Wael Shaalan

Transitional Flow at the Venous Anastomosis of an Arteriovenous Graft: Potential Activation of the ERK1/2 Mechanotransduction Pathway

We present experimental and computational results that describe the level, distribution, and importance of velocity fluctuations within the venous anastomosis of an arteriovenous graft. The motivation of this work is to understand better the importance of biomechanical forces in the development of intimal hyperplasia within these grafts. Steady-flow in vitro studies (Re = 1060 and 1820) were conducted within a graft model that represents the venous anastomosis to measure velocity by means of laser Doppler anemometry. Numerical simulations with the same geometry and flow conditions were conducted by employing the spectral element technique. As flow enters the vein from the graft, the velocity field exhibits flow separation and coherent structures (weak turbulence) that originate from the separation shear layer. We also report results of a porcine animal study in which the distribution and magnitude of vein-wall vibration on the venous anastomosis were measured at the time of graft construction. Preliminary molecular biology studies indicate elevated activity levels of the extracellular regulatory kinase ERK1/2, a mitogen-activated protein kinase involved in mechanotransduction, at regions of increased vein-wall vibration. These findings suggest a potential relationship between the associated turbulence-induced vein-wall vibration and the development of intimal hyperplasia in arteriovenous grafts. Further research is necessary, however, in order to determine if a correlation exists and to differentiate the vibration effect from that of flow related effects.

Human Carotid Plaque Calcification and Vulnerability

Background: Inflammation is a key mechanism in human atherosclerotic plaque vulnerability and disruption. The objective was to determine the differential gene expression of pro- and anti-inflammatory factors in the fibrous cap and shoulder region of noncalcified and calcified carotid endarterectomy plaques. Methods: Thirty carotid endarterectomy plaques were classified as type Va (noncalcified, n = 15) and type Vb (calcified, n = 15) in accordance with the American Heart Association consensus. Using laser capture microdissection, fibrous cap and shoulder regions were excisedfrom frozen sections. Gene expression of pro- [interleukin 1 (IL-1), IL-8 and monocyte chemoattractant protein 1 (MCP-1)] and anti-inflammatory (IL-10) factors, and bone formation (bone morphogenetic protein 6 and osteocalcin) mediators were quantitated by real-time PCR. Protein levels were determined using Western blotting. Results: Mean percent carotid stenosis and calcification area were 79 and 5% in Va-plaques (40% symptomatic) and 77 and 42% in Vb-plaques (20% symptomatic). Macrophages infiltrating the region of the fibrous cap and the shoulder were more numerous in non-calcified plaques compared with calcified plaques (p < 0.01]. mRNA expression of MCP-1 and IL-8, and protein levels of IL-8 were also greater in Va plaques compared to Vb plaques (p < 0.05). Protein levels and mRNA expression of osteocalcin were greater in Vb compared to Va plaques (p < 0.05). Conclusions: Fibrous cap inflammation is more likely to occur in noncalcified than in calcified plaques. These findings suggest that carotid atherosclerotic plaque calcification is a structural marker of plaque stability.

Reappraisal of velocity criteria for carotid bulb/internal carotid artery stenosis utilizing high-resolution B-mode ultrasound validated with computed tomography angiography

OBJECTIVE Reliability of the most commonly used duplex ultrasound (DUS) velocity thresholds for internal carotid artery (ICA) stenosis has been questioned since these thresholds were developed using less precise methods to grade stenosis severity based on angiography. In this study, maximum percent diameter carotid bulb ICA stenosis (European Carotid Surgery Trial [ECST] method) was objectively measured using high resolution B-mode DUS validated with computed tomography angiography (CTA) and used to determine optimum velocity thresholds for > or =50% and > or =80% bulb internal carotid artery stenosis (ICA). METHODS B-mode DUS and CTA images of 74 bulb ICA stenoses were compared to validate accuracy of the DUS measurements. In 337 mild, moderate, and severe bulb ICA stenoses (n = 232 patients), the minimal residual lumen and the maximum outer bulb/proximal ICA diameter were determined on longitudinal and transverse images. This in contrast to the North American Symptomatic Carotid Endarterectomy Trial (NASCET) method using normal distal ICA lumen diameter as the denominator. Severe calcified carotid segments and patients with contralateral occlusion were excluded. In each study, the highest peak systolic (PSV) and end-diastolic (EDV) velocities as well as ICA/common carotid artery (CCA) ratio were recorded. Using receiver operating characteristic (ROC) analysis, the optimum threshold for each hemodynamic parameter was determined to predict > or =50% (n = 281) and > or =80% (n = 62) bulb ICA stenosis. RESULTS Patients mean age was 74 +/- 8 years; 49% females. Clinical risk factors for atherosclerosis included coronary artery disease (40%), diabetes mellitus (32%), hypertension (70%), smoking (34%), and hypercholesterolemia (49%). Thirty-three percent of carotid lesions (n = 110) presented with ischemic cerebrovascular symptoms and 67% (n = 227) were asymptomatic. There was an excellent agreement between B-mode DUS and CTA (r = 0.9, P = .002). The inter/intraobserver agreement (kappa) for B-mode imaging measurements were 0.8 and 0.9, respectively, and for CTA measurements 0.8 and 0.9, respectively. When both PSV of > or =155 cm/s and ICA/CCA ratio of > or =2 were combined for the detection of > or =50% bulb ICA stenosis, a positive predictive value (PPV) of 97% and an accuracy of 82% were obtained. For a > or =80% bulb ICA stenosis, an EDV of > or =140 cm/s, a PSV of > or =370 cm/s and an ICA/CCA ratio of > or =6 had acceptable probability values. CONCLUSION Compared with established velocity thresholds commonly applied in practice, a substantially higher PSV (155 vs 125 cm/s) was more accurate for detecting > or =50% bulb/ICA stenosis. In combination, a PSV of > or =155 cm/s and an ICA/CCA ratio of > or =2 have excellent predictive value for this stenosis category. For > or =80% bulb ICA stenosis (NASCET 60% stenosis), an EDV of 140 cm/s, a PSV of > or =370 cm/s, and an ICA/CCA ratio of > or =6 are equally reliable and do not indicate any major change from the established criteria. Current DUS > or =50% bulb ICA stenosis criteria appear to overestimate carotid bifurcation disease and may predispose patients with asymptomatic carotid disease to untoward costly diagnostic imaging and intervention.

Is Atherectomy the Best First-Line Therapy for Limb Salvage in Patients With Critical Limb Ischemia?:

Objective: To determine the efficacy of atherectomy for limb salvage compared with open bypass in patients with critical limb ischemia. Methods: Ninety-nine consecutive bypass and atherectomy procedures performed for critical limb ischemia between January 2003 and October 2006 were reviewed. Results: A total of 99 cases involving TASC C (n = 43, 44%) and D (n = 56, 56%) lesions were treated with surgical bypass in 59 patients and atherectomy in 33 patients. Bypass and atherectomy achieved similar 1-year primary patency (64% vs 63%; P = .2). However, the 1-year limb salvage rate was greater in the bypass group (87% vs 69%; P = .004). In the tissue loss subgroup, there was a greater limb salvage rate for bypass patients versus atherectomy (79% vs 60%; P = .04). Conclusions: Patients with critical limb ischemia may do better with open bypass compared with atherectomy as first-line therapy for limb salvage.