Quantification of the contribution of cardiac and arterial remodeling to hypertension.

The study aim was to quantify the individual and combined contributions of both the arterial system and the heart to systolic blood pressure in hypertension. We assessed the parameters of a heart-arterial model for normotensive control subjects and hypertensive patients with left ventricular adaptation patterns classified as normal, concentric remodeling, concentric hypertrophy, or eccentric hypertrophy. The present simulations show that vascular stiffening alone increases the pulse pressure without increasing systolic blood pressure. It is only in combination with an increased peripheral resistance that arterial stiffening leads to systolic hypertension in concentric remodeling and concentric hypertrophy. The contribution of cardiac pump function to the increase in blood pressure depends on cardiac remodeling, hypertrophy, or both. In hypertensive patients with a normal left ventricle, the heart is responsible for 55% of the increase in systolic blood pressure. In concentric remodeling, concentric hypertrophy, and eccentric hypertrophy, the cardiac contribution to the increase in systolic blood pressure is 21%, 65%, and 108%, respectively. We conclude that along with arterial changes, cardiac remodeling and hypertrophy contribute to hypertension

Intracranial Stents Being Modeled as a Porous Medium: Flow Simulation in Stented Cerebral Aneurysms

Intracranial aneurysms may be treated by flow diverters, alternatively to stents and coils combination. Numerical simulation allows the assessment of the complex nature of aneurismal flow. Endovascular devices present a rather dense and fine strut network, increasing the complexity of the meshing. We propose an alternative strategy, which is based on the modeling of the device as a porous medium. Two patient-specific aneurysm data sets were reconstructed using conventional clinical setups. The aneurysms selection was done so that intra-aneurismal flow was shear driven in one and inertia driven in the other. Stents and their porous medium analog were positioned at the aneurysm neck. Physiological flow and standard boundary conditions were applied. The comparison between both approaches was done by analyzing the velocity, vorticity, and shear rate magnitudes inside the aneurysm as well as the wall shear stress (WSS) at the aneurysm surface. Simulations without device were also computed. The average flow reduction reaches 76 and 41% for the shear and inertia driven flow models, respectively. When comparing the two approaches, results show a remarkable similarity in the flow patterns and magnitude. WSS, iso-velocity surfaces and velocity on a trans-sectional plane are in fairly good agreement. The root mean squared error on the investigated parameters reaches 20% for aneurysm velocity, 30.6% for aneurysm shear rate, and 47.4% for aneurysm vorticity. It reaches 20.6% for WSS computed on the aneurysm surface. The advantages of this approach reside in its facility to implement and in the gain in computational time. Results predicted by the porous medium approach compare well with the real stent geometry model and allow predicting the main effects of the device on intra-aneurismal flow, facilitating thus the analysi

Role of elastin anisotropy in structural strain energy functions of arterial tissue

The vascular wall exhibits nonlinear anisotropic mechanical properties. The identification of a strain energy function (SEF) is the preferred method to describe its complex nonlinear elastic properties. Earlier constituent-based SEF models, where elastin is modeled as an isotropic material, failed in describing accurately the tissue response to inflation-extension loading. We hypothesized that these shortcomings are partly due to unaccounted anisotropic properties of elastin. We performed inflation-extension tests on common carotid of rabbits before and after enzymatic degradation of elastin and applied constituent-based SEFs, with both an isotropic and an anisotropic elastin part, on the experimental data. We used transmission electron microscopy (TEM) and serial block-face scanning electron microscopy (SBFSEM) to provide direct structural evidence of the assumed anisotropy. In intact arteries, the SEF including anisotropic elastin with one family of fibers in the circumferential direction fitted better the inflation-extension data than the isotropic SEF. This was supported by TEM and SBFSEM imaging, which showed interlamellar elastin fibers in the circumferential direction. In elastin-degraded arteries, both SEFs succeeded equally well in predicting anisotropic wall behavior. In elastase-treated arteries fitted with the anisotropic SEF for elastin, collagen engaged later than in intact arteries. We conclude that constituent-based models with an anisotropic elastin part characterize more accurately the mechanical properties of the arterial wall when compared to models with simply an isotropic elastin. Microstructural imaging based on electron microscopy techniques provided evidence for elastin anisotropy. Finally, the model suggests a later and less abrupt collagen engagement after elastase treatmen

Gelsolin superfamily proteins: key regulators of cellular functions

Abstract.: Cytoskeletal rearrangement occurs in a variety of cellular processes and involves a wide spectrum of proteins. Among these, the gelsolin superfamily proteins control actin organization by severing filaments, capping filament ends and nucleating actin assembly [1]. Gelsolin is the founding member of this family, which now contains at least another six members: villin, adseverin, capG, advillin, supervillin and flightless I. In addition to their respective role in actin filament remodeling, these proteins have some specific and apparently non-overlapping particular roles in several cellular processes, including cell motility, control of apoptosis and regulation of phagocytosis (summarized in table 1). Evidence suggests that proteins belonging to the gelsolin superfamily may be involved in other processes, including gene expression regulation. This review will focus on some of the known functions of the gelsolin superfamily proteins, thus providing a basis for reflection on other possible and as yet incompletely understood roles for these protein

In vivo testing of a novel adjustable glaucoma drainage device.

PURPOSE: We report on the in vivo testing of a novel noninvasively adjustable glaucoma drainage device (AGDD), which features an adjustable outflow resistance, and assess the safety and efficiency of this implant. METHODS: Under general anesthesia, the AGDD was implanted on seven white New Zealand rabbits for a duration of 4 months under a scleral flap in a way analogous to the Ex-PRESS device and set in an operationally closed position. The IOP was measured on a regular basis on the operated and control eyes using a rebound tonometer. Once a month the AGDD was adjusted noninvasively from its fully closed to its fully open position and the resulting pressure drop was measured. The contralateral eye was not operated and served as control. After euthanization, the eyes were collected for histology evaluation. RESULTS: The mean preoperative IOP was 11.1 ± 2.4 mm Hg. The IOP was significantly lower for the operated eye (6.8 ± 2 mm Hg) compared to the nonoperated eye (13.1 ± 1.6 mm Hg) during the first 8 days after surgery. When opening the AGDD from its fully closed to fully open position, the IOP dropped significantly from 11.2 ± 2.9 to 4.8 ± 0.9 mm Hg (P < 0.05). CONCLUSIONS: Implanting the AGDD is a safe and uncomplicated surgical procedure. The fluidic resistance was noninvasively adjustable during the postoperative period with the AGDD between its fully closed and fully open positions

Adaptation of Conduit Artery Vascular Smooth Muscle Tone to Induced Hypertension

We studied the changes in vascular smooth muscle (VSM) cell tone during the adaptation of rat common carotids to induced hypertension. Hypertension was induced in 8 week old male Wistar rats by total ligation of the aorta between the two kidneys. Mean blood pressure increased abruptly from 92±2 mm Hg (mean±SE) to 145±4 mm Hg and remained constant thereafter. Rats were sacrificed 2, 4, 8, and 56 days after surgery and the left common carotid artery was excised for analysis. Pressure-diameter curves were measured in vitro under normal, maximally contracted, and totally relaxed VSM. The VSM tone was analyzed in terms of its basal tone (active stress at low strains) and its myogenic tone (increase in active stress at high strains). Our results show that the capacity of the VSM to develop maximal active stress is not altered in hypertension. Basal tone, however, increases rapidly in the acute hypertension phase (2-8 days postsurgery) and drops to nearly control values at 56 days postsurgery. Also, the onset of myogenic response decreases to lower strains following the step change in pressure, to be restored back to control levels at 56 days postsurgery. We conclude that VSM adaptation is most significant in the acute hypertension phase and acts as a first, rapid defense mechanism for the arterial wall. The VSM tone returns back to normal levels once the slower geometrical and structural remodeling is developed sufficiently to restore the biomechanical environment and function of the arterial wall to control levels. © 2002 Biomedical Engineering Society. PAC2002: 8719Rr, 8719Ff, 8719U

Intracranial Stents Being Modeled as a Porous Medium: Flow Simulation in Stented Cerebral Aneurysms

Intracranial aneurysms may be treated by flow diverters, alternatively to stents and coils combination. Numerical simulation allows the assessment of the complex nature of aneurismal flow. Endovascular devices present a rather dense and fine strut network, increasing the complexity of the meshing. We propose an alternative strategy, which is based on the modeling of the device as a porous medium. Two patient-specific aneurysm data sets were reconstructed using conventional clinical setups. The aneurysms selection was done so that intra-aneurismal flow was shear driven in one and inertia driven in the other. Stents and their porous medium analog were positioned at the aneurysm neck. Physiological flow and standard boundary conditions were applied. The comparison between both approaches was done by analyzing the velocity, vorticity, and shear rate magnitudes inside the aneurysm as well as the wall shear stress (WSS) at the aneurysm surface. Simulations without device were also computed. The average flow reduction reaches 76 and 41% for the shear and inertia driven flow models, respectively. When comparing the two approaches, results show a remarkable similarity in the flow patterns and magnitude. WSS, iso-velocity surfaces and velocity on a trans-sectional plane are in fairly good agreement. The root mean squared error on the investigated parameters reaches 20% for aneurysm velocity, 30.6% for aneurysm shear rate, and 47.4% for aneurysm vorticity. It reaches 20.6% for WSS computed on the aneurysm surface. The advantages of this approach reside in its facility to implement and in the gain in computational time. Results predicted by the porous medium approach compare well with the real stent geometry model and allow predicting the main effects of the device on intra-aneurismal flow, facilitating thus the analysis

Experimental investigation of collagen waviness and orientation in the arterial adventitia using confocal laser scanning microscopy

Mechanical properties of the adventitia are largely determined by the organization of collagen fibers. Measurements on the waviness and orientation of collagen, particularly at the zero-stress state, are necessary to relate the structural organization of collagen to the mechanical response of the adventitia. Using the fluorescence collagen marker CNA38-OG488 and confocal laser scanning microscopy, we imaged collagen fibers in the adventitia of rabbit common carotid arteries ex vivo. The arteries were cut open along their longitudinal axes to get the zero-stress state. We used semi-manual and automatic techniques to measure parameters related to the waviness and orientation of fibers. Our results showed that the straightness parameter (defined as the ratio between the distances of endpoints of a fiber to its length) was distributed with a beta distribution (mean value 0.72, variance 0.028) and did not depend on the mean angle orientation of fibers. Local angular density distributions revealed four axially symmetric families of fibers with mean directions of 0°, 90°, 43° and −43°, with respect to the axial direction of the artery, and corresponding circular standard deviations of 40°, 47°, 37° and 37°. The distribution of local orientations was shifted to the circumferential direction when measured in arteries at the zero-load state (intact), as compared to arteries at the zero-stress state (cut-open). Information on collagen fiber waviness and orientation, such as obtained in this study, could be used to develop structural models of the adventitia, providing better means for analyzing and understanding the mechanical properties of vascular wal

Phase shifts of synchronized oscillators and the systolic/diastolic blood pressure relation

We study the phase-synchronization properties of systolic and diastolic arterial pressure in healthy subjects. We find that delays in the oscillatory components of the time series depend on the frequency bands that are considered, in particular we find a change of sign in the phase shift going from the Very Low Frequency band to the High Frequency band. This behavior should reflect a collective behavior of a system of nonlinear interacting elementary oscillators. We prove that some models describing such systems, e.g. the Winfree and the Kuramoto models offer a clue to this phenomenon. For these theoretical models there is a linear relationship between phase shifts and the difference of natural frequencies of oscillators and a change of sign in the phase shift naturally emerges.Comment: 8 figures, 9 page