundation

Funding period
USD 576 K
Funding amount
Abstract
Individuals with spinal cord injury (SCI) are at an increased risk of cardiovascular complications and an earlier onset of cardiovascular disease (CVD) than able-bodied individuals. Adverse cardiovascular adaptations in SCI are primarily caused by the combination of disturbed autonomic cardiovascular control and physical deconditioning, which ultimately combine to drive maladaptive cardiac remodeling and an early onset of CVD. Unfortunately, we know very little about the mechanisms that underlie cardiac dysfunction, and whether exercise is able to provide sufficient physiological stimuli to elicit positive cardiac adaptation in order to improve health outcomes in these individuals. To reconcile this apparent gap in knowledge, we will adopt a multidisciplinary translational approach to answer the overarching question of how SCI affects cardiac structure and function, and what mechanisms underpin such changes. For our animal studies (project 1), we will use a rat model of SCI with complete transection at T3 (with cardiovascular autonomic dysfunctions) or T10 (no cardiovascular autonomic dysfunction) to investigate the progression of and mechanisms underlying cardiac dysfunction. In an additional two groups with T3 injury, we will also assess the effect of exercise training (hind limb cycling exercise) and detraining on cardiac structure and function. Similarly, in our clinical studies we will conduct a cross-sectional comparison of left-ventricular mechanics and cardiac structure between SCI individuals with and without autonomic sparing. We will also examine the effect of upper- and lower-limb exercise training on cardiac structure and function in individuals with chronic SCI by comparing the cardiac responses to a12 week arm-crank and body weight supported treadmill training intervention, respectively. To assess cardiac structure and function in our animal model we will combine in vivo echocardiography (clinically relevant measure) to track temporal changes in cardiac structure and function with ex vivo working heart preparations (gold-standard assessment) and histological and immunohistological analysis of the heart (mechanistic outcomes). We will also take exactly the same echocardiography measures in our human project (project 2), along with detailed assessments of left-ventricular mechanics. The use of comparable interventions and identical methods of assessment between our animal and human studies will provide a true integrative assessment of cardiac function following SCI. Such translational research by the same investigators is extremely rare: this project is a unique opportunity to gain bona fide bench-to-bedside insight into cardiac dysfunction and the effect of exercise after SCI. In this respect, the current proposal addresses the urgent need for treatments aimed at decreasing cardiovascular pathology and increasing longevity in individuals with SCI. (CHN: SCIRTS chn:wdg)
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System

Categories
  • FOR (ANZSRC)

    1102 Cardiorespiratory Medicine and Haematology

  • RCDC

    Injury (total) Accidents/Adverse Effects

  • RCDC

    Injury - Trauma - (Head and Spine)

  • RCDC

    Cardiovascular

  • RCDC

    Heart Disease

  • RCDC

    Spinal Cord Injury

  • RCDC

    Neurodegenerative

  • RCDC

    Prevention

  • HRCS HC

    Cardiovascular

  • Health Research Areas

    Clinical

  • Broad Research Areas

    Clinical Medicine and Science