| Description |
The overall objective of this dissertation was to provide greater insight into changes in vascular function, blood flow regulation, and exercise-induced hyperemia associated with health, chronic heart failure (CHF), and heart transplantation (HTx). In the first study, we aimed to determine the central and peripheral contributions to movement-induced hyperemia in response to passive movement by comparing humans with a denervated heart (HTx) to intact controls. We observed a four-fold reduction in the transient increase in femoral blood volume entering the leg in response to passive limb movement in the HTx recipients compared to controls. These findings highlight the key role of the reflex increases in heart rate (HR) and the associated rise in cardiac output (CO) response as an important mechanism which contributes to movement-induced hyperemia in humans. The second study investigated the changes in vascular function and the role of oxidative stress from health to CHF, HTx, and beyond. Utilizing flow-mediated vasodilation (FMD) we documented reduced vasodilatory capacity in CHF patients, which was normalized in early HTx recipients, and then an eventual decline in vascular function in the HTx recipients that were the furthest time from transplantation (>14 yrs post-HTx). The acute ingestion of the antioxidant cocktail (AOC) was able to significantly increase FMD by 55% in these >14 yrs post-HTx recipients suggesting that free radicals, and the associated decrease in nitric oxide bioavailability, are largely responsible for their endothelial dysfunction. The third study sought to better characterize the role of free radicals in regulating central and peripheral hemodynamics at rest and during exercise in patients with CHF using an oral AOC and dynamic handgrip exercise. The ingestion of the AOC had significant systemic hemodynamic effects which were only evident in the patients with CHF. Specifically, the AOC further reduced the patients already lower MAP (~5%), increased CO (~10%), and caused a fall in systemic vascular resistance (~12%). These data imply that systemic vascular resistance appears, at least in part, to be free radically-mediated. Collectively, this research has provided significant insight into the cardiovascular consequences of CHF and HTx in terms of oxidative stress, vascular function and hemodynamic regulation. |
