Effects of a stiffened arterial tree on ventricular-arterial coupling in healthy and diseased hearts

David Jegger
EPFL, 2006
Thèse EPFL

Résumé

In this thesis we study ventricular-arterial coupling in rodents under the influence of arterial stiffening and myocardial infarction (MI), combination of the two considered as a novel cardiovascular research model for diseased hearts pumping against an aged, stiffened arterial tree. The stiffened arterial tree yields isolated systolic hypertension and is obtained by administration of vitamin D and nicotine (VDN). The investigation cardiac performance and ventricular-arterial coupling using such a combined model (VDN/MI) is of particular relevance to cardiac research, as cardiac disease in elderly often takes place in presence of a atherosclerotic or stiff arterial tree.. The thesis consists of an Introduction, 4 scientific papers and a brief Conclusion. The Introduction is an overview of the epidemiology of heart failure, structure and functional changes that occur during MI and VDN, material and methods used in evaluating cardiac function invasively and non-invasively (using trans-thoracic echocardiography, TTE), methods for evaluating arterial function, and finally an overview of the interaction between the heart and vessels. Paper 1: This paper addresses the issue of the universality of the normalized time-varying elastance curve. It is demonstrated that the waveform of the normalized time-varying elastance curve (En(tn)) is qualitatively comparable between the control and MI hearts, however, when En(tn) is compared quantitatively between the two groups, statistical significance is found at the ejection phase and during diastole. These differences need to be taken into account when assessing cardiac contractility based on a generalized En(tn) in different animal models or in the human in different physiological or pathological states. Paper 2: Using trans-thoracic echo (TTE), we were able to follow serial changes of cardiac function post MI using two novel parameters, the myocardioal performance index (MPI) and its ratio to left ventricular fractional shortening (LVFS/MPI), both indices being monitor successfully and as efficiently as other classical TTE parameters. More so, LVFS/MPI visually expressed better the serial modifications in cardiac function. Both MPI and LVFS/MPI were correlated to the load-independent contractile parameter, PRSW, and to the preload parameter, LVEDP, being thus pertinent in following preload changes post MI. Finally, chamber remodeling post MI can successfully be followed due to the fact that ESV and EDV both correlate to MPI and LVFS/MPI. Paper 3: We studied hemodynamics, arterial function, cardiac function and ventricular-arterial coupling in a rat model of reduced arterial compliance. The results show that arterial stiffening after VDN treatment provokes important changes in vascular impedance and wave reflections, leading to isolated systolic hypertension and LV hypertrophy, Ventricular-arterial coupling was also altered. The effects are quantitatively similar to those of arterial stiffening with age. Paper 4: We studied changes in cardiac geometry, structure and function in response to MI in control and VDN-treated (stiffened aorta) rats. The combined VDN/MI model showed the largest compromise in cardiac structure and function and exhibited the strongest biochemical signs of heart failure as compared to all other groups. The addition of MI on top of a raised afterload, seems to have accelerated the progression of heart failure. Vascular alterations also reflected well a model of ageing and calcification. This combined pathology model of failing hearts in presence of a stiff arterial tree might be fruitful in better understanding the evolution of disease and may help improving or developing novel treatment therapies. The Conclusion chapter summarizes the findings of the thesis and brings into perspective their importance and future relevance into cardiovascular research models.

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https://infoscience.epfl.ch/record/85810?ln=fr

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David Jegger
EPFL, 2006
Thèse EPFL

Résumé

Official source

https://infoscience.epfl.ch/record/85810?ln=fr

À propos de ce résultat

Concepts associés (18)

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Publications associées (23)

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Acute and Long-Term Effects of Aortic Compliance Decrease on Central Hemodynamics: A Modeling Analysis

Vasiliki Bikia, Stamatia Zoi Pagoulatou, Georgios Rovas, Nikolaos Stergiopulos

Aortic compliance is an important determinant of cardiac afterload and a contributor to cardiovascular morbidity. In the present study, we sought to provide in silico insights into the acute as well as long-term effects of aortic compliance decrease on central hemodynamics. To that aim, we used a mathematical model of the cardiovascular system to simulate the hemodynamics (a) of a healthy young adult (baseline), (b) acutely after banding of the proximal aorta, (c) after the heart remodeled itself to match the increased afterload. The simulated pressure and flow waves were used for subsequent wave separation analysis. Aortic banding induced hypertension (SBP 106 mmHg at baseline versus 152 mmHg after banding), which was sustained after left ventricular (LV) remodeling. The main mechanism that drove hypertension was the enhancement of the forward wave, which became even more significant after LV remodeling (forward amplitude 30 mmHg at baseline versus 60 mmHg acutely after banding versus 64 mmHg after remodeling). Accordingly, the forward wave's contribution to the total pulse pressure increased throughout this process, while the reflection coefficient acutely decreased and then remained roughly constant. Finally, LV remodeling was accompanied by a decrease in augmentation index (AIx 13% acutely after banding versus -3% after remodeling) and a change of the central pressure wave phenotype from the characteristic Type A ("old") to Type C ("young") phenotype. These findings provide valuable insights into the mechanisms of hypertension and provoke us to reconsider our understanding of AIx as a solely arterial parameter.

FRONTIERS MEDIA SA2021

Chargement

Blood flow in the arterial circulation induces hemodynamic forces that play an important role in various forms of vascular diseases. Temporal variation of the wall shear stress seems to play a significant role in atherogenesis and plaque stability. Flow induced wall shear stress has been linked to growth and possibly rupture of the aneurysm wall. Hemodynamic forces are patient-specific and difficult to assess in the clinic. At present, there is no in vivo measurement technique that enables measurement of hemodynamic forces to the degree of precision needed. However, when imaging modalities used frequently in clinical routine re-create high-definition, patient geometric quantification of the blood vessel, they can be employed as a base for creating predictive hemodynamic models. Which in the case of understanding healthy vs. pathologic blood flow within the cerebral or systemic circulation, renders this an interesting approach. First, we developed a "generic 1D" distributed model of the human arterial tree including the primary systemic arteries and coupled this to a heart model. The fluid mechanics equations were solved numerically to obtain pressure and flow throughout the arterial tree. A nonlinear viscoelastic constitutive law for the arterial wall was considered while distal vessels were terminated with a three-element Windkessel model. The coronary arteries were modeled assuming a systolic flow impediment proportional to ventricular varying elastance. The model predictions were validated with noninvasive measurements of pressure and flow performed in young volunteers. Flow in the large arteries was visualized with magnetic resonance imaging, cerebral flow detected with ultrasound Doppler and blood pressure measured with applanation tonometry. Model predictions at different arterial locations compared well to measured flow and pressure waves at the same anatomical points. Thus, the generic 1D model reflected the flow and pressure measurements of the "average subject" of our volunteer population. Following the same approach as the generic 1D model, we built and validated a patient-specific model. In this case, geometric data, flow and pressure measurements were obtained for one person. The model predicted pressure and flow waveforms in good agreement with the in-vivo measurements with regards to wave shape and features. Comparison with a generic 1-D model has shown that the patient-specific model better predicted pressure and flow at specific arterial sites. Overall, the patient-specific 1-D model was able to predict pressure and flow waveforms in the main systemic circulation, whereas this was not always the case for a generic 1-D model. The inherent underestimation of energy losses of the 1-D wave propagation model, due to bifurcations, non-planarity and complex geometry, were examined. The 1-D model was compared to a rigid wall 3-D computational fluid dynamic model. Newtonian and non-Newtonian blood properties were studied and the longitudinal pressure distribution along the arteries was compared with the 1-D patient-specific model mean pressure prediction. The results indicated that pressure drop is significant only in small diameter vessels such as the precerebral and cerebral arteries. In these vessels the 1-D model in comparison to 3-D models consistently underestimated pressure drop. The complex flow patterns resulting from asymmetry and bifurcation yield shear stresses in the 3-D model that were greater than the 1-D model. A 3-D unsteady fluid structure interaction simulation in a patient-specific model was performed to simultaneously capture the flow details, given by the 3-D model, and wave propagation phenomena, provided by the 1-D model. The 3-D unsteady fluid structure interaction approach is the most computationally intense and cumbersome, but it allows physiological simulations with a high level of detail and accuracy. For instance, this approach could be relevant to obtain blood flow details in regions that are prone to atherosclerotic plaques or development of aneurysms. The 3-D fluid structure interaction simulation was performed for a patient-specific aorta. Important clinical parameters such as wall shear stress were quantified and significant differences were found in comparison to the rigid wall 3-D simulation indicating the relevance of a fluid structure interaction approach. A comparison of the fluid structure interaction to an equivalent 1-D model resulted in good reproduction of the pressure and flow waveforms. The effect of a decreased compliance of the arterial tree on hemodynamical parameters has been assessed with the use of a 1-D model. Local, proximal aorta and global stiffening of the arterial tree were modeled and led to two different mechanisms that contribute to the increase in central pulse pressure. They probably both contribute to systolic hypertension and their relative contribution depends on the topology of arterial stiffening and geometrical alterations taking place in aging or in disease. All these patient-specific models are about to being in use in a clinical environment and will be useful for providing better diagnostics and treatment planning in a near future.

EPFL2011

Chargement

Arterial in vitro remodeling

Gabriela Montorzi Thorell

Vascular remodeling is defined as any enduring change in the size and composition of an adult blood vessel, allowing adaptation or repair. The vascular remodeling response has been shown to depend on a variety of endogenous and environmental factors. Physiological remodeling is a tightly regulated process that mainly occurs in response to long-term changes in hemodynamic conditions. The adaptation to these hemodynamic changes implies the production of mediators that influence structure as well as function. A loss of regulation in the adaptive response underlies the pathogenesis of major cardiovascular diseases, including hypertension, atherosclerosis, restenosis and arterial aneurismal dilatation. Specialized enzymes called matrix metalloproteinases (MMPs) have been shown to have a predominant participation in the reorganization of the vessel structure, through the degradation of the extracellular matrix scaffold. The aim of this thesis is to gain insight in the biological and mechanical processes taking place in the vascular wall as an adaptive response to different biomechanical stimuli such as blood pressure and blood flow. This work proposes a new model for the study of vascular remodeling where physical factors acting on the arterial wall can be dissociated and analyzed, individually, in relation to the biological response. The results are presented in form of an introduction, three scientific papers and a conclusion section. The investigation has been designed around three different approaches: adaptation of a non-uniform artery to an in vitro environment, vascular adaptation to steady and pulsatile pressure and vascular adaptation to unidirectional and oscillatory flow. The adaptive response to each one of the variables chosen has been analyzed through biological and biomechanical remodeling indicators of the arterial wall. The introduction is an overview of the biological and biomechanical characteristics of arterial wall in relation to the remodeling process. The contribution of vascular smooth muscle cells and extracellular matrix to physiological and pathological arterial remodeling is discussed. Paper I assesses the relative remodeling of a non-axisymmetric artery in relation to its environment. The study considers the native circumferential asymmetry of the porcine right common carotid, which results from the non-homogenous mechanical and hemodynamic native environment. The adaptive response of the artery to an in vitro perfusion environment is analyzed. The study shows that in vitro perfusion leads, through remodeling, to a circumferentially uniform scleroprotein distribution and to a change in arterial compliance. This study emphasizes the link between structural changes, the biomechanical response and the enzymatic implication in the adaptive response. In paper II we investigate the role of continuous and cyclic stretch, produced by steady or pulsatile pressure acting on the arterial wall, on the remodeling response. The study shows that exposure to continuous and cyclic stretch differentially affects the relative scleroprotein content and leads to a change in arterial wall stiffness. The adaptive outcome is studied through an integrative approach taking into consideration the geometrical and structural adaptation, the biomechanical behavior and the enzymatic agents implicated in extracellular matrix turnover. Paper III analyzes the influence of different flow patterns on the arterial adaptive response. We investigate the differential effects of oscillatory flow, mimicking a plaque-prone hemodynamic environment, and unidirectional flow, to mimicking a physiologically protective (plaquefree) environment. The effect of these hemodynamic forces on the remodeling response are characterized through the study of endothelial and smooth muscle cell function as well as through assessment of agents influencing extracellular matrix turnover. The conclusions section presents a synthesis of the results and contribution of this thesis and proposes perspectives for future studies.

EPFL2004

Chargement

EPFL2011

Arterial in vitro remodeling

Gabriela Montorzi Thorell

EPFL2004