Systolic Hypertension Mechanisms: Effect of Global and Local Proximal Aorta Stiffening on Pulse Pressure

Decrease in arterial compliance leads to an increased pulse pressure, as explained by the Windkessel effect. Pressure waveform is the sum of a forward running and a backward running or reflected pressure wave. When the arterial system stiffens, as a result of aging or disease, both the forward and reflected waves are altered and contribute to a greater or lesser degree to the increase in aortic pulse pressure. Two mechanisms have been proposed in the literature to explain systolic hypertension upon arterial stiffening. The most popular one is based on the augmentation and earlier arrival of reflected waves. The second mechanism is based on the augmentation of the forward wave, as a result of an increase of the characteristic impedance of the proximal aorta. The aim of this study is to analyze the two aforementioned mechanisms using a 1-D model of the entire systemic arterial tree. A validated 1-D model of the systemic circulation, representative of a young healthy adult was used to simulate arterial pressure and flow under control conditions and in presence of arterial stiffening. To help elucidate the differences in the two mechanisms contributing to systolic hypertension, the arterial tree was stiffened either locally with compliance being reduced only in the region of the aortic arch, or globally, with a uniform decrease in compliance in all arterial segments. The pulse pressure increased by 58% when proximal aorta was stiffened and the compliance decreased by 43%. Same pulse pressure increase was achieved when compliance of the globally stiffened arterial tree decreased by 47%. In presence of local stiffening in the aortic arch, characteristic impedance increased to 0.10mmHgs/mL vs. 0.034mmHgs/mL in control and this led to a substantial increase (91%) in the amplitude of the forward wave, which attained 42mmHg vs. 22mmHg in control. Under global stiffening, the pulse pressure of the forward wave increased by 41% and the amplitude of the reflected wave by 83%. Reflected waves arrived earlier in systole, enhancing their contribution to systolic pressure. The effects of local vs. global loss of compliance of the arterial tree have been studied with the use of a 1-D model. Local stiffening in the proximal aorta increases systolic pressure mainly through the augmentation of the forward pressure wave, whereas global stiffening augments systolic pressure principally though the increase in wave reflections. The relative contribution of the two mechanisms depends on the topology of arterial stiffening and geometrical alterations taking place in aging or in diseas

Generic and patient-specific models of the arterial tree

Recent advance in imaging modalities used frequently in clinical routine can provide description of the geometrical and hemodynamical properties of the arterial tree in great detail. The combination of such information with models of blood flow of the arterial tree can provide further information, such as details in pressure and flow waves or details in the local flow field. Such knowledge maybe be critical in understanding the development or state of arterial disease and can help clinicians perform better diagnosis or plan better treatments. In the present review, the state of the art of arterial tree models is presented, ranging from 0-D lumped models, 1-D wave propagation model to more complex 3-D fluid-structure interaction models. Our development of a generic and patient-specific model of the human arterial tree permitting to study pressure and flow waves propagation in patients is presented. The predicted pressure and flow waveforms are in good agreement with the in vivo measurements. We discuss the utility of these models in different clinical application and future development of interes

A structural constitutive model considering angular dispersion and waviness of collagen fibres of rabbit facial veins

<p>Abstract</p> <p>Background</p> <p>Structural constitutive models of vascular wall integrate information on composition and structural arrangements of tissue. In blood vessels, collagen fibres are arranged in coiled and wavy bundles and the individual collagen fibres have a deviation from their mean orientation. A complete structural constitutive model for vascular wall should incorporate both waviness and orientational distribution of fibres. We have previously developed a model, for passive properties of vascular wall, which considers the waviness of collagen fibres. However, to our knowledge there is no structural model of vascular wall which integrates both these features.</p> <p>Methods</p> <p>In this study, we have suggested a structural strain energy function that incorporates not only the waviness but also the angular dispersion of fibres. We studied the effect of parameters related to the orientational distribution on macro-mechanical behaviour of tissue during inflation-extension tests. The model was further applied on experimental data from rabbit facial veins.</p> <p>Results</p> <p>Our parametric study showed that the model is less sensitive to the orientational dispersion when fibres are mainly oriented circumferentially. The macro-mechanical response is less sensitive to changes in the mean orientation when fibres are more dispersed. The model accurately fitted the experimental data of veins, while not improving the quality of the fit compared to the model without dispersion. Our results showed that the orientational dispersion of collagen fibres could be compensated by a less abrupt and shifted to higher strain collagen engagement pattern. This should be considered when the model is fitted to experimental data and model parameters are used to study structural modifications of collagen fibre network in physiology and disease.</p> <p>Conclusions</p> <p>The presented model incorporates structural features related to waviness and orientational distribution of collagen fibres and thus offers possibilities to better understand the relation between structure and function in the vascular wall. Also, the model can be used to further study mechanically induced collagen remodelling in vascular tissue in health and disease.</p

Effects of Reduced Cyclic Stretch on Vascular Smooth Muscle Cell Function of Pig Carotids Perfused Ex Vivo

Background With advancing age arteries stiffen, reducing arterial compliance and leading to the development of systolic hypertension and to a substantial increase in pulse pressure. An augmented pulse pressure can be a predictor of the development of hypertension, which has been linked to several cardiovascular diseases including atherosclerosis, and to pathologies such as diabetes and renal dysfunction. In this study, we tested the hypothesis that reduced wall compliance induces pulse-pressure-mediated changes in arterial wall metabolism and remodeling. Methods Porcine carotid arteries were perfused for 24 h using an ex vivo arterial support system. Control arteries were exposed to a pulse shear stress (6 ± 3 dynes/cm2) combined with a pulse pressure of 80 ± 10 mm Hg, yielding a physiological cyclic stretch of 4-5%. A reduced compliance group was also studied, in which arteries were wrapped with an external band, thereby decreasing cyclic stretch to levels <1%. Results The experimentally reduced compliance caused a decreased contraction capacity induced by norepinephrine(NE), and this was associated with lower levels of α-smooth muscle cell-actin (α-SMC-actin) and desmin protein expressions. Arteries that were exposed to a reduced cyclic stretch exhibited a higher level of matrix metalloproteinase-2 (MMP-2) expression activity as well as an increase in Ki67 expression, thereby suggesting that matrix degradation and cellular proliferation had been initiated. Furthermore, the expression of plasminogen activator inhibitor-1 (PAI-1) in stiffened arteries was lower than in the control arteries. Conclusions These findings underline the importance of cyclic stretch in the maintenance of a differentiated and fully functional phenotype of vascular SMCs, as well as in the regulation of migratory properties, proliferation, and matrix turnove

Differential Effects of Reduced Cyclic Stretch and Perturbed Shear Stress Within the Arterial Wall and on Smooth Muscle Function

Background Cyclic circumferential stretch and shear stress act in concert and yet are capable of independently mediating arterial smooth muscle function, modulating the production of superoxide and stimulating arterial remodeling. Methods Porcine carotid arteries were perfused ex vivo for 72 h. Groups combining normal (5%) and reduced (1%) stretch with high shear (6 ± 3 dyn/cm2) and oscillatory shear (0.3 ± 3 dyn/cm2) stress were created, while maintaining a pulse pressure of 80 ± 10 mm Hg. Results Total superoxide production, fibronectin expression, and gelatinase activation were mediated by shear stress, but expression in the endothelial region was mediated by reduced cyclic stretch. By plotting intensity vs. radius, we saw that superoxide and gelatinase activity were in part mediated by stress distributions throughout the vascular wall, whereas fibronectin and p22-phox were much less or not at all. These findings, when coupled with our results from tissue reactive studies, suggest that the arterial remodeling process triggered in the endothelial region due to reduced stretch causes the most significant changes in arterial smooth muscle function. Conclusions We have found that the remodeling process triggered by reduced compliance in the endothelial region of large conduit arteries has a more profound detrimental effect to smooth muscle function than that brought on by perturbed shear stress. This work provides new insight by suggesting that although mechanical stimuli such as cyclic stretch and shear stress are known to augment similar markers of vascular remodeling, the location of their expression throughout the vascular wall differs greatly and this can have dramatic effects on vascular function. American Journal of Hypertension 2009; 22:1250-1257 © 2009 American Journal of Hypertension, Lt

Prediction of the Impact of Craniospinal Compliance on the Relative Timing of Arterial and Cerebrospinal Fluid Pulsations and Perivascular Fluid Flow Into the Spinal Cord

ABSTRACT Craniospinal compliance (CC) has been hypothesized to have importance in craniospinal disorders such as hydrocephalus and syringomyelia in which tissue edema occurs. In this study we assess the impact of CC on 1) the relative timing of spinal cord blood flow (SCBF) and cerebrospinal fluid (CSF) pulsations and 2) perivascular flow (PVS) into the spinal cord (SC). A previously developed coupled model of the cardiovascular and CSF system is utilized to obtain the results. The results predict that CC can significantly alter the relative timing of arterial and CSF pulsations in the spine and total perivascular flow to the SC. CC was found to have the greatest impact on relative timing and PVF in the lumbar spine and to a lesser extent in the cervical and thoracic spine. A reduction in CC resulted in increased PVF to the SC that might help to explain tissue edema present in craniospinal disorders with reduced CC

Local pulse wave velocity in the arterial tree : site matters!

Abstract Background Several so-called loop-based methods, have been proposed to estimate local pulse wave velocity (PWV). However, previous studies have demonstrated inaccuracies in local PWV-estimates due to presence of reflections, which led to the proposition of a frequency-domain correction method [1]. The aim of this study is to assess the accuracy of PWV-estimates from different loop methods throughout the human arterial tree. Methods The output data of a validated one-dimensional (1D) model of the human systemic circulation [2] was used to simulate the physiological signals needed on the estimations of local PWV methods, and this for model settings representing a young and an aged individual (stiffness increased by factor 2). Local PWV by the PU-loop, ln(D)U-loop, ln(D)P-loop, QA-loop and the frequency-domain (PWV1-5) methods, were compared against the reference value obtained from the Bramwell-Hill equation. Results Figure 1 shows the deviation (%) of loop-based estimates of PWV and PWV1-5 from the reference. The PU-loop overestimates PWV by more than 20% for most arterial sites, while the ln(D)U- and QA-loop underestimate to the same extent at these same locations. The correction method performs acceptably well in most of the young configuration. Discrepancies increase significantly in the aged model configuration for every studied method (except the ln(D)P-loop method). Conclusion The accuracy of loop-based methods is highly dependent on the location where they are applied, and results should be interpreted with great caution. Best results were obtained for the reflection- insensitive ln(D)P-loop method, but this method does not really provide an alternative for the Bramwell-Hill equation. Figure 1 Deviation of the loop-based estimates of PWV (PU-, ln(D)U-, ln(D)P- and QA-loops) and the correction method (PWV1–5) from the reference (Bramwell-Hill), for every location of the arterial tree in the young and aged configurations. Red and blue colors indicate over- and underestimation, respectively

Generic and patient-specific models of the arterial tree

Recent advance in imaging modalities used frequently in clinical routine can provide description of the geometrical and hemodynamical properties of the arterial tree in great detail. The combination of such information with models of blood flow of the arterial tree can provide further information, such as details in pressure and flow waves or details in the local flow field. Such knowledge maybe be critical in understanding the development or state of arterial disease and can help clinicians perform better diagnosis or plan better treatments. In the present review, the state of the art of arterial tree models is presented, ranging from 0-D lumped models, 1-D wave propagation model to more complex 3-D fluid-structure interaction models. Our development of a generic and patient-specific model of the human arterial tree permitting to study pressure and flow waves propagation in patients is presented. The predicted pressure and flow waveforms are in good agreement with the in vivo measurements. We discuss the utility of these models in different clinical application and future development of interest

Can we neglect the effect of the elongation of the aorta during systole when estimating aortic wall stiffness

C