C. G. Caro

Non-planar curvature and branching of arteries and non-planar-type flow

In this study, magnetic resonance imaging techniques have been used to examine the geometry of arterial curvature and branching in casts and in vivo, and to measure the distribution of axial velocity in the associated flow. It is found, contrary to a widely held view, that the geometry is commonly non-planar. Moreover, relatively small values of the parameters which render the geometry non-planar appear significantly to affect the velocity distribution. The findings suggest that non-planarity is an important factor influencing arterial flows, including wall shear. The implications are not restricted to vascular biology, pathology and surgery, but may extend to the design of general piping systems.

Discovery of the Role of Wall Shear in Atherosclerosis

The suggestion was made in the 1870s that mechanical irritation of the arterial wall is a cause of atherosclerosis, because the changes were chiefly found at points “exposed to the full stress and impact of the blood.” The mechanical damage theory persisted until well into the 20th century when, with interest increasing in multidisciplinary research, two fluid mechanical proposals were advanced for the patchy distribution of the lesions. One advocated high- and the other low-wall shear. Arterial wall shear stress levels appeared, however, insufficiently high to damage the endothelium. In contrast, examination of cadaver human arteries, combined with flow studies in models and casts of arteries, implied that the lesions occurred preferentially in regions expected to experience low-wall shear; a mechanism, involving arterial wall lipid metabolism and shear-dependent blood-wall mass transport, was suggested to account for that distribution. These proposals helped stimulate extensive investigation of arterial fluid mechanics/mass transport and vascular biology/pathology, revealing mechanisms that may explain the now widely confirmed preferred occurrence of atherosclerosis in low wall shear regions in adult human beings.

The Influence of Out-of-Plane Geometry on the Flow Within a Distal End-to-Side Anastomosis

This paper describes a computational and experimental investigation of flow in a proto-type model geometry of a fully occluded 45 deg distal end-to-side anastomosis. Previous investigations have considered a similar configuration where the centerlines of the bypass and host vessels lie within a plane, thereby producing a plane of symmetry within the flow. We have extended these investigations by deforming the bypass vessel out of the plane of symmetry, thereby breaking the symmetry of the flow and producing a nonplanar geometry. Experimental data were obtained using magnetic resonance imaging of flow within perspex models and computational data were obtained from simulations using a high-order spectral/hp element method. We found that the nonplanar three-dimensional flow notably alters the distribution of wall shear stress at the bed of the anastomosis, reducing the peak wall shear stress peak by approximately 10 percent when compared with the planar model. Furthermore, an increase in the absolute flux of velocity into the occluded region, proximal to the anastomosis, of 80 percent was observed in the nonplanar geometry when compared with the planar geometry.

Transport of 14C-4-Cholesterol between Serum and Wall in the Perfused Dog Common Carotid Artery

The transport of certain materials between the blood and the wall in arteries appears to be dependent on wall shear rate with shear rate–enhancing flux; however, the mechanism is unclear. If the transport is diffusional, it must involve three steps: diffusion across a boundary layer, uptake at the blood-wall interface, and transport within the wall. If the first step is rate controlling, if wall shear rate is spatially uniform, and if a diffusion boundary layer commences upstream at the junction between the vessel and an impermeable tube, then flux will be proportional to the cube root of wall shear rate divided by distance and will depend on the species diffusion coefficient. A dogs common carotid artery was perfused with serum containing 14C-4-cholesterol linked with lipoprotein; the fluid mechanics resembled those described above. In 20 experiments, there was no spatial dependence of uptake of the label, flux was lower by a factor of about a hundred than that predicted, and there was a suggestion (statistically nonsignificant) of shear dependence. The first two findings are inconsistent with transport controlled by the diffusion boundary layer. An uptake-controlled transport could be shear dependent.

Preliminary comparative study of small amplitude helical and conventional ePTFE arteriovenous shunts in pigs

Intimal hyperplasia (IH), which causes occlusion of arterial bypass grafts and arteriovenous (A-V) shunts, develops preferentially in low wall shear, or stagnation, regions. Arterial geometry is commonly three-dimensional, generating swirling flows, the characteristics of which include in-plane mixing and inhibition of stagnation. Clinical arterial bypass grafts are commonly two-dimensional, favouring extremes of wall shear. We have developed small amplitude helical technology (SwirlGraft) devices and shown them to generate physiological-type swirling flows. Expanded polytetrafluorethylene (ePTFE) grafts, although widely used as A-V shunts for renal dialysis access, are prone to thrombosis and IH. In a small preliminary study in pigs, we have implanted SwirlGraft ePTFE carotid artery-to-jugular vein shunts on one side and conventional ePTFE carotid artery-to-jugular vein shunts contralaterally. There was consistently less thrombosis and IH in the SwirlGraft than conventional shunts. At eight weeks (two animals), the differences were marked, with virtually no disease in the SwirlGraft devices and occlusion of the conventional grafts by thrombosis and IH. The study had limitations, but the lesser pathology in the SwirlGraft devices is likely to have resulted from their geometry and the associated swirling flow. The results could have implications for vascular biology and prolongation of the patency of arterial bypass grafts and A-V shunts.

Net albumin transport across the wall of the rabbit common carotid artery perfused in situ

We have studied the transport of radioactively labelled albumin in the rabbit common carotid artery perfused in situ at 100 cm H2O luminal pressure in the anaesthetized living animal, assessing the distribution of concentration across the wall by means of sequential frozen sectioning. We have compared the findings with those of experiments in which we have attempted to saturate the wall with label. Our findings support the belief that there is a net transport of macromolecules across the arterial wall. They show in addition that the wall is inhomogeneous. The distribution volume for label is greater in the adventitia than the media, which appears to offer a larger resistance. The transport process is seemingly dominantly diffusional.

The effect of varying albumin concentration of the hydraulic conductivity of the rabbit common carotid artery

Rabbit common carotid arteries were cannulated in situ, after ligation of their branches, and transferred to a perfusion apparatus in such a way that they were maintained at their physiological dimensions and the endothelium remained intact. The vessels were pressurized to 150 cm H2O with Krebs solution and the wall smooth muscle was relaxed with 10(-4) M NaNO2. The rate of inflow of perfusate into the vessels was measured by following the movement of a bubble in a calibrated capillary which, when steady, was taken to indicate the transmural filtration rate. The filtration rate was 1.48 +/- 0.26 X 10(-6) cm sec-1 (11) (mean, SD, n) with 1 g/dl bovine serum albumin in Krebs solution. The values with 0, 4, 7, and 10 g/dl, normalized by the 1 g/dl value were 1.38 +/- 0.16 (7), 0.80 +/- 0.05 (9), 0.65 +/- 0.03 (8), and 0.47 +/- 0.06 (9), respectively. The hydraulic conductivity of the wall was also found to depend on perfusate albumin concentration. The 1 g/dl value was 0.92 +/- 0.17 X 10(-8) cm sec-1 (cm H2O)-1 (11) and the values with 0, 4, 7 and 10 g/dl normalized by the 1 g/dl value were 1.35 +/- 0.16 (7), 0.87 +/- 0.06 (9), 0.81 +/- 0.03 (8), and 0.72 +/- 0.06 (9), respectively. The findings were analyzed in relation to models involving interaction of albumin with the endothelial glycocalyx, concentration polarization at the blood/wall interface, dependence of flux on solvent viscosity and dependence of the porosity of the wall interstitium on solvent flux. Both concentration polarization and variation of the porosity of the wall interstitium provide reasonable quantitative explanations for the findings.

Arterial geometry, flow pattern, wall shear and mass transport: potential physiological significance.

We have studied numerically steady and unsteady flow in a straight and a helically stented common carotid artery, in order to model porcine experimental results that show reduced intimal hyperplasia (IH) in the helical case. The combination of flow pulsatility and three-dimensionality generates a sweeping motion of the Dean vortices, which overall reduced extremes of both oxygen flux to the vessel wall and wall shear stress (WSS). Since IH and atherosclerosis affect preferentially low WSS regions, these findings imply that vessel three-dimensionality and flow pulsatility can play important protective roles in respect of these diseases. The amplitude and frequency of the velocity waveform are important parameters of the system. Increase in amplitude increases WSS and oxygen flux to the vessel wall. Increase in frequency has a small effect; it increases WSS but has no effect on the oxygen flux to the vessel wall.

Local and Global Geometric Influence on Steady Flow in Distal Anastomoses of Peripheral Bypass Grafts

We consider the effect of geometrical configuration on the steady flow field of representative geometries from an in vivo anatomical data set of end-to-side distal anastomoses constructed as part of a peripheral bypass graft. Using a geometrical classification technique, we select the anastomoses of three representative patients according to the angle between the graft and proximal host vessels (GPA) and the planarity of the anastomotic configuration. The geometries considered include two surgically tunneled grafts with shallow GPAs which are relatively planar but have different lumen characteristics, one case exhibiting a local restriction at the perianastomotic graft and proximal host whilst the other case has a relatively uniform cross section. The third case is nonplanar and characterized by a wide GPA resulting from the graft being constructed superficially from an in situ vein. In all three models the same peripheral resistance was imposed at the computational outflows of the distal and proximal host vessels and this condition, combined with the effect of the anastomotic geometry, has been observed to reasonably reproduce the in vivo flow split. By analyzing the flow fields we demonstrate how the local and global geometric characteristics influences the distribution of wall shear stress and the steady transport of fluid particles. Specifically, in vessels that have a global geometric characteristic we observe that the wall shear stress depends on large scale geometrical factors, e.g., the curvature and planarity of blood vessels. In contrast, the wall shear stress distribution and local mixing is significantly influenced by morphology and location of restrictions, particular when there is a shallow GPA. A combination of local and global effects are also possible as demonstrated in our third study of an anastomosis with a larger GPA. These relatively simple observations highlight the need to distinguish between local and global geometric influences for a given reconstruction. We further present the geometrical evolution of the anastomoses over a series of follow-up studies and observe how the lumen progresses towards the faster bulk flow of the velocity in the original geometry. This mechanism is consistent with the luminal changes in recirculation regions that experience low wall shear stress. In the shallow GPA anastomoses the proximal part of the native host vessel occludes or stenoses earlier than in the case with wide GPA. A potential contribution to this behavior is suggested by the stronger mixing that characterizes anastomoses with large GPA.

EFFECT OF CIGARETTE SMOKING ON THE PATTERN OF ARTERIAL BLOOD FLOW: POSSIBLE INSIGHT INTO MECHANISMS UNDERLYING THE DEVELOPMENT OF ARTERIOSCLEROSIS

By means of non-invasive multichannel doppler ultrasound measurements, cigarette smoking in healthy subjects was shown to increase arterial wall stiffness and to alter the pattern of arterial blood flow, decreasing the pulsatility index. The pattern of blood flow seems to be a contributory factor in the development of arteriosclerosis, and these findings may provide insight into the underlying mechanisms.