Dynamic Measures of Arterial Stiffness in a Rodent Model

Abstract

Cardiovascular disease is one of the leading causes of death in Canada. Arterial stiffness is an important factor in the pathogenesis of cardiovascular disease. Cardiac failure, hypertension, renal failure, and dementia have all been linked to arterial stiffness. The arterial system is designed to dampen the pulses of blood from the heart's left ventricle and distribute the blood forward as steady flow in the small vessels. The pulse-dampening ability of the arterial system is reduced with age when the elastic fibers in the arterial wall degrade and fracture. The arterial stiffening process can accelerate from deposition of minerals within the arterial wall, such as calcium, from the endothelial layer becoming compromised or from fibrosis secondary to inflammation or turbulence. Arterial stiffness can be assessed post-mortem by microscopic examination of the arterial wall. However, for use in dynamic experiments and for therapeutic intervention, several ante-mortem techniques have been developed: pulse wave velocity (PWV), pulse waveform analysis (PWA), wave separation analysis (WSA), and carotid ultrasonography. Rats are important models for cardiovascular disease, toxicology, and pharmacological studies because of their convenient size and short life cycle. However, PWA and WSA have not been shown to be valid approaches for studying arterial stiffness in rat peripheral arteries. In this thesis, dynamic in vivo methods for PWA and WSA in rat peripheral arteries were developed to provide accurate measures of arterial stiffness. Software specific to the rat vasculature, PWanalyze and WSanalyze, was developed to measure PWA and WSA parameters, respectively. A comparison of these PWA and WSA methods in rat peripheral arteries was performed by creating a range of arterial stiffnesses through acute and chronic experiments. Arterial stiffness was measured in the femoral artery by a novel PWA parameter, the minimum time derivative of blood pressure dp/dt(min), as effectively as the established parameter the maximum time derivative of blood pressure dp/dt(max). A new method of WSA in femoral arteries was developed. Backward wave amplitude measured in the aorta was shown to increase as arteries stiffened and decrease as arteries relaxed with acute vasoactive drug injections. These experiments showed that dp/dt(min) and WSA are valid approaches to use when studying arterial stiffness in rats.