Localizing role of hemodynamics in atherosclerosis in several human vertebrobasilar junction geometries.

Atherosclerosis is a common finding in the vertebrobasilar junction and in the basilar artery. Several theories try to link the process of atherogenesis with the forces exerted by the flowing blood. An attractive relation has been found between the locations in vessels at which atherosclerotic plaques are often present and the locations in models where complicated flow patterns exist. Most of the studies provided data on bifurcations. Finding a similar relation in an arterial confluence would certainly add to the credibility of the (causal) relationship between hemodynamics and atherosclerosis. Further support can be provided if variations of the geometry result in changes of the location of the atherosclerotic lesions, corresponding to the changes of the flow force distribution. In our previous numerical and experimental work, the influence of geometric and hemodynamic parameters, such as asymmetrical inflow, confluence angle, and blunting of the apex, on the flow in vertebrobasilar junction models has been investigated in detail. Recirculation areas and distribution of the wall shear stress have been computed. In this anatomic study, the effect of modulation of these geometric and hemodynamic parameters on the flow pattern is compared with the size and location of plaques in human vertebrobasilar junctions and basilar arteries. In addition, a comparison is made between the preferential areas of atherosclerotic plaques in junctions and bifurcations to demonstrate the localizing role of hemodynamics in atherogenesis. The apex of the vertebrobasilar junction and the lateral walls of the basilar artery appeared to be prone to atherosclerosis. In 43 of 85 vertebrobasilar junctions, a plaque was found at the apex. Furthermore, the summed plaque thickness at both lateral walls differs significantly (paired t test, P=.03) from that at the walls facing the pons and the skull base. In contrast, several authors found that the lateral walls of the mother vessel and the apex in bifurcations are often spared. Modulation of the various parameters in the models changed the size of the regions with low wall shear stress and/or recirculation areas dramatically. A comparable effect was found in the occurrence of plaques in the human vertebrobasilar junction; eg, for an atherosclerotic plaque at the apex, a predicted probability larger than 0.5 was computed for blunted apexes and for sharp-edged apexes with a confluence angle exceeding 90 degrees. Apparently, two geometric risk factors for an atherosclerotic plaque at the apex can be distinguished: a blunted apex and a large confluence angle.

The influence of the blunting of the apex on the flow in a vertebro-basilar junction model.

The apex of human vertebro-basilar junctions can be sharp-edged or blunted. In the present study, the effect of blunted apex on the flow in vertebro-basilar junction models is investigated. We compared the flow phenomena in a series of junction models with blunted apices and confluence angles 45, 85, and 125 deg with the flow phenomena in a series of junction models with sharp-edged apices and the same range of confluence angles, studied in a previous paper (Ravensbergen et al., 1996b). The blunting of the apex appears to have an effect on the size of the local recirculation area near the apex and the prevailing low velocities. Large recirculation areas are found in the models with blunted apices, especially in those with small confluence angles. In addition, the blunting of the apex has no influence on the flow further downstream, nor on the structure and strength of the secondary flow field. Furthermore, a blunted apex appears to be a geometric risk factor for atherosclerosis. This supports the hypotheses that recirculation areas and low wall shear stress influence the development of atherosclerotic plaques.

The influence of the angle of confluence on the flow in a vertebro-basilar junction model.

In earlier work, it was demonstrated that the flow in models of the vertebro-basilar junction is highly three-dimensional and the geometry exerts a strong influence on the hemodynamics. The morphology of the vertebro-basilar junction is very variable amongst individuals. In a study of 85 human vertebro-basilar junctions, the angle between the vertebral arteries varied between 10 and 160 degrees. To determine how the flow is influenced by this geometrical parameter, the flow is studied both experimentally, with laser Doppler velocimetry, and numerically, with a finite element package. A series of junction models is used with a range of confluence angles (45, 85 and 125 degrees). It appears that the angle of confluence has a strong influence on the structure and strength of the secondary flow field. The secondary velocities persist far downstream. Furthermore, near the apex, a region with low velocities is present. The larger the confluence angle is, the larger this region is, and even backflow may occur. In addition, the occurrence of atherosclerotic plaques in 85 human vertebro-basilar junctions is studied. Only one preferential location was found: the apex, the other plaques seem to be randomly distributed. The magnitude of the confluence angle of junctions with sharp-edged apices has a significant influence (p = 0.006) on the occurrence of a plaque at the apex. Apparently, a large confluence angle is a geometrical risk factor for atherosclerosis.

New ways of performing in vivo flow velocity measurements in the basilar artery.

The basilar artery is the only large artery in which two flows merge, and this is reflected in the flow downstream. We report quantitative flow-velocity measurements with a phase-based MR technique, i.e. the Fourier velocity encoding method, in the basilar artery of a volunteer. To our knowledge, this has not previously been performed successfully. A comparison is made with the results of flow velocity measurements in the basilar artery with transcranial Doppler ultrasonography; the techniques agreed very well. Although Doppler ultrasonography is still most widely used, no information on the flow rate and the flow velocity distribution in the basilar artery can be provided. MR flow measurement techniques appear promising when detailed information on the flow velocity distribution and flow rate is needed.

Porphyrins and metalloporphyrins: potential hypoxic agents.

Synthetic water-soluble porphyrins and their metalloporphyrin derivatives with Co(III), Cu(II), Ru(II) and Pt(II), containing various functional groups within the meso-positions of the porphyrin, were synthesised and evaluated as hypoxic agents, especially as cytotoxins and radiosensitisers. Cobalt complexes of the porphyrins containing positively charged methylpyridinium groups showed selective toxicity toward hypoxic Chinese Hamster Ovary (CHO) cells. The Co(III) complexes of the cationic and the anionic porphyrins are all weak radiosensitisers toward hypoxic cells, the highest sensitisation enhancement ratio (SER = 1.22, at 50 muM) being with a porphyrin complex containing a cis-arrangement of two nitro and two methylpyridinium meso-substituents. A copper complex of a tetracationic porphyrin showed slight radiosensitisation activity with an SER value of about 1.1. The other metalloporphyrins showed no hypoxic selectivity or radiosensitisation activity. In total, over 50 porphyrin free bases have been synthesised, of which half are water-soluble and have been metallated; thus, the chemistry is now in place for further development of water-soluble hypoxic agents.

Computation of steady three-dimensional flow in a model of the basilar artery.

The flow in the basilar artery arises from the merging of the flows from the two vertebral arteries. To study the flow phenomena in the basilar artery, computations have been performed using a finite element (FE) method. We consider steady flow in a geometrically symmetric confluence. For simplicity, channels with a rectangular cross-section have been used. Both symmetric and asymmetric flow cases have been considered. The results show that for the Reynolds number of interest the flow downstream of the junction is highly three-dimensional, and that the flow at the end of the basilar artery, where it splits again, will not be fully developed. The computed phenomena have been confirmed by laser Doppler velocity measurements.

Renal dysfunction after angiography; a risk factor analysis in patients with peripheral vascular disease.

Angiography is required for a detailed anatomical investigation before reconstructive surgery or percutaneous transluminal angioplasty can be performed. Although angiography is a safe procedure, it is associated with renal dysfunction, usually transient, in about 10% of the cases. This study concentrates on the evaluation of renal dysfunction induced by "conventional" (i.e. film-screen) Seldinger angiography and a consecutive series of 396 angiographic procedures have been evaluated. Induced Renal Dysfunction was defined as an increase of more than 10% in the serum creatinine after angiography. To identify "risk factors" for Induced Renal Dysfunction we have studied whether clinical and angiographical variables were associated with the occurrence of Induced Renal Dysfunction. These variables included: age, hypertension, the use of antihypertensive drugs, diabetes mellitus, technique of angiography, site of contrast injection and type and quantity of contrast medium. Induced Renal Dysfunction was found in 21 cases (5.7%) and appeared to be associated with age above 70, hypertension, administration of more than 150 ml contrast medium and the presence of renal disease prior to angiography. More than 95% of the 21 patients with dysfunction had two or more of these "risk factors". The presence of diabetes was not clearly associated with Induced Renal Dysfunction and haemodialyses was not required in any of the patients. The incidence of Induced Renal Dysfunction after angiography was 5.7% which is low but not negligible. However, renal dysfunction was always transient and never severe. Furthermore, the identification of "risk factors" allows the prompt identification of patients at risk before angiography, which may help to reduce the incidence of Induced Renal Dysfunction.