Introduction The arterial circulation is traditionally modeledin two ways neither of which alone is able to fully account for its properties. In thewell-known two element windkessel model the circulation is viewed in terms of parallelcapacitance and resistance components. The resistance term corresponds with peripheralvascular resistance and essentially, together with cardiac output, determines the level ofmean arterial pressure. The capacitance element corresponds with arterial compliance,which is predominantly contained within the aorta and contributes to the phasic propertiesof the circulation, usually determined as pulse pressure. In the classical two elementwindkessel model arterial compliance can be determined from the pressure half time of thediastolic pressure decay curve. A variation of this which does not depend on anexponential pressure decay is that of the “area” method initially formulated by Yinand colleagues. A simpler but useful method for estimating compliance is given by theratio of stroke volume to pulse pressure. Experimental studies have demonstratedreasonable correspondence between the “area” method and that using the stroke volumeto pulse pressure ratio. A major limitation of the windkessel model is that is changes inpressure and volume within the circulation are considered to occur instantaneouslythroughout and therefore the windkessel model cannot account for important properties suchas wave reflection. An alternative model system is therefore one in which the arterialtree is considered in terms of a propagated or distributive system. This allowsconsideration of factors such as wave reflection and permits frequency domain analysis,which is not possible with the windkessel model. Wave reflection will occur at points ofthe circulation where there is a change in impedance and in man, largely occurs at thebranch points of the aorta and neighbouring vessels such as the internal iliac arteries.In this presentation use will be aorta and neighbouring vessels such as the internal iliacarteries. In this presentation use will be made, therefore, of both these models whichtogether allow a reasonable interpretation of experimental and clinical findings.

Anthropometric factors Several anthropmetric factors are of major importance indetermining large artery physiology. In youth the aorta and large arteries are elasticstructures with the degree of elasticity being greatest in the proximal aorta anddiminishing with progressive distance from the heart. With advancing age there isprogressive disruption and fragmentation of the elastic lamellae. This has a consequenceof both reducing arterial compliance and increasing pulse wave velocity. The reduction incompliance reduces the buffering capacity of the circulation in response to leftventricular ejection. An increase in pulse wave velocity favours an earlier return of thereflected pressure wave leading to partial systolic coincidence of the forward andbackward travelling waves in the proximal aorta. This leads to proximal systolic pressureaugmentation and consequently increase in pulse pressure. Due to the non-linear pressurevolume characteristics of the arterial circulation an increase in mean arterial pressurewill also lead to a stiffening of the large arteries and again result in reducedcompliance and increased pulse wave velocity. Other factors leading to an earlier arrivaltime of the reflected pressure wave are those associated with a reduced distance to thesite of major reflection, most clearly seen in the relation between body height andsystolic pressure augmentation and partly accounting for gender differences. Changes inheart rate are also of importance because of the correspondence between ejection time andcycle length such that at lower heart rates there will be greater coincidence of theforward and reflected waves. A currently unresolved question is the extent to which genderdifferences are entirely attributable to differences in body habitus. The apparentdifference between males and females in change in pressure amplification with age,together with the effects of hormone replacement therapy which are discussed below, arguein favour of there being additional gender differences.
Disease states Although there are also negative studies, the majority of studieshave found that aortic stiffness increases (reduced compliance) in the presence ofatherosclerotic disease. Studies have investigated proximal and abdominal aorta as well asintegrated compliance. The effects of atherosclerosis are consistent with its widespreadnature as evidenced from pathological studies. This finding has implications not only fora role of aortic stiffness and compliance as risk markers for the presence ofatherosclerotic disease but also in the production of clinical events. Thus increasedaortic stiffness will lead to increase pulse pressure, particularly in the proximal aorta,which will increase systolic afterload and, because of the concomitant fall in diastolicpressure, will adversely affect diastolic coronary perfusion. In addition it is likelythat is the increase in pulse pressure will lead to further arterial wall damage andinitiate a vicious cycle. In contrast to the effects of atherosclerosis, it appears thatelevation in cholesterol per se does not lead to increased arterial stiffness. lndeed inthe early stages of severe hypercholesterolaemia there is evidence for a reduction inaortic stiffness. Diabetes has been found to be associated with the effects on thearterial wall which may not be surprising in view of the widespread nature of macrovascular disease evident in diabetes. As already indicated. there is an inevitablerelationship between aortic stiffness and compliance and the level of mean blood pressuredue to the non-linear pressure volume characteristics of the arterial circulation. Howeverreduction in arterial elasticity is the major determinant of the rising systolic and pulsepressure with age. Howerver the heterogeneity in this response to ageing suggests thereare other contributory factors. We are currently investigating the role of genetic factorsin contributing to this heterogeneity by relating polymorphisms of a number of candidategenes to parameters of arterial behaviour such as compliance and pulse pressure. Ininitial studies we have investigated the role for polymorphisms in the fibrillin gene (thegene involved in Marfan′s syndrome) and have indeed found a relationship with pulsepressure (in normal individuals). We are currently proceeding to establish a role forpolymorphisms in other relevant genes.
Modulation Although aortic stiffness and systemic arterial compliance are to alarge extent dependent on non-modifiable anthropometric factors, there is now substantialevidence that they are also amenable to modification by a number of interventions. Thus inrecent years research by our group and others has demonstrated that arterial compliancecan be increased by aerobic exercise training, hormone replacement therapy inpostmenopausal women, dietary supplementation with n-3 fatty acids, and dietary isoflavones. The changes induced by these various strategies are over and above thoseexpected to occur passively as a result of change in mean blood pressure. Muscle strengthtraining, however, is associated with a reduction in arterial compliance and a concomitantincrease in pulse pressure. There is also evidence for a large artery affect of specificantihypertensive medications although many of these studies are confounded by changes inmean arterial pressure and to a lesser extent heart rate. The increasing evidence thatpulse pressure is an important and independent haemodynamic predictor of futurecardiovascular events, together with the fact that pulse pressure elevation with age islargely a phenomenon due to changes in large artery structure, highlights the importanceof developing pharmacological and other therapeutic strategies to specifically modulatethe change in arterial behaviour with age. Methods of selectively affecting pulse pressurewill also allow investigations to determine the relative importance of pulse pressurereduction versus mean pressure reduction in affecting cardiovascular outcomes. Althoughthere is currently some evidence from sub group analyses of large trials to support thenotion that pulse pressure is a truly independent factor these analyses are complicatedsince most interventions also have affected mean pressure.
Coronary artery compliance In addition to studying large artery compliance ourresearch group has recently been investigating compliance of epicardial coronary arteries.These studies are conducted using intravascular ultrasound to determine coronary arterycross sectional area and a pressure tip manometer placed in the origin of the left maincoronary artery to continuously record blood pressure during the acquisition of ultrasoundimages. We are studying patients with known coronary artery disease at the time of theirrevascularisation by coronary angioplasty and ,as a comparison group, patients very earlyfollowing cardiac transplantation. Such patients are investigated within the first twoweeks and well before the appearance of any graft occlusive disease. Our first objectivein the studies is to determine whether there is indeed a relationship between systemicarterial compliance and coronary compliance, measured at sites not involvingangiographically evident stenoses, in subjects with coronary artery disease. Wehypothesised that in subjects with coronary disease such a relationship will be evident.On the other hand, we do not anticipate finding such a relationship in the cardiactransplant recipients because their coronary and systemic circulations are biologically distince. In addition to investigating the relationships between coronary and systemiccompliance we also are investigating whether the presence of widespread atheroma in thecoronary artery disease patients affects their coronary mechanics. Data obtained to datehave revealed that coronary artery compliance and distensibility are indeed less inpatients with coronary artery disease than in those investigated early following theircardiac transplantation. Our longer-term objective is to establish whether the propertiesof the “parent” coronary artery also contribute to the liability of plaques torupture. This seems plausible since it is already established that vulnerable plaques tendto fissure at the margin, that is at the border between the “at risk” plaques and theremainder of the coronary artery.
Conclusions Large and conduit artery properties have to a large extent beenignored in considering the physiology and pathophysiology of the circulation. Recentepidemiological and clinical trial data on the prognostic importance of pulse pressure,which is dependent on arterial stiffness for its origin, has focused attention on thisaspect of cardiovascular physiology. Current studies on the interaction between largearteries and coronary arteries and on the potential for modulation of large arteryproperties may open the way to the development of new therapeutic possibilities. (Anthony M Dart)