Structural and functional effects on large artery stiffness: an in-vivo experimental investigation.

Abstract

Large artery stiffness is predictive of adverse cardiovascular events and all cause mortality. Artery structure and function are determinants of artery stiffness. This thesis presents a series of in-vivo experimental studies of effect of structural and functional changes on large artery stiffness. Improved analysis methods were developed for measurement of arterial stiffness indexes, Pulse Wave Velocity (PWV) and pressure wave re ection. These were applied in studies of acute in ammation, active and passive changes in systemic pressures, aortic elastic laminae defects, and aortic calcification in rats using a novel, high fidelity, dual pressure sensing technique of measuring aortic rat PWV. Findings indicated that acute in ammation does not increase large artery stiffness, and that localised effects altering arterial structure do not manifest in in-vivo changes in large artery stiffness. The functional component of stiffness was investigated using graded systemic infusion of vasoconstrictor agents (angiotensin-II, noradrenaline, and Endothelin-1 (ET-1)) in the in-vivo ovine iliac artery. There was a markedly greater dose dependency of pressure independent change in PWV (angiotensin-II) compared to direct endothelial effects (ET-1), although blocking of ET-1 receptors produced marked changes in iliac blood ow. A similar experiment in the human iliac artery found that the B-antagonist and nitric oxide (NO) donor, x Structural and functional effects on large artery stiffness nebivolol, potentially causes a decrease in regional functional stiffness. An additional study in human subjects directly measured the decrease in forearm arterial stiffness during reactive hyperaemia following different periods of ischaemia. The findings precluded the use of this method in measuring brachial artery structural stiffness with maximal smooth muscle relaxation. Increasing periods of ischaemia had a bi-phasic relationship with changes in arterial stiffness, the first phase linked to endogenous nitric oxide release. This finding is of importance in the clinical quantification of endothelial dysfunction. These findings in basic research of arterial haemodynamics provide new quantitative contributions to the in-vivo experimental investigation of the aetiology of large artery stiffness related to structure and function of endothelial and medial wall properties. This can lead to potential clinical applications and techniques for assessment of cardiovascular risk.