Augmentation Pressure Is Influenced by Ventricular Contractility/Relaxation Dynamics

Abstract

A ortic or central pulse pressure (cPP) determines the pulsatile load on the left ventricle, coronary, and carotid arteries and is a major risk factor for adverse cardiovascular events, with at least as strong a relation to such events as peripheral pulse pressure.1-3 cPP is widely assumed to be determined by the interaction of an outgoing forward pressure wave (FPW) generated by ventricular contraction and a backward going pressure wave (BPW) generated by reflections from the periphery of the circulation. 4,5 These components of cPP are separated by the first systolic shoulder of the aortic pulse ( Figure 1). The height of this above diastolic blood pressure (P1) is attributed to the FPW and the height above P1, the augmentation pressure (AP), to the BPW. 6 Augmentation index (AIx), the ratio of AP to cPP, is widely used as a measure of pressure wave reflection. This interpretation has, however, been criticized because of the poor relationship between the magnitude and timing of reflected waves with respect to AP. 7,8 Nitroglycerin (NTG) has a particularly marked action to reduce AP and hence cPP attributed to a change in timing or amplitude of pressure wave reflections. [9][10][11] However, an alternative explanation relates to an influence of nitrovasodilators on contraction-relaxation dynamics of the myocardium, effects observed in isolated myocytes and in vivo. 12,13The aim of the present study was to determine the mechanism by which AP is selectively reduced by NTG. We made simultaneous measurements of aortic pressure and flow and used wave intensity analysis to separate pressure waves into FPW and BPW components.14 Pressure waves were further categorized as compression or expansion (suction). A primary forward compression wave (FCW) arises from the push of the ventricle against the arterial tree and a systolic backward compression wave (BCW) from the push of the arterial tree against the ventricle. A late systolic forward expansion wave (FEW) arises from the braking effect of the ventricle in late systole. 15 These measurements together with cardiac output and the impedance of the arterial tree were obtained at baseline and after systemic administration of NTG. To further distinguish between effects of NTG related to an action on the myocardium and arterial tree, we examined effects of intracoronary infusion of NTG at a dose below the threshold required to produce systemic effects.Abstract-Augmentation pressure (AP), the increment in aortic pressure above its first systolic shoulder, is thought to be determined mainly by pressure wave reflection but could be influenced by ventricular ejection characteristics. We sought to determine the mechanism by which AP is selectively reduced by nitroglycerin (NTG). Simultaneous measurements of aortic pressure and flow were made at the time of cardiac catheterization in 30 subjects (11 women; age, 61±13 years [mean±SD]) to perform wave intensity analysis and calculate forward and backward components of AP generated by the ventricle and arterial tree, respectively. ...

Indexes of Aortic Pressure Augmentation Markedly Underestimate the Contribution of Reflected Waves Toward Variations in Aortic Pressure and Left Ventricular Mass

“…24-26 However, it is now recognized that Pa may be confounded by considerable overlap between forward and backward waves and that there is a poor relationship between the magnitude of the reflected wave and Pa. [13][14][15][16][17][18] Indeed, Pa may be determined in large part by Pf. 16 Nevertheless, studies which have used approaches to separate Pb from Pf, suggest that Pb contributes little to age-related increases in PPc.…”

“…16 Nevertheless, studies which have used approaches to separate Pb from Pf, suggest that Pb contributes little to age-related increases in PPc. 22,27 These studies were nonetheless conducted either in a sample where BP values were largely well-controlled 22 or in a sample with a narrow age range.…”

“…[13][14][15][16][17][18] However, the extent to which reflected waves derived from wave separation analysis are more strongly related to PPc and end-organ damage than indexes of aortic systolic pressure augmentation is unclear. In this study conducted in a community sample with a high prevalence of uncontrolled hypertension, we show that reflected waves are more closely associated with PPc and LVMI than forward waves, but that indexes of aortic systolic pressure augmentation markedly underestimate these effects.…”

“…However, more recently the use of Pa or AIx as indexes of wave reflection in risk prediction has been challenged. [13][14][15][16][17][18] Marked overlap between aortic forward and reflected waves may confound Pa and AIx 14,[16][17][18] and hence these measures may be poor indexes of wave reflection. Indeed, there is a weak relationship between the magnitude of the reflected wave and Pa or AIx with increases in aortic reservoir function, the timing or magnitude of the forward (Pf) or incident (Pi) wave pressures, and left ventricular systolic function playing a more important role than wave reflection in contributing to variations in Pa and AIx.…”

“…Indeed, there is a weak relationship between the magnitude of the reflected wave and Pa or AIx with increases in aortic reservoir function, the timing or magnitude of the forward (Pf) or incident (Pi) wave pressures, and left ventricular systolic function playing a more important role than wave reflection in contributing to variations in Pa and AIx. [13][14][15][16][17][18] More recent studies have, therefore, focussed on the role of reflected waves (Pb and reflected wave index [RI]), as determined using wave separation analysis, as independent determinants of age-related increases in PPc or cardiovascular damage. [19][20][21][22] However, in these studies [19][20][21][22] the extent to which Pb or RI are more closely associated with PPc or cardiovascular damage than Pa or AIx is uncertain.…”