Development Of Stenotic Lesions Research Articles

Treatment of an Unyielding Central Vein Stenosis using Valvuloplasty Balloon in a Young Female Presenting with Ineffective Hemodialysis

Abstract Percutaneous balloon venoplasty is widely employed for the management of central vein stenosis (CVS), a condition frequently encountered in patients on maintenance hemodialysis (MHD). The hypertrophied and fibrotic venous stenotic lesions often pose a challenge for interventionists, due to resistance to dilatation and high-elastic recoil. We report here successful utilization of mitral valvuloplasty balloon for percutaneous treatment of an unyielding brachiocephalic vein stenosis. Repeated failure of conventionally used peripheral balloon dilatation catheter prompted the use of a mitral valvuloplasty balloon that could exert higher radial pressure while preventing melon-seeding and hence successfully achieve stenosis dilatation. The mitral valvuloplasty balloon can be effectively and safely used for lesions resistant to repeated dilatations by conventional peripheral balloons. Rheological stress on central veins from ipsilateral arteriovenous fistula (AVF) may result in development of stenotic lesions, even in the absence of prior venous catheterization of the affected vein; therefore, in the presence of relevant symptoms, this diagnosis should not be excluded on the basis of absence of prior direct trauma at the stenosis site.

Computational haemodynamics analysis and comparison study of arterio-venous grafts

Haemodialysis arterio-venous graft failure is related to the development of stenotic lesions most commonly located near the venous anastomosis, especially in the toe region. 'Disturbed flow' interaction with the vessel wall surface, characterized by haemodynamic parameters based on the local wall shear stress or the radial pressure gradient, have been widely recognized as the trigger mechanism of a cascade of abnormal biological events leading to occlusive developments. Assuming incompressible laminar flow and rigid, in-plane vessel walls, validated haemodynamics are numerically simulated for a constant-diameter end-to-side base case, the VenafloTM graft, and an improved graft-end configuration. The geometric design of the new graft-end was based on the reduction of three time- and area-averaged haemodynamic parameters, i.e. the wall shear stress gradient, wall shear stress angle gradient, and radial pressuregradient. Considering the critical toeregion, the VenafloTM graft has demonstrated measurable improvements over the base case configuration in predictive computer simulations as well as in clinical trials. The performance improvement should be further enhanced with the modifications illustrated by the new design.

Regulation of smooth muscle cell migration and integrin expression by the Gax transcription factor.

Homeobox transcription factors specify body plan by regulating differentiation, proliferation, and migration at a cellular level. The homeobox transcription factor Gax is expressed in quiescent vascular smooth muscle cells (VSMCs), and its expression is downregulated by vascular injury or other conditions that lead to VSMC proliferation. Previous investigations demonstrate that Gax may regulate VSMC proliferation by upregulating the cyclin-dependent kinase (cdk) inhibitor p21. Here we examined whether Gax influences VSMC migration, a key feature in the development of stenotic lesions after balloon injury. Transduction of a Gax cDNA inhibited the migratory response of VSMCs toward PDGF-BB, basic fibroblast growth factor, or hepatocyte growth factor/scatter factor. Gax expression also inhibited migration of NIH.3T3 fibroblasts and embryonic fibroblasts lacking p53. Gax was unable to inhibit the migration of fibroblasts lacking p21, but this effect could be restored in these cells by providing exogenous p21 or by overexpressing another cdk inhibitor, p16. Flow cytometric analysis implicated a Gax-mediated downregulation of alpha(v)beta(3) and alpha(v)beta(5) integrin expression in VSMCs as a potential cause for reduced cell motility. Gax specifically downregulated beta(3) and beta(5) in VSMCs in culture and after acute vascular injury in vivo. Repression of integrin expression was also found in NIH 3T3 cells and p53 knockout fibroblasts, but not in p21-knockout fibroblasts, unless these cells express exogenous p21 or p16. These data suggest that cycle progression, integrin expression, and cell migration can be regulated in VSMCs by the homeobox gene product Gax.

Factors Influencing the Development of Vein-graft Stenosis and their Significance for Clinical Management

Objectivesto assess the influence of clinical and graft factors on the development of stenotic lesions. In addition the implications of any significant correlation for duplex surveillance schedules or surgical bypass techniques was examined.Patients and methodsin a prospective three centre study, preoperative and peroperative data on 300 infrainguinal autologous vein grafts was analysed. All grafts were monitored by a strict duplex surveillance program and all received an angiogram in the first postoperative year. A revision was only performed if there was evidence of a stenosis of 70% diameter reduction or greater on the angiogram.Resultsthe minimum graft diameter was the only factor correlated significantly with the development of asignificant graft stenosis(PSV-ratio ≥2.5) during follow-up (p=0.002). Factors that correlated with the development ofevent-causing graft stenosis, associated with revision or occlusion, were minimal graft diameter (p=0.001), the use of a venovenous anastomosis (p=0.005) and length of the graft (p=0.025). Multivariate regression analysis revealed that the minimal graft diameter was the only independent factor that significantly correlated with anevent-causing graft stenosis(p=0.009). The stenosis-free rates for grafts with a minimal diameter <3.5 mm, between 3.5–4.5 and ≥4.5 mm were 40%, 58% and 75%, respectively (p=<0.05). Composite vein and arm-vein grafts with minimal diameters ≥3.5 mm were compared with grafts which consisted of a single uninterrupted greater saphenous vein with a minimal diameter of <3.5 mm. One-year secondary patency rates in these categories were of 94% and 76%, respectively (p=0.03).Conclusionsa minimal graft diameter <3.5 mm was the only factor that significantly correlated with the development of a graft-stenosis. However, veins with larger diameters may still develop stenotic lesions. Composite vein and arm-vein grafts should be used rather than uninterrupted small caliber saphenous veins.

Carvedilol, a cardiovascular drug, prevents vascular smooth muscle cell proliferation, migration, and neointimal formation following vascular injury.

Carvedilol is a cardiovascular drug currently used for the treatment of hypertension. Clinical studies have recently demonstrated efficacy in angina and congestive heart failure. Recently, carvedilol has been shown to attenuate oxygen free radical-initiated lipid peroxidation and to inhibit vascular smooth muscle mitogenesis induced by a wide variety of growth factors. These findings are of interest since smooth muscle proliferation and abnormal lipid metabolism are proposed to play an important role in the pathogenesis of atherosclerotic plaque formation and in development of stenotic lesions following vascular injury by balloon angioplasty and coronary artery bypass grafting. On the basis of these observations, the antiproliferative actions of carvedilol have been explored in detail. In human cultured pulmonary artery vascular smooth muscle cells, carvedilol (0.1-10 microM) produced a concentration-dependent inhibition of the mitogenesis stimulated by platelet-derived growth factor, epidermal growth factor, thrombin, and serum, with IC50 values ranging from 0.3 to 2.0 microM. Carvedilol also produced a concentration-dependent inhibition of vascular smooth muscle cell migration induced by platelet-derived growth factor, with an IC50 value of 3 microM. The extensive neointimal formation that occurs following balloon angioplasty of rat carotid arteries was markedly attenuated by carvedilol (1 mg/kg, i.p.; twice daily starting 3 days before angioplasty and continuing until 14 days after angioplasty). Quantitative image analysis demonstrated that carvedilol reduced the neointimal growth following angioplasty by 84% without altering either medial or adventitial cross-sectional areas. These observations indicate that carvedilol may also be effective in the treatment of pathological disorders principally associated with abnormal vascular smooth muscle growth, such as atherosclerosis and acute vascular wall injury induced by angioplasty or coronary artery bypass grafting.

Endothelin-1 promotes neointima formation after balloon angioplasty in the rat.

The long-term efficacy of percutaneous transluminal coronary angioplasty (PTCA) is severely limited by the high incidence of vascular restenosis. Endothelin-1 (ET-1) has been implicated in the pathogenesis of this response, since circulating levels of this potent smooth-muscle mitogen are elevated after PTCA. Therefore, this study examined the effect of exogenous ET-1 administration on the development of stenotic lesions in the rat common carotid artery angioplasty model. Immediately after left common carotid artery balloon angioplasty, rats received a 30-min i.a. infusion of either saline vehicle (0.9% NaCl w/v) or ET-1 (17 pmol kg-1 min-1) via the left external carotid artery. Left and right common carotid arteries were removed 7 days later for quantitative image analysis. Balloon angioplasty caused significant neointima proliferation in left common carotid arteries, the extent of which was increased significantly by acute ET-1 treatment (approximately 65% greater neointima formation relative to saline-treated rats). ET-1 treatment had no effect on the geometry of contralateral right common carotid arteries. Therefore, these data support a role for ET-1 in the pathogenesis of vascular restenosis.

Secondary femoropopliteal reconstruction.

Retrospective analysis of the authors' experience with 109 primary femoropopliteal bypass vein grafts that failed allows description of three distinct modes of failure. Within 30 days of surgery, failure resulted primarily from technical or judgmental errors. The development of stenotic lesions within the vein graft caused a second group of failures during the first year after bypass. The third group most commonly failed due to progression of peripheral atherosclerosis a year or more following original bypass. No correlation was found, however, between the mode of failure and results of secondary femoropopliteal-tibial reconstruction, which yielded an overall 50% five-year cumulative limb salvage rate. The results indicate that this salvage rate can be anticipated regardless of the number of secondary operations required. The highest long-term patency rate was achieved when frequent postoperative follow-up examinations allowed recognition of graft failure prior to total occlusion. Under such circumstances a simple vein patch of stenotic lesions yielded an 85% five-year graft patency. Following actual thrombosis, however, the highest five-year patency rate was achieved when reconstruction was performed using a new vein graft; saphenous vein and arm vein were equally effective. When prosthetic material was used, no secondary graft remained patent beyond three years. Finally, when a proximal or distal portion of the original vein graft proved adequate in caliber following thrombectomy, it could be successfully incorporated in a secondary reconstruction with the expectation of a 50% five-year limb salvage rate. No statistically significant difference was found in salvage rates among each of the patient groups representing the three common modes of graft failure. This finding, coupled with an acceptable 2.5% operative mortality rate, provides justification for an aggressive approach toward secondary femoropopliteal reconstruction.