Modeling the adaptive permeability response of porcine iliac arteries to acute changes in mural shear.

The hypothesis that much of the uptake of macromolecules by the vascular wall takes place while the endothelial lining is adapting to changes in its hemodynamic environment is being tested by a series of in vivo measurements of the uptake of Evans-blue-dye-labeled albumin by porcine iliac arteries subjected to acute changes in blood flow. The uptake data are interpreted through an ad hoc model of the dynamic permeability response that is proposed to accompany alterations in mural shear. The model is able to correlate, with a single set of parameters, the vascular response to a variety of experimental protocols, including sustained step increases and decreases in shear, and alternations in shear of various periods. The best-fit parameters of the model suggest that the adaptive response to an increase in shear proceeds with a latency of approximately 1.5 min and a time constant of approximately 90 min that is substantially shorter than the response to a decrease in shear.

Traditional engineering in the biological century: the biotraditional engineer.

The increasing importance of life science in all engineering is prompting departments in the traditional engineering disciplines to offer life science as part of their curricula. Students who take advantage of this opportunity--"biotraditional engineers"--will be well positioned for careers in their discipline and in related areas of bioengineering. The founder engineering societies, such as the Bioengineering Division of ASME, are responding to this trend by broadening their scope and working increasingly across interdisciplinary borders.

Intraoral chilling versus oral sumatriptan for acute migraine.

Migraine pathophysiology is associated with a dural inflammation. Recent evidence suggests that the primary inflammation occurs in a maxillary nerve segment, accessible intraorally. Local tenderness, related to symptom laterality, has been palpated consistently in asymptomatic migraine patients, and significant migraine relief has been obtained from chilling confined to this area. Thirty-five symptomatic episodic migraine patients were enrolled in this study, comparing 40 minutes of bilateral intraoral chilling, 50 mg of oral sumatriptan, and 40 minutes of sham (tongue) chilling. Hollow metal tubes chilled by circulating ice water were held in the maxillary molar periapical areas by the patient. Pain and nausea were recorded at baseline and 1, 2, 4, and 24 hours after start of treatment, using a numeric symptom-relief scale. Significant mean headache relief was obtained by maxillary chilling and sumatriptan at all four time intervals, with poor relief obtained by placebo. Maxillary chilling was more effective than sumatriptan at all four time intervals. Significant nausea relief was obtained by maxillary chilling and sumatriptan at posttreatment and 2 and 4 hours later. At 24 hours, some headache and nausea recurrence was noted with sumatriptan. The repeated-measures analysis of variance indicated that both treatments, drug (P = 0.024) and maxillary chilling (P = 0.001), reduced the headache, as compared with the control group. Tenderness suggests local inflammation associated with vasodilatation and edema. Because chilling can resolve local edema, these findings raise the possibility that an intraoral inflammation may be a factor in migraine etiology.

Dynamics of human coronary arterial motion and its potential role in coronary atherogenesis.

Mechanical forces have been widely recognized to play an important role in the pathogenesis of atherosclerosis. Since coronary arterial motion modulates both vessel wall mechanics and fluid dynamics, it is hypothesized that certain motion patterns might be atherogenic by generating adverse wall mechanical forces or fluid dynamic environments. To characterize the dynamics of coronary arterial motion and explore its implications in atherogenesis, a system was developed to track the motion of coronary arteries in vivo, and employed to quantify the dynamics of four right coronary arteries (RCA) and eight left anterior descending (LAD) coronary arteries. The analysis shows that: (a) The motion parameters vary among individuals, with coefficients of variation ranging from 0.25 to 0.59 for axially and temporally averaged values of the parameters; (b) the motion parameters of individual vessels vary widely along the vessel axis, with coefficients of variation as high as 2.28; (c) the LAD exhibits a greater axial variability in torsion, a measure of curve "helicity," than the RCA; (d) in comparison with the RCA, the LAD experiences less displacement (p = 0.009), but higher torsion (p = 0.03). These results suggest that: (i) the variability of certain motion parameters, particularly those that exhibit large axial variations, might be related to variations in susceptibility to atherosclerosis among different individuals and vascular regions; and (ii) differences in motion parameters between the RCA and LAD might relate to differences in their susceptibility to atherosclerosis.

The effect of celiac and renal artery outflows on near-wall velocities in the porcine iliac arteries.

The effects of the outflow of aortic blood through the celiac and renal arteries on the flow field in the external iliac arteries were studied under steady and physiologically realistic pulsatile flow conditions. Laser Doppler velocimetry (LDV) measurements were made close to the medial, lateral, ventral, and dorsal walls of the external iliac branches of a clear, flow-through replica of a porcine aorta and its daughter vessels. The outflow from each branch of the replica was controlled so that the infrarenal aortic flow rate and the flow partition at the aortic trifurcation were the same for all experiments. LDV measurements were made with flow exiting through both the renal and celiac artery ostia, only the celiac ostium, and neither ostium. The steady flow results indicate that while the outflow through the renal arteries did not have a significant effect on near wall shear rate in the external iliac arteries, the flow through the celiac artery did. However, in pulsatile flow, three indices of near wall velocity in the iliac arteries were unaffected by celiac artery outflow, while a fourth showed a small effect that can be attributed to differences in minimum velocity. These results indicate that reliable simulations of blood flow in the external iliac arteries can be carried out without including the renal and celiac vessels, provided that the correct infrarenal flow wave is used. They also demonstrate that the flow field downstream of a region, such as a branch, that strongly alters the flow, can be nearly independent of the velocity field entering the region.

Effect of periodic alterations in shear on vascular macromolecular uptake.

Experiments were carried out in swine to test the hypothesis that changes in the fluid dynamic environment of the arterial wall, with time constants of several minutes to perhaps a few hours, prompt adaptive responses that transiently increase endothelial permeability. After parenteral Evans Blue Dye (EBD) administration, the hemodynamics of the external iliac arteries of the experimental animals were altered using a reversible arteriovenous femoral shunt. For 3 h, the shunt was opened and closed with a period (tau) between 1-180 min. Subsequently, the animal was euthanized and the iliac vessels were photographed en face to obtain the distribution of EBD-bound albumin uptake by the tissue during its exposure to the dye. Albumin uptake increases with tau in a fashion that can be explained by an a priori model of the adaptive permeability response, with a time constant of about an hour.

Method for assessing the need for case-specific hemodynamics: application to the distribution of vascular permeability.

A common approach to understanding the role of hemodynamics in atherogenesis is to seek relationships between parameters of the hemodynamic environment, and the distribution of tissue variables thought to be indicative of early disease. An important question arising in such investigations is whether the distributions of tissue variables are sufficiently similar among cases to permit them to be described by an ensemble average distribution. If they are, the hemodynamic environment needs be determined only once, for a nominal representative geometry; if not, the hemodynamic environment must be obtained for each case. A method for classifying distributions from multiple cases to answer this question is proposed and applied to the distributions of the uptake of Evans blue dye labeled albumin by the external iliac arteries of swine in response to a step increase in flow. It is found that the uptake patterns in the proximal segment of the arteries, between the aortic trifurcation and the ostium of the circumflex iliac artery, show considerable case-to-case variability. In the distal segment, extending to the deep femoral ostium, many cases show very little spatial variation, and the patterns in those that do are similar among the cases. Thus the response of the distal segment may be understood with fewer simulations, but the proximal segment has more information to offer.

Quantification of 3-D coronary arterial motion using clinical biplane cineangiograms.

Speculation that the motion of the coronary arteries might be involved in the pathogenesis of coronary atherosclerosis has generated growing interest in the study of this motion. Accordingly, a system has been developed to quantify 3-D coronary arterial motion using clinical biplane cineangiograms. Exploiting the temporal continuity of sequential angiographic images, a template matching technique is designed to track the non-uniform frame-to-frame motion of coronary arteries without assuming that the vessels experience uniform axial strain. The implementation of the system is automated by a coarse-to-fine matching process, thus improving the efficiency and objectivity of motion analysis. The system has been validated and employed to characterize the in vivo motion dynamics of human coronary arteries; illustrative results show that this system is a promising tool for routine clinical and laboratory analysis of coronary arterial motion.

The craniocervical connection: a retrospective analysis of 300 whiplash patients with cervical and temporomandibular disorders.

Because the concept of whiplash as a causative factor for temporomandibular disorders (TMD) is highly controversial, we decided to do a retrospective analysis of patients treated in our office who had sustained whiplash injuries and were treated for cervical and temporomandibular disorders. The records of 300 patients with TMD preceded by a motor vehicle accident were examined retrospectively. The most common presenting symptoms, in order, were: jaw pain, neck pain, post-traumatic headache, jaw fatigue, and severe temporomandibular joint (TMJ) clicking. The most common TMD diagnoses were: masseter trigger points, closing jaw muscle hyperactivity, TMJ synovitis, opening jaw muscle hyperactivity, and advanced TMJ disk derangement. Based primarily on the physical examination, we concluded that the TMJ and surrounding musculature should be examined similarly to other joints, with no preconceived notion that TMD pathology after whiplash is unlikely.

A method for measuring interrater agreement on checklists.

A method for measuring interrater agreement on checklists is presented. This technique does not assign individual scores to raters, but computes a single agreement score from the concordance of their check mark configurations. An overall coefficient of agreement, called phi, is derived. The agreement coefficient that is expected by chance and the statistical significance of phi are determined by statistical simulation. Despite the dichotomous nature of the checklist agreement (raters either agree or disagree on items), we show that the binomial distribution does not provide a means for testing the statistical significance of phi. A medical education study is used to illustrate the phi methodology.

Effect of alterations in femoral artery flow on abdominal vessel hemodynamics in swine.

In support of an in vivo investigation in swine of the influence of changes in fluid dynamic wall shear on arterial macromolecular permeability, a procedure has been developed to alter the flows in the porcine posterior arterial vasculature by opening and closing a reversible arteriovenous shunt placed on one of the femoral arteries. Laparoscopic techniques were used to place appropriately modified Transonic Systems ultrasonic flow probes on both external and circumflex iliac arteries, and on the terminal aorta. Flow measurements were made prior to shunt placement, and with the shunt open and closed, to measure the influence of altered external iliac artery flow on the distribution to the infrarenal abdominal vessels. Similar experiments were carried out to relate the flow rates in the external iliac arteries to those in the femoral arteries, which are more accessible. Based on the relationships among the measured flow rates, rules have been developed to estimate the major infrarenal flows in the pig, at baseline and with the shunt opened and closed, from only the flow rates measured at the two femoral arteries.

Variability of the planarity of the human aortic bifurcation.

The susceptibility of vascular branches to atherosclerosis is believed to be due in part to the unusual fluid dynamic environments that the vessel wall experiences in these regions. As vascular geometry is a primary determinant of the local haemodynamic environment, it is of interest to quantitate the geometric features of vascular branches and their variability. The present research focusses on branch planarity, using axial magnetic resonance images of the aortic bifurcations of 20 healthy subjects. The in vivo images were processed to obtain vector representations of the vessel axes at the bifurcation, from which the planarity of the bifurcation was derived using a novel robust definition. Three-dimensional reconstructions of the bifurcations were rendered using computer graphics techniques to demonstrate the variability of the planarity of this region of the vasculature; this variability might be related to variable predispositions to atherosclerosis at the aortic bifurcation.

Dynamics of coronary artery curvature obtained from biplane cineangiograms.

A system was developed to track the centerlines (axes) of human coronary arteries during the cardiac cycle from biplane cineangiograms. The system employs a time interpolation technique on one image plane and a smoothing technique on the other to create simultaneous image pairs. The image pairs are then used to reconstruct the three dimensional axes of the vessels during the cardiac cycle. Once the vessel axes are reconstructed, acceleration, velocity and geometric parameters such as curvature can be obtained. In the present work, a sequence of human angiograms is used to obtain the axial and temporal variation of the curvature of a portion of the left anterior descending coronary artery distal to the third diagonal branch during two cardiac cycles. For the case studied, the change in curvature during the cycle ranged from 0.25 to 1.8 cm(-1), depending upon the position of the site.

Validated computation of physiologic flow in a realistic coronary artery branch.

The pulsatile flow field in an anatomically realistic model of the bifurcation of the left anterior descending coronary artery (LAD) and its first diagonal branch (D1) was simulated numerically and measured by laser Doppler anemometry. The inlet velocity profiles used in the computer simulation and in the physical experiments were physiologically realistic. The computational geometric model was developed on the basis of a digitized arterial cast. The curvature of the LAD over the cardiac surface leads to axial velocity profiles which are slightly skewed towards the epicardial wall. Downstream of the bifurcation, a strong skewing occurs towards the flow divider walls as a result of branching. Locally, the wall shear stress component caused by the complex secondary velocity can be as high as the axial component. The wall shear stress representation from a cell-based perspective exhibits low shear stress and large deviation from the time-averaged shear stress direction during systole. In diastole, the instantaneous wall shear stress direction nearly corresponds to the mean direction. The comparison of computed and measured axial velocity results shows generally good agreement. In contrast to computed flow patterns in simpler geometries constructed from cylindrical tubes, the flow field is found to be smoother, presumably reflecting the adaptation of the vascular contour to the contained flow.

Relation between the structural asymmetry of coronary branch vessels and the angle at their origin.

The relationship between the geometry of branch points on the left anterior descending coronary artery, and the morphometry of the proximal portions of the daughter vessels, was examined. The geometry at 23 branch points on 15 human hearts was derived from multiplane contrast angiograms, and the morphometry at 29 sites along the daughter vessels was obtained from transverse sections using computerized techniques. The angle of the branch at which the daughter originated was positively correlated with the maximum thicknesses of the intima and media, and with their circumferential asymmetry. The results suggest that large branch angles may favor eccentric intimal thickening, a phenomenon which may predispose to lipid accumulation and atherosclerosis.