Age-Related Changes in the Mechanical Properties of Large Arteries

Abstract

A unique feature of the stiffness of large arteries is that it is one of few biological variables that more than doubles with age. Large arteries are responsible for capacitive transformation of the pulsatile ejection of the heart to a more con-tinuous blood flow for supply of oxygen and nutrients to the body organs. Detri-mental changes in mechanical properties of the large arteries decrease this capability, increasing the work load of the heart and increasing the pulsatile nature of flow to the organs with potential for end-organ damage. This chapter outlines the components of the large artery wall that give the artery mechanical strength and elasticity, describes how the stiffness of large arteries can be assessed both in vivo and ex vivo, and draws from the literature to investigate how large artery wall mechanics change with age to impact on hemodynamic parameters. Age-related functional changes include elastin fragmentation, collagen cross-linking and reduced endothelial function. Measures of large artery mechanics include vascular impedance, pulse pressure augmentation and amplification, pulse wave velocity and quantification of endothelial function. This chapter describes each of these con-cepts, giving the mathematical derivation and functional meaning of the parameters. The change in these parameters with age is summarized using evidence from both longitudinal and cross-sectional human population studies. With a lack of thera-peutic targets currently available to halt or reverse the progression of large artery stiffness with age, current treatment methods are limited to lifestyle changes for which some evidence exists for limiting the increase in large artery stiffness. 3.1 Introduction The large arteries are capacitive vessels that regulate the pulsatile ejection of blood from the ventricle, supplying a less pulsatile and continuous blood flow to the smaller arteries and microcirculation and thus to the end organs. The aorta and large 37 arteries store approximately 50 % of the stroke volume during the systolic con-traction of the left ventricle [17]. The elastic recoil of the large arteries during diastole generates blood flow continuously throughout the cardiac cycle (Fig. 3.1). The mechanical properties of the large arteries and the vessel compliance reduce with age. Whilst this pathophysiological change is usually not detrimental to the large arteries themselves, except in the case of aneurysm, it has negative effects at the pump source (ventricles) and the supply destination (end organs). Loss of compliance of systemic large arteries increases the arterial pulse pressure and therefore the maximal load on the ejecting left ventricle [112, 114, 117]. Loss of compliance also increases the transmission of the pulse to end organs that ideally receive a non-pulsatile, continuous blood flow and this could potentially lead to end organ damage [118]. This chapter summarizes the age-related changes in large artery wall mechanics. Large arteries are defined as the low resistance, conduit arteries that are the main capacitive site in the systemic arterial vasculature. The age range investigated in this chapter is adulthood, a period of increased stiffness of the large arteries. The chapter concentrates on the systemic vasculature, although concepts apply similarly to the pulmonary vasculature. The developmental and childhood phases of large artery changes are also not addressed here. The chapter is divided into three parts to introduce and describe the age-related changes in mechanical properties of large arteries. First, there is a brief discussion of the structural and functional components of the vascular wall that give, and dynamically alter, the mechanical strength of arteries. This is followed by an introduction of the fundamentals of haemodynamics that are used to measure and describe age-related changes in large arteries. Finally, the known aging characteristics of structural and functional elements of the large arteries are described and the resultant effect on large artery haemodynamics summarized. Fig. 3.1 The windkessel model of arterial blood flow. The supply of fluid is pumped by a pulsatile source (P), the ventricle, drawing through the atrioventricular valve (V AV) and driving through the aortic valve (V A). The pulsatile pump outlet is into a capacitive chamber (C) that is able to elastically extend to accommodate additional volume (dashed line). The capacitive chamber, representing the large arteries, discharges into the resistive outlet (R), or resistance vessels. This lumped parameter schematic of the vasculature represents the transformation of a pulsatile flow source, such as the ventricles, into a continuous flow source at the resistive inlet