Proceedings of The Physiological Society

University of Oxford (2011) Proc Physiol Soc 23, C79

Oral Communications

Arterial stent intimal hyperplasia: role of hypoxia and blood-wall oxygen transport

C. Caro1, A. Seneviratne2, C. Monaco2, D. Hou3, J. Singh3, M. Burke4, K. Heraty4, R. Krams1, G. Coppola1

1. Bioengineering, Imperial College London, London, United Kingdom. 2. Kennedy Institute of Rheumatology, Imperial College London, London, United Kingdom. 3. Saint Joseph's Translational Research Institute, Atlanta, Georgia, United States. 4. Veryan Medical Limited, Horsham, United Kingdom.

Intimal hyperplasia (IH) causes failure of interventions, but its causation is unclear. Low wall shear is implicated at bypass grafts and wall damage at stents. In addition, stenting deforms arteries, inducing wall hypoxia 1, 2 but that occurrence has attracted limited attention. Our interest in stent-associated IH arose because: oxygen transport between luminal blood and arterial wall is fluid-phase controlled; arterial sites which experience low wall shear may be hypoxic; and arterial curvature and branching are commonly non-planar, generating swirling and cross-mixing which can increase wall shear and blood-wall mass transport, including of oxygen 3 . In previously published work we developed a stent with a helical centreline, implanting it (US Laboratory Animal Welfare Act) in one common carotid artery (CCA) of 10 healthy pigs, and a conventional (straight) stent contralaterally. The former stent deformed vessels helically, causing swirling and cross-mixing of flow. At sacrifice, one month after implantation, transverse sections showed significantly less intimal thickening in helically-stented than straight-stented vessels 4. To increase understanding, we measured in the same sections intimal thickness and medial area, and calculated average intima-media ratio (IMR) and total adventitial area. We also counted adventitial vessels (circular or quasi-circular contours) under low power magnification - average number per section: helical 130; straight 220. Vessel number was not correlated with section thickness, consistent with the measurement procedure. The results are therefore presented as vessel density per unit adventitial area. IMR was significantly lower in helically-stented than straight-stented arteries (0.75±0.66 vs 1.20±0.35, p<0.01) as was adventitial vessel density (40.1±;16.8 vs 61.0±26.6, p<0.01). Less intimal thickening in helically-stented than straight-stented CCAs is not readily explained by wall damage. Inspection of arterial sections suggested helical stents caused wall thinning at convex helical bends and wall thickening at concave helical bends. Helical stenting can generate several fluid mechanical changes, including luminal cross-mixing, which can increase wall shear stress and convective blood-wall mass transport, including of oxygen. These effects are not readily distinguished. However, if adventitial vessel density can be considered surrogate for wall hypoxia, it is implied that wall hypoxia was less in helically-stented than straight-stented CCAs, consistent with the importance of conduit geometry and intraluminal mixing, and with wall hypoxia being a significant causative factor for IH. Supportive of that view, supplementary oxygen reduced the severity of IH after arterial stenting in animals 5.

Where applicable, experiments conform with Society ethical requirements