Cardiac contractility is a key factor in determining pulse pressure and its peripheral amplification

Abstract

Background: Arterial stiffening and peripheral wave reflections have been considered the major determinants of raised pulse pressure (PP) and isolated systolic hypertension, but the importance of cardiac contractility and ventricular ejection dynamics is also recognised.

Methods: We examined the contributions of arterial compliance and ventricular contractility to variations in aortic flow and increased central (cPP) and peripheral (pPP) pulse pressure, and PP amplification (PPa) in normotensive subjects during pharmacological modulation of physiology, in hypertensive subjects, and in silico using a cardiovascular model accounting for ventricular-aortic coupling. Reflections at the aortic root and from downstream vessels were quantified using emission and reflection coefficients, respectively.

Results: cPP was strongly associated with contractility and compliance, whereas pPP and PPa were strongly associated with contractility. Increased contractility by inotropic stimulation increased peak aortic flow (323.9 ± 52.8 vs. 389.1 ± 65.1 ml/s), and the rate of increase (3193.6 ± 793.0 vs. 4848.3 ± 450.4 ml/s²) in aortic flow, leading to larger cPP (36.1 ± 8.8 vs. 59.0 ± 10.8 mmHg), pPP (56.9 ± 13.1 vs. 93.0 ± 17.0 mmHg) and PPa (20.8 ± 4.8 vs. 34.0 ± 7.3 mmHg). Increased compliance by vasodilation decreased cPP (62.2 ± 20.2 vs. 45.2 ± 17.8 mmHg) without altering $dP/dt$, pPP or PPa. The emission coefficient changed with increasing cPP, but the reflection coefficient did not. These results agreed with in silico data obtained by independently changing contractility/compliance over the range observed in vivo.

Conclusions: Ventricular contractility plays a key role in raising and amplifying PP, by altering aortic flow wave morphology.

Keywords: aortic flow; arterial compliance; cardiac contractility; hypertension; pulse pressure.

Figure 1

In vivo data showing relationships between the systolic index of contractility ($dP/dt$, left panels) or arterial compliance (right panels) and (top) central pulse pressure (PP), (middle) peripheral PP, and (bottom) PP amplification in the normotensive cohort receiving rising dose infusions of dobutamine (DB) and noradrenaline (NA) (see text for details). Pearson correlation coefficients (R) are provided for $dP/dt$ and Spearman correlation coefficients (r_s) are given for compliance. For a better interpretation of the figure, the reader is referred to the coloured web version of this article.

Figure 2

In silico data showing relationships between the systolic index of contractility ($dP/dt$, left panels) or arterial compliance (right panels) and (top) central pulse pressure (PP), (middle) peripheral PP, and (bottom) PP amplification. Pearson correlation coefficients (R) are provided for $dP/dt$ and Spearman correlation coefficients (r_s) are given for compliance.

Figure 3

In vivo data showing variations in (A) aortic peak flow (PF), (B) rate of increase in early-systolic aortic flow (ΔQ/Δt_ES), and (C) rate of decrease in late-systolic aortic flow (ΔQ/Δt_LS) with increasing contractility (light-red line, $dP/dt$ < 489 mmHg/s; red line, 489 < $dP/dt$ < 740 mmHg/s; dark-red line, $dP/dt$ > 740 mmHg/s) and compliance (light-blue line, $C$ < 1.5 ml/mmHg; blue line, 1.5 < $C$ < 2.3 ml/mmHg; dark-blue line, $C$ > 2.3 ml/mmHg) in the normotensive cohort. All measures are shown as means ± SD. Asterisks indicate a significant difference between the first and third groups. For a better interpretation of the figure, the reader is referred to the coloured web version of this article.

Figure 4

In silico data showing aortic flow (left), aortic pressure (centre), and radial pressure (right) waveforms with increasing cardiac contractility (top) and decreasing arterial compliance (bottom) in the 45–year–old virtual subject from baseline (solid lines; dashed and dotted lines indicated variations from baseline). Increasing contractility raised the peak aortic flow (PF) (A), first systolic shoulder in central pressure (P1) (B), and peripheral systolic blood pressure (pSBP) (C). Decreasing compliance increased the peak or second shoulder in central pressure (P2) (E) and the second peak or shoulder in the peripheral systolic blood pressure (pSBP₂) (F), without affecting the peak aortic flow (D). For a better interpretation of the figure, the reader is referred to the coloured web version of this article.

Figure 5

In vivo data showing variations in (A) central pulse pressure (PP), (B) peripheral PP, and (C) PP amplification with increasing contractility (light-red, dP/dt < 489 mmHg/s; red, 489 < dP/dt < 740 mmHg/s; dark-red, dP/dt > 740 mmHg/s) and compliance (light-blue, C < 1.5 ml/mmHg; blue, 1.5 < C < 2.3 ml/mmHg; dark-blue, C > 2.3 ml/mmHg) in the normotensive cohort. All measures are shown as means ± SD. Asterisks indicate a significant difference between the first and third groups. For a better interpretation of the figure, the reader is referred to the coloured web version of this article.

Figure 6

The relationship between peak emission (${\gamma }_{peak}$, top) or reflection ($R{C}_{peak}$, bottom) coefficients and central pulse pressure (PP). Left: normotensive cohort receiving rising dose infusions of dobutamine (DB) and noradrenaline (NA). Centre: hypertensive cohort. Right: increasing cardiac contractility (red dots) or decreasing arterial compliance (blue dots) from baseline in the 45–year–old virtual subject. Pearson correlation coefficients (R) are provided. For a better interpretation of the figure, the reader is referred to the coloured web version of this article.