Central and Peripheral Adaptations to Exercise in Cardiovascular Disease

Heart failure (HF), directly affected by hypertension, is a leading cause of mortality in Canada, and manifests with myocardial dysfunction. Current drug therapies have merit, however their efficacy is limited as evident by the 50% five-year survival rate for HF. Therefore, non-pharmacological treatments are required to manage hypertension and prevent HF. This thesis is an investigation into the molecular effects of exercise training in models of HF. Endurance training (ET) has long been known to exert hypotensive effects and improve the quality of life of individuals afflicted with HF. Recently, high intensity interval training (HIIT) has been touted as a time efficient alternative in this patient population. However, clinical evidence on the safety and efficacy of HIIT in patients with compromised cardiac function remains scarce. This thesis demonstrated in hypertensive rats, ET increased mitochondrial content (~25%; P<0.05), shifted fibre type to a slow/oxidative phenotype (increased IIA, decreased IIX and IIB) and increased capillarization and endothelial nitric oxide synthase (eNOS) content. In contrast, HIIT did not uniformly increase mitochondrial content, was not as robust at inducing fast-to-slow fibre type transitions, and reduced capillarization and eNOS protein with increased hypoxia inducible factor 1 alpha (HIF1α). Within the heart, ET decreased fibrosis by ~40%, promoted a 20% increase in the left ventricular capillary/fibre ratio, an increase in eNOS protein, and a decrease in HIF1α. HIIT did not decrease fibrosis, increased left ventricular mass by 20%, and increased by brain natriuretic peptide 50% in the absence of concomitant angiogenesis. Altogether, the skeletal and cardiac muscle data indicated ET and HIIT had divergent effects in hypertensive rats. In addition to hypertension, congenital heart defects represent a cause of HF. Therefore, individuals with complex adult congenital heart disease embarked on 6 months of ET. All subjects increased their exercise capacity and tolerance supporting the use of ET in humans with complex cardiovascular disease. In summary, while the current thesis illustrates the beneficial effects of ET on skeletal and cardiac muscles, as well as in complex patients, there remains a critical need for additional research on the effects of HIIT in settings of compromised cardiovascular function.

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