ABSTRACT
BACKGROUND: Constrictive vascular remodeling (VR) is the most significant component of restenosis after balloon angioplasty (PTA). Whereas in physiological conditions VR is associated with normalization of shear stress (SS) and wall stress (WS), after PTA the role of SS and WS in VR is unknown. Furthermore, whereas matrix metalloproteinase inhibition (MMPI) has been shown to modulate VR after PTA, its effect on the SS and WS control mechanisms after PTA is unknown. METHODS AND RESULTS: PTA was performed in external iliac arteries of 12 atherosclerotic Yucatan pigs, of which 6 pigs (7 vessels) received the MMPI batimastat and 6 pigs (10 vessels) served as controls. Before and after the intervention and at 6-week follow-up, intravascular ultrasound pullback was performed, allowing 3D reconstruction of the treated segment and computational fluid dynamics to calculate the media-bounded area and SS. WS was derived from the Laplace formula. Immediately after PTA, media-bounded area, WS, and SS changed by 20%, 16%, and -49%, respectively, in both groups. VR was predicted by SS and WS. In the control group, SS and WS had been normalized at follow-up with respect to the reference segment. In contrast, for the batimastat group, the SS had been normalized, but not the WS. The latter is attributed to an increase in wall area at follow-up. CONCLUSIONS: Vascular remodeling after PTA is controlled by both SS and WS. MMPI inhibited the WS control system.
Subject(s)
Angioplasty, Balloon , Arteriosclerosis/physiopathology , Matrix Metalloproteinase Inhibitors , Phenylalanine/analogs & derivatives , Phenylalanine/pharmacology , Thiophenes/pharmacology , Tunica Intima/drug effects , Animals , Arteriosclerosis/pathology , Arteriosclerosis/therapy , Feedback , Hemorheology , Iliac Artery/diagnostic imaging , Iliac Artery/drug effects , Iliac Artery/surgery , Matrix Metalloproteinases/metabolism , Models, Cardiovascular , Protease Inhibitors/pharmacology , Regression Analysis , Stress, Mechanical , Swine, Miniature , Tunica Intima/pathology , Ultrasonography , Vascular Patency/drug effectsABSTRACT
Mechanisms of in-stent restenosis are not fully understood. Shear stress is known to play a role in plaque and thrombus formation and is sensitive to changes in regional vessel geometry. Hence, we evaluated the regional changes in 3-D geometry and shear stress induced by stent placement in coronary arteries of pigs.Methods. 3-D reconstruction was performed, applying a combined angiographic and IVUS technique (ANGUS), from seven Wallstents (diameter 3.5 (n=3) and 5mm (n=4)), which were implanted in seven coronary arteries of five pigs. This 3-D geometry was used to calculate locally the curvature, while the shear stress distribution was obtained by computational fluid dynamics. Local changes in shear stress were obtained at the entrance and exit of the stent for baseline (0. 65+/-0.22 ml/s) and hyperemic flow (2.60+/-0.86 ml/s) conditions. Results. After stent implantation, the curvature increased by 121% at the entrance and by 100% at the exit of the stent, resulting in local changes in shear stress. In general, at the entrance of the stent local maxima in shear stress were generated, while at the exit both local maxima and minima in shear stress were observed (p<0.05). Additionally, the shear stress at the entrance and exit of the stent were correlated with the local curvature (r: 0.30-0.84).Conclusion. Stent implantation changes 3-D vessel geometry in such a way that regions with decreased and increased shear stress occur close to the stent edges. These changes might be related to the asymmetric patterns of in-stent restenosis.
Subject(s)
Coronary Vessels/physiopathology , Models, Cardiovascular , Stents , Animals , Hemodynamics , Stress, Mechanical , SwineABSTRACT
Shear stress plays a role in lipid accumulation in primary atherosclerosis and vascular remodelling. We will present applications of a new technique, which enables to quantify shear stress in 3D vessel reconstructions. The method is based on 3D IVUS reconstructions of blood vessels either obtained by IVUS pull back (external iliac artery) or by a combination of angiography and IVUS (curved coronary artery). Distribution of wall thickness of a curved human right coronary artery was such that low wall thickness occurred where shear stress was high, and wall thickness was high where shear stress was low. Consequently, an inverse relationship between shear stress and wall thickness was detected. Although vascular remodelling after PTA in external iliac arteries of atherosclerotic Yucatan pigs was predicted both by acute gain and decrements in shear stress, the decrement in shear stress appeared a better predictor. In conclusion, shear stress appears to play a role in primary atherosclerosis and vascular remodelling after PTA.
