Biomedical subjects

Morton H Friedman

Publications and source records attributed to Morton H Friedman.

12 recordsLinked to original sources

PubMed2006

Correspondence of low mean shear and high harmonic content in the porcine iliac arteries.

BACKGROUND: Temporal variations in shear stress have been suggested to affect endothelial cell biology. To better quantify the range of dynamic shear forces that occur in vivo, the frequency content of shear variations that occur naturally over a cardiac cycle in the iliac arteries was determined. METHOD OF APPROACH: Computational fluid dynamic calculations were performed in six iliac arteries from three juvenile swine. Fourier analysis of the time-varying shear stress computed at the arterial wall was performed to determine the prevalence of shear forces occurring at higher frequencies in these arteries. RESULTS: While most of each artery experienced shear forces predominantly at the frequency of the heart rate, the frequency spectra at certain regions were dominated by shear forces at higher frequencies. Regions whose frequency spectra were dominated by higher harmonics generally experienced lower mean shear stress. The negative correlation between shear and dominant harmonic was significant (p=0.002). CONCLUSIONS: Since lesion development typically occurs in regions experiencing low time-average shear stress, this result suggests that the frequency content of the shear exposure may also be a contributing factor in lesion development. A better understanding of the vascular response to shear components of different frequencies might help rationalize the notion of "disturbed flow" as a hemodynamic entity.

Animals↗

PubMed2006

Statistical hemodynamics: a tool for evaluating the effect of fluid dynamic forces on vascular biology in vivo.

BACKGROUND: In vivo experimentation is the most realistic approach for exploring the vascular biological response to the hemodynamic stresses that are present in life. Post-mortem vascular casting has been used to define the in vivo geometry for hemodynamic simulation; however, this procedure damages or destroys the tissue and cells on which biological assays are to be performed. METHOD OF APPROACH: Two statistical approaches, regional (RSH) and linear (LSH) statistical hemodynamics, are proposed and illustrated, in which flow simulations from one series of experiments are used to define a best estimate of the hemodynamic environment in a second series. As an illustration of the technique, RSH is used to compare the gene expression profiles of regions of the proximal external iliac arteries of swine exposed to different levels of time-average shear stress. RESULTS: The results indicate that higher shears promote a more atheroprotective expression phenotype in porcine arterial endothelium. CONCLUSION: Statistical hemodynamics provides a realistic estimate of the hemodynamic stress on vascular tissue that can be correlated against biological response.

Animals↗

PubMed2005

Effect of hypercholesterolemia on transendothelial EBD-albumin permeability and lipid accumulation in porcine iliac arteries.

Hypercholesterolemia is associated with increased cardiovascular mortality and is known to promote the advancement of atherosclerotic lesions in experimental animal models. Juvenile swine were fed a normal or high-cholesterol diet, and the transendothelial macromolecular permeability of the external iliac arteries of these animals was assessed by measuring the uptake rate of circulating Evans blue dye (EBD). The extent and patterns of lipid-containing lesions were also determined using en face staining with Oil Red O (ORO). Sites of ORO staining often excluded EBD, possibly via the fragmentation of the internal elastic lamina, to which EBD binds. By spatially averaging the EBD uptake in arterial segments relatively free of ORO-positive lesions, it was found that endothelial permeability to albumin was greater in hypercholesterolemic pigs than in those on a normal diet (p=0.056).

Albumins↗

PubMed2005

Interaction of wall shear stress magnitude and gradient in the prediction of arterial macromolecular permeability.

Large spatial shear stress gradients have anecdotally been associated with early atherosclerotic lesion susceptibility in vivo and have been proposed as promoters of endothelial cell dysfunction in vitro. Here, experiments are presented in which several measures of the fluid dynamic shear stress, including its gradient, at the walls of in vivo porcine iliac arteries, are correlated against the transendothelial macromolecular permeability of the vessels. The fluid dynamic measurements are based on postmortem vascular casts, and permeability is measured from Evans blue dye (EBD) uptake. Time-averaged wall shear stress (WSS), as well as a new parameter termed maximum gradient stress (MGS) that describes the spatial shear stress gradient due to flow acceleration at a given point, are mapped for each artery and compared on a point-by-point basis to the corresponding EBD patterns. While there was no apparent relation between MGS and EBD uptake, a composite parameter, WSS(-0.11) MGS(0.044), was highly correlated with permeability. Notwithstanding the small exponents, the parameter varied widely within the region of interest. The results suggest that sites exposed to low wall shear stresses are more likely to exhibit elevated permeability, and that this increase is exacerbated in the presence of large spatial shear stress gradients.

Animals↗

PubMed2005

Blood flow in major blood vessels-modeling and experiments.

Although primarily motivated by an interest in atherosclerosis, modeling of arterial blood flow is also important to an understanding of congenital effects and to improvements in therapeutics. A variety of methods are available to estimate the flow field in living arteries, each with its own advantages and limitations. Tradeoffs must be made among the realism of the technique, spatial resolution, geometric fidelity, and the reliability of assumed wall mechanical properties. Once the velocity field is obtained, each differentiation, to obtain wall shear or its spatial or temporal derivatives, adds additional uncertainty into the results, demanding cautious interpretation. A distinction is made between "macro" and "micro" levels of flow structure detail: macro level structure is relatively coarse and more descriptive of the flow field, pressure, and shear distribution than the cellular response; the micro approach tries to relate a more local hemodynamic description to vascular pathology. The applications of each, and the interactions between them, are described. Issues related to these approaches, including the use of clinical data, animal experimentation, the role of cell and organ culture, and in vivo flow measurement, are briefly discussed. The summary closes with a list of recommendations for future developments in this area.

Animals↗

PubMed2004

Spatial comparison between wall shear stress measures and porcine arterial endothelial permeability.

A better understanding of how hemodynamic factors affect the integrity and function of the vascular endothelium is necessary to appreciate more fully how atherosclerosis is initiated and promoted. A novel technique is presented to assess the relation between fluid dynamic variables and the permeability of the endothelium to macromolecules. Fully anesthetized, domestic swine were intravenously injected with the albumin marker Evans blue dye, which was allowed to circulate for 90 min. After the animals were euthanized, silicone casts were made of the abdominal aorta and its iliac branches. Pulsatile flow calculations were subsequently made in computational regions derived from the casts. The distribution of the calculated time-dependent wall shear stress in the external iliac branches was directly compared on a point-by-point basis with the spatially varying in vivo uptake of Evans blue dye in the same arteries. The results indicate that in vivo endothelial permeability to albumin decreases with increasing time-average shear stress over the normal range. Additionally, endothelial permeability increases slightly with oscillatory shear index.

Albumins↗

PubMed2004

Influence of curvature dynamics on pulsatile coronary artery flow in a realistic bifurcation model.

The coronary arteries undergo large dynamic variations during each cardiac cycle due to their position on the beating heart. The local artery curvature varies significantly. In this study the influence of dynamic curvature on coronary artery hemodynamics is analyzed numerically. A realistic model of the bifurcation of the left anterior descending coronary artery and its first diagonal branch is curved by attaching it to the surface of a sphere with time-varying radius based on experimental dynamic curvature data. The description of the blood flow uses the time-dependent, three-dimensional, incompressible Navier-Stokes equations for Newtonian fluids, where the influence of the time-dependent flow domain is taken into account employing the Arbitrary Lagrangian-Eulerian technique. The inlet velocity profiles used in the computer simulation are physiologically realistic. The results show that the skewing of the axial velocity profiles near the branching site is mainly determined by the vessel branch; the bifurcating flow generally dominates the effect of curvature. The influence of curvature increases downstream of the branch. During systole, when curvature is greatest and high curvature variations appear, their effect on the flow patterns and the wall shear stress is dominated by the flow wave. Due to the smaller curvature changes during diastole, only minor effects of curvature variation on the high and relatively constant diastolic flow occur. The results demonstrate the importance of including physiologically realistic flow in the correct phase relationship with vessel motion when simulating coronary artery hemodynamics.

Biomechanical Phenomena↗

PubMed2003

Relationship between the dynamic geometry and wall thickness of a human coronary artery.

OBJECTIVE: It is widely recognized that hemodynamic and wall mechanical forces are involved in the initiation and development of atherosclerosis. In the coronary vasculature, these forces are likely mediated by arterial dynamics and geometry. This research examines the hypothesis that coronary artery motion and geometry affect the local predisposition to disease, presumably through their influence on the stresses at and in the artery wall. METHODS AND RESULTS: The dynamics of a human right coronary artery and the variation of wall thickness along its length were characterized from biplane cineangiograms and intravascular ultrasound records, respectively. The dynamic geometry parameters were distance along the vessel, cyclic displacement, axial strain, curvature, and torsion. Multiple regression analyses using principal components show that (1) no single dynamic geometry parameter has a dominant influence on wall thickness, (2) linear combinations of such parameters predict wall thickness measures with high confidence (P<0.001; R2 between 0.17 and 0.44), and (3) both the time-average values of curvature and torsion and their excursion during the cardiac cycle are positively correlated with maximum wall thickness and cross-sectional asymmetry. CONCLUSIONS: The relationships seen here support the hypothesis that dynamic geometry plays a role in the localization of early coronary artery thickening.

Catheterization↗

PubMed2003

Comparison of coronary artery dynamics pre- and post-stenting.

Stents have dramatically improved the treatment of coronary artery disease. Since the implantation of stents changes the geometry and dynamics of the coronary artery, it is reasonable to hypothesize that some of these changes may have an important effect on the development of atherosclerosis by modulating the mechanical environment. In this paper, we presented a method to compare the geometric dynamics of the coronary artery before and after stenting using biplane angiography. Two cases are reviewed and a number of parameters are proposed to describe the longitudinal change of the vessel before and after stenting. This analysis technique has the potential to identify some aspects of stent design and procedure that might improve the success rate with this therapeutic approach.

Arteries↗

PubMed2003

Effects of cardiac motion on right coronary artery hemodynamics.

The purpose of this work was to investigate the effects of physiologically realistic cardiac-induced motion on hemodynamics in human right coronary arteries. The blood flow patterns were numerically simulated in a modeled right coronary artery (RCA) having a uniform circular cross section of 2.48 mm diam. Arterial motion was specified based on biplane cineangiograms, and incorporated physiologically realistic bending and torsion. Simulations were carried out with steady and pulsatile inflow conditions (mean ReD=233, alpha=1.82) in both fixed and moving RCA models, to evaluate the relative importance of RCA motion, flow pulsation, and the interaction between motion and flow pulsation. RCA motion with a steady inlet flow rate caused variations in wall shear stress (WSS) magnitude up to 150% of the inlet Poiseuille value. There was significant spatial variability in the magnitude of this motion-induced WSS variation. However, the time-averaged WSS distribution was similar to that predicted in a static model representing the time-averaged geometry. Furthermore, the effects of flow pulsatility dominated RCA motion-induced effects; specifically, there were only modest differences in the WSS history between simulations conducted in fixed and moving RCA models with pulsatile inflow. RCA motion has little effect on time-averaged WSS patterns. It has a larger effect on the temporal variation of WSS, but even this effect is overshadowed by the variations in WSS due to flow pulsation. The hemodynamic effects of RCA motion can, therefore, be ignored as a first approximation in modeling studies.

Arteries↗

PubMed2002

Coronary artery dynamics in vivo.

There is considerable evidence that the localization and evolution of vascular disease are mediated, at least in part, by mechanical factors. The mechanical environment of the coronary arteries, which are tethered to the beating heart, is influenced by cardiac motion; the motion of the vessels must be described quantitatively to characterize fully the mechanical forces acting on and in the vessel wall. Several techniques that have been used to characterize coronary artery dynamics from biplane cineangiograms are described and illustrated. There is considerable variability in dynamic geometric parameters from site to site along a vessel, between the right and left anterior descending arteries, and among individuals, consistent with the hypotheses that variations in stresses mediated by geometry and dynamics affect the localization of atherosclerosis and individual risk of coronary heart disease. The few frankly atherosclerotic vessels that have been examined exhibit high torsions in the neighborhood of lesions, an observation which may have etiologic or diagnostic implications.

Algorithms↗

PubMed2002

Variability of 3D arterial geometry and dynamics, and its pathologic implications.

Geometric parameters and features vary within the vasculature. Furthermore, at any given anatomic site, there are substantial variations in geometry among individuals. These variations can contribute to a corresponding variability in the hemodynamic environment and, to the extent that hemodynamics affects the atherosclerotic process, the progress of vascular disease. Measurements of the geometry and wall morphometry of post-mortem human coronary arteries demonstrate a relationship between these variables that supports the notion that geometric variations can contribute to a corresponding variability in the local rate of progression of arterial disease. The dynamic geometry of the coronary arteries also varies from site to site and among individuals, and this variability too may play a role in the epidemiology of coronary artery disease.

Arteries↗