Modeling essential hypertension with a closed-loop mathematical model for the entire human circulation.

Arterial hypertension, defined as an increase in systemic arterial pressure, is a major risk factor for the development of diseases affecting the cardiovascular system. Every year, 9.4 million deaths worldwide are caused by complications arising from hypertension. Despite well-established approaches to diagnosis and treatment, fewer than half of all hypertensive patients have adequately controlled blood pressure. In this scenario, computational models of hypertension can be a practical approach for better quantifying the role played by different components of the cardiovascular system in the determination of this condition. In the present work we adopt a global closed-loop multi-scale mathematical model for the entire human circulation to reproduce a hypertensive scenario. In particular, we modify the model to reproduce alterations in the cardiovascular system that are cause and/or consequence of the hypertensive state. The adaptation does not only affect large systemic arteries and the heart but also the microcirculation, the pulmonary circulation and the venous system. Model outputs for the hypertensive scenario are validated through assessment of computational results against current knowledge on the impact of hypertension on the cardiovascular system.

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

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.

The effect of cardiac properties on arterial pulse waves: An in-silico study.

This study investigated the effects of cardiac properties variability on arterial pulse wave morphology using blood flow modelling and pulse wave analysis. A lumped-parameter model of the left part of the heart was coupled to a one-dimensional model of the arterial network and validated using reference pulse waveforms in turn verified by comparison with in vivo measurements. A sensitivity analysis was performed to assess the effects of variations in cardiac parameters on central and peripheral pulse waveforms. Results showed that left ventricle contractility, stroke volume, cardiac cycle duration, and heart valves impairment are determinants of central waveforms morphology, pulse pressure and its amplification. Contractility of the left atrium has negligible effects on arterial pulse waves. Results also suggested that it might be possible to infer left ventricular dysfunction by analysing the timing of the dicrotic notch and cardiac function by analysing PPG signals. This study has identified cardiac properties that may be extracted from in vivo central and peripheral pulse waves to assess cardiac function.

Computational hemodynamics in arteries with the one-dimensional augmented fluid-structure interaction system: viscoelastic parameters estimation and comparison with in-vivo data.

Mathematical models are widely recognized as a valuable tool for cardiovascular diagnosis and the study of circulatory diseases, especially to obtain data that require otherwise invasive measurements. To correctly simulate body hemodynamics, the viscoelastic properties of vessels walls are a key aspect to be taken into account as they play an essential role in cardiovascular behavior. The present work aims to apply the augmented fluid-structure interaction system of blood flow to real case studies to assess the validity of the model as a valuable resource to improve cardiovascular diagnostics and the treatment of pathologies. Main contributions of the paper include the evaluation of viscoelastic tube laws, estimation of viscoelastic parameters and comparison of models with literature results and in-vivo experiments. The ability of the model to correctly simulate pulse waveforms in single arterial segments is verified using literature benchmark test cases, designed taking into account a simple elastic behavior of the wall in the upper thoracic aorta and in the common carotid artery. Furthermore, in-vivo pressure waveforms, extracted from tonometric measurements performed on four human common carotid arteries and two common femoral arteries, are compared to numerical solutions. It is highlighted that the viscoelastic damping effect of arterial walls is required to avoid an overestimation of pressure peaks. Finally, an effective procedure to estimate the viscoelastic parameters of the model is herein proposed, which returns hysteresis curves of the common carotid arteries dissipating energy fractions in line with values calculated from literature hysteresis loops in the same vessel.

Hydrodynamic instability of multiple four-wave mixing.

In the regime of normal dispersion and low-frequency detunings (or high powers), four-wave mixing is shown to undergo a hydrodynamic type of instability. Such instability involves the formation of shocks (steep fronts) from smooth initial data that are regularized through the appearance of trains of fast oscillations, which exhibit solitonlike behavior, colliding elastically.