Human carotid plaque calcification and vulnerability. Relationship between degree of plaque calcification, fibrous cap inflammatory gene expression and symptomatology.

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 excised from 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.

Total laparorobotic repair of abdominal aortic aneurysm with sac exclusion obliteration and aortobifemoral bypass.

A 65-year-old man with coronary artery disease, hypertension, and peripheral vascular disease was found to have an asymptomatic abdominal aortic aneurysm (AAA) of 5.5 cm on surveillance for his peripheral vascular disease. Cardiac stress testing demonstrated no evidence of myocardial ischemia, and he opted to undergo open repair of his aneurysm. Laparorobotic repair of the infrarenal AAA using the da Vinci robotic system was performed with an aortobifemoral bypass. We describe a novel technique for AAA exclusion using a cerclage method, which greatly facilitates repair of infrarenal AAAs using laparorobotic techniques. Laparorobotic repair of infrarenal AAA can be greatly facilitated by AAA sac exclusion and obliteration without the need to ligate all lumbar arteries or to open the aneurysm. This virtually avoids blood loss from the sac and minimizes the possibility for open conversion as a result of poor visualization. Minimally invasive aortic intervention for aneurysmal disease using laparascopic methods has been reported in the literature. Problems associated with this technique include a prolonged learning curve and difficulty completing intracorporeal anastomoses. Robotic surgery provides an advantage over laparoscopic surgery in its ability to provide greater degrees of freedom in a relatively small field of view along with superior high-definition, three-dimensional visualization. To date, there have been no known reports of using robotic surgery in the United States as a sole method for repair of AAA. We report our technique of combining robotic surgery with a novel procedure for sac exclusion and obliteration to successfully repair AAA without the need for opening the aneurysm sac and endoaneurysmorrhaphy.

WITHDRAWN: Reappraisal of internal carotid artery stenosis velocity thresholds utilizing high-resolution B-mode ultrasound validated with computed tomography angiography (CTA).

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Direct numerical simulation of transitional flow in a stenosed carotid bifurcation.

The blood flow dynamics of a stenosed, subject-specific, carotid bifurcation were numerically simulated using the spectral element method. Pulsatile inlet conditions were based on in vivo color Doppler ultrasound measurements of blood velocity. The results demonstrated the transitional or weakly turbulent state of the blood flow, which featured rapid velocity and pressure fluctuations in the post-stenotic region of the internal carotid artery (ICA) during systole and laminar flow during diastole. High-frequency vortex shedding was greatest downstream of the stenosis during the deceleration phase of systole. Velocity fluctuations had a frequency within the audible range of 100-300Hz. Instantaneous wall shear stress (WSS) within the stenosis was relatively high during systole ( approximately 25-45Pa) compared to that in a healthy carotid. In addition, high spatial gradients of WSS were present due to flow separation on the inner wall. Oscillatory flow reversal and low pressure were observed distal to the stenosis in the ICA. This study predicts the complex flow field, the turbulence levels and the distribution of the biomechanical stresses present in vivo within a stenosed carotid artery.

Importance of flow division on transition to turbulence within an arteriovenous graft.

Transitional blood flow in an arteriovenous graft under various conditions of flow division was examined through direct numerical simulation. This junction consists of an inlet vessel (prosthetic graft) connected to a host vessel (vein) at an acute angle (21.6 degrees ). Inlet Reynolds numbers, based on mean velocity and graft inlet diameter, ranged from 800 to 1400. Various flow divisions between the two ends of the host vessel (i.e., the proximal venous segment, PVS, and distal venous segment, DVS) were considered (PVS:DVS ratios of 100:0, 85:15, 70:30 and 115:(15)). The numerical technique employed the spectral element method which is a high-order discretization ideally suited to the simulation of transitional flows in complex domains. High velocity and pressure fluctuations were observed for the PVS:DVS=70:30 and 85:15 cases and absent from the 100:0 and 115:(15) cases; the results indicate the importance of flow division on the development of turbulence in this junction. Transition to turbulence was observed at Reynolds numbers as low as 1000 and 800 under flow divisions of 85:15 and 70:30, respectively, significantly lower than the critical value of 2100. The frequency spectra of velocity fluctuations indicated a significant intensity within the frequency range of approximately 300Hz downstream of the junction. An adverse pressure gradient developed in the PVS when graft inflow divided into opposite directions in the junction. This pressure gradient had a destabilizing effect on the flow and enhanced transition to turbulence in the PVS. These findings suggest that measurements of in vivo flow rates at the inlet and outlets are critical for the accurate prediction of arteriovenous hemodynamics. A potential clinical application of these results might be to close off the DVS during graft construction to ensure a 100:0 flow division.

B-mode ultrasound measurement of carotid bifurcation stenoses: is it reliable?

In the majority of cases, duplex ultrasonography (DU) is the sole imaging study necessary before carotid interventions. Duplex-derived internal carotid artery (ICA) peak systolic velocity (PSV), ICA end-diastolic velocity (EDV) and ICA/common carotid artery (CCA) PSV ratio are the most commonly utilized parameters for predicting critical carotid stenoses. However, the role of direct B-mode image measurement of maximal ICA narrowing is ill defined. The images and records of 192 patients who underwent both arteriography and duplex ultrasonography (DU) of 375 carotid arteries from January 1995 to November 2000 were reviewed. All DUs were performed by registered vascular technologists (n=6). Maximum arteriographic stenosis was determined according to the NASCET study design. With arteriography as the "gold standard," B-mode image (BMI) measurement of the maximal ICA luminal narrowing relative to the carotid bulb (n=162)as well as the peak systolic velocity in the internal carotid artery (PSVICA) (n=330), end-diastolic velocity in the internal carotid artery (EDV(ICA)) (n=198), and the ratio of the PSVs in both the ICA and the CCA (PSVICA/CCA) ratio (n=319) were subjected to receiver operator characteristics (ROC) curves for 3 clinically relevant stenoses thresholds: 50-99%, 60-99%, and 70-99%. A strong correlation was found between B-mode image (BMI)and the NASCET arteriographic measures of carotid stenosis (r =0.80;p<0.001) and was similar among the 6 technologists (r =0.74-0.89;p>0.2). The overall accuracy of BMI measurement to diagnose 50%, 60%,and 70% arteriographic carotid stenosis was 85.3%, 82.2%, and 87%, respectively. BMI measurement was similar to the most accurate PSV(ICA), EDV(ICA), and PSV(ICA/CCA) ratio at all 3 threshold stenoses levels (p>0.3). When combined with the velocity criteria, BMI measurement improved the positive predictive value (PPV) for all arteriographic stenoses thresholds by an average of 12.6% for PSV(ICA), 21.2% for EDV(ICA), and 14.2% for PSV(ICA/CCA) ratio. BMI measurement of carotid bifurcation narrowing is as reliable as duplex-derived velocity criteria in evaluating clinically relevant threshold ICA stenoses. The routine use of B-mode ultrasound in conjunction with the velocity parameters enhances the PPV of carotid DU. Our experience suggests that with current refinements in B-mode resolution, BMI stenosis measurements are accurate among experienced technologists and are a useful adjunct to duplex-derived velocity parameters.

Routine early postoperative duplex scanning is unnecessary following uncomplicated carotid endarterectomy.

Although early postoperative duplex scanning has become routine after carotid endarterectomy (CEA), it is unclear whether the results of these scans alter clinical management. The purpose of this study was to critically examine the usefulness of early postoperative duplex scans in evaluating the ipsilateral carotid artery (for technical perfection) as well as the contralateral carotid artery (for potential velocity changes after improvements in ipsilateral flow). Consecutive patients undergoing CEA between January 1995 and June 1999 in a tertiary hospital setting were studied. Patients underwent early postoperative duplex scanning according to the discretion of the operating surgeon and the availability of the patient. In 212 patients 236 CEAs were performed with selective use of patch closure (49%), intraluminal shunting (19%), and intraoperative completion imaging studies (14%). Neurologic complications included 3 transient ischemic attacks (TIAs) (1.3%), 3 nondisabling strokes (1.3%), and 3 disabling strokes (1.3%). There was 1 30-day death from myocardial infarction. Patients were followed up for a median of 18 months (range 0-72 months). Sixty-five percent of patients undergoing uncomplicated CEA (147/227) underwent early duplex surveillance within 6 months of operation. Unsuspected sonographic abnormalities were discovered in 8 patients (5%), including 7 cases of mild internal carotid artery (ICA) stenosis (>50% by velocity criteria) and 1 case of common carotid artery (CCA) stenosis (intimal flap). None of the patients with ICA stenosis developed symptoms or required operation at any time. The CCA intimal flap was electively repaired without complication. Postoperative changes in velocity in the contralateral ICA were found in 8/48 (17%) cases. There were 3 cases of increased velocity, upgrading 1 from 0-49% to 50-79% stenosis and upgrading 2 from 50-79% to 80-99% stenosis. The latter patients both underwent uneventful contralateral CEA. There were 6 cases of decreased velocity, resulting in downgrading of stenoses from 50-79% to 0-49% (n=5) or from 80-99% to 50-79% (n=1). Only the latter patient underwent contralateral CEA; the remainder have been followed up without intervention. Early scanning appeared to offer no clinical benefit; survival and neurologic outcome were the same in the 135 patients scanned within the first 6 months as in the 68 patients whose first postoperative scan occurred later (4-year neurologic event rate 0% in both groups; patient survival with early duplex 98 +/- 1.5%, without early duplex 96 +/- 2.6%; = NS). Early ipsilateral duplex abnormalities following CEA are infrequent in asymptomatic patients and, even if found, rarely alter management. Patients with bilateral stenosis being considered for contralateral CEA should undergo repeat duplex scanning after the first operation, because of the significant rate (19%) of contralateral velocity changes induced by ipsilateral CEA.

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.

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.

Acoustic radiation from a fluid-filled, subsurface vascular tube with internal turbulent flow due to a constriction.

The vibration of a thin-walled cylindrical, compliant viscoelastic tube with internal turbulent flow due to an axisymmetric constriction is studied theoretically and experimentally. Vibration of the tube is considered with internal fluid coupling only, and with coupling to internal-flowing fluid and external stagnant fluid or external tissue-like viscoelastic material. The theoretical analysis includes the adaptation of a model for turbulence in the internal fluid and its vibratory excitation of and interaction with the tube wall and surrounding viscoelastic medium. Analytical predictions are compared with experimental measurements conducted on a flow model system using laser Doppler vibrometry to measure tube vibration and the vibration of the surrounding viscoelastic medium. Fluid pressure within the tube was measured with miniature hydrophones. Discrepancies between theory and experiment, as well as the coupled nature of the fluid-structure interaction, are described. This study is relevant to and may lead to further insight into the patency and mechanisms of vascular failure, as well as diagnostic techniques utilizing noninvasive acoustic measurements.

B-mode ultrasonographic characterization of carotid atherosclerotic plaques in symptomatic and asymptomatic patients.

OBJECTIVE: To identify features on B-mode ultrasonography (US) prevalent in symptomatic plaques and correlate these findings with histopathologic markers of plaque instability. METHODS: Carotid endarterectomy (CEA) plaques from symptomatic and asymptomatic patients with critical stenoses (>70%) were qualitatively assessed using preoperative B-mode US for echolucency and calcific acoustic shadowing. US echolucency was quantitated ex vivo using computerized techniques for gray-scale median (GSM) analysis. Histopathologic correlates for US plaque echolucency (percentage of necrotic core area) and acoustic shadowing (percentage of calcification area) were determined. RESULTS: Fifty CEA plaques were collected from 48 patients (46 unilateral and two bilateral); 26 of these plaques were from symptomatic patients. Age, degree of stenosis, and atherosclerotic risk factors were similar for the symptomatic and asymptomatic patients. Using preoperative B-mode US, 58%, 35%, and 7% of symptomatic plaques and 18%, 41%, and 41% of asymptomatic plaques were found to be echolucent, echogenic, and calcific, respectively (P < .05). Using ex-vivo B-mode US and GSM analysis, symptomatic plaques were more echolucent (41 +/- 19) than asymptomatic plaques (60 +/- 13), P < .03. A strong inverse correlation was found between the percent plaque necrotic area core and GSM (R = -0.9, P < .001). Percentage of calcification area in plaques with acoustic shadowing was 66% and only 27% in those without acoustic shadowing (P < .05). CONCLUSIONS: Using B-mode US, symptomatic plaques are more echolucent and less calcified than asymptomatic plaques and are associated with a greater degree of histopathologic plaque necrosis. Such features are indicative of plaque instability and should be considered in the decision-making algorithm when selecting patients with high-grade asymptomatic carotid stenosis for intervention.

Reliability of common femoral artery hemodynamics in assessing the severity of aortoiliac inflow disease.

OBJECTIVES: We investigated the utility of color duplex ultrasound (CDU)-derived common femoral artery (CFA) hemodynamics for detecting significant aortoiliac occlusive disease and predicting its severity. METHODS: From January 1997 to June 2001, 132 consecutive patients with lower extremity arterial insufficiency underwent both femoropopliteal CDU scanning and aortography with runoff studies. CDU-derived CFA waveform contour (monophasic, biphasic, or triphasic), peak systolic velocity (PSV), and acceleration time were recorded for each patient. Severity of aortoiliac occlusive disease was classified by arteriography into three distinct groups: normal or minimal disease (<50%, group 1), significant focal or diffuse stenoses (>/=50%, group 2), or total occlusion (group 3). Using probability and receiver operating characteristic curve analysis, waveform contour and PSV were compared alone and in combination with the arteriographic groups to identify waveform contours and threshold PSV, which may accurately differentiate the three categories of aortoiliac occlusive disease. RESULTS: Of 214 limbs available for study, 112 composed group 1, 70 composed group 2, and 32 composed group 3. Concomitant femoropopliteal disease was present in 47% of limbs in group 1, 53% of limbs in group 2, and 34% of limbs in group III. An abnormal CFA waveform contour (monophasic or biphasic) differentiated group 1 from groups 2 and 3, with 95% sensitivity, 89% specificity, 89% positive predictive value (PPV), 95% negative predictive value (NPV), and 92% accuracy. Mean PSV and acceleration time for monophasic and biphasic waveforms were 39 cm/sec +/- 19, 178 msec +/- 36 vs 95 cm/sec +/- 67, 97 msec +/- 31 respectively (P <.05). In differentiating between groups 2 and 3, the specificity, PPV, and accuracy for CFA PSV of

Diurnal heart rate reactivity: a predictor of severity of experimental coronary and carotid atherosclerosis.

BACKGROUND: Elevated awake resting heart rate (HR) has been shown to be a major risk factor for cardiovascular disease. Since coronary ischaemic events appear to peak during transition from sleep to awake HR, we sought to determine whether the degree of diurnal HR fluctuation (dHRV) is an independent predictor of coronary and peripheral atherogenesis. In this study, we varied both baseline HR and dHRV using sino-atrial node ablation (SNA) in a primate model of diet-induced atherogenesis and determined the degree of plaque formation relative to both HR parameters. METHODS: HR was recorded continuously for 6 months by an implantable intraaortic sensor/transmitter in 17 active unrestricted male cynomolgus monkeys. In nine monkeys, SNA was employed to create a wide spectrum of dHRV, and the power amplitude of dHRV was determined for the daily HRV cycle with power spectral analysis. After a 6-month diet induction period, percent coronary and carotid stenosis, intimal thickness and area were quantitated in each animal. RESULTS: Total serum cholesterol and mean HR were no different between high ( n= 10) and low ( n= 7) dHRV groups (866 mg% vs. 740 mg%, P> 0.2 and 130 +/- 22 and 115 +/- 13, P> 0.1, respectively). Percent carotid stenosis was markedly greater in both high HR and dHRV animals ([HR], 54 +/- 19 vs. 35 +/- 10, P< 0.04) and ([dHRV], 54 +/- 17 vs. 32 +/- 10, P< 0.01). Significant increases in all measures of coronary atherogenesis were found in high dHRV animals when compared with those with low dHRV (percent stenosis: 48% +/- 22 vs. 23% +/- 16, P< 0.02), (lesion area: 1.2 +/- 0.8 vs. 0.3 +/- 0.3, P< 0.02), and (intimal thickness: 0.3 +/- 0.1 vs. 0.1 +/- 0.1, P< 0.01), respectively. While there was a trend towards greater coronary atherogenesis in animals with high HR, this did not reach statistical significance. CONCLUSION: Elevated HR and dHRV are both associated with enhanced experimental atherosclerotic plaque formation. However, a greater degree of carotid and coronary atherogenesis is observed in animals with high dHRV. These findings suggest that elevated dHRV is a stronger predictor for susceptibility to atherogenesis than elevated HR alone. Such a relationship may be attributed to the potential role of dHRV in modulating the frequency of adverse near wall haemodynamic forces, which have been shown to induce atherosclerotic plaques. Lowering of dHRV in humans by exercise or pharmacological agents may have a beneficial role in retarding atherosclerotic plaque induction, progression and complication.

Differential mechanical activation of mitogen-activated protein kinases in intact human blood vessels.

BACKGROUND: Vascular tissue remodels in response to a variety of hemodynamic factors, often transduced through activation of mitogen-activated protein kinases such as extracellular signal-related kinase (ERK1/2) and c-jun N-terminal kinase (JNK). This study tests the hypothesis that these kinases are involved in mechanical signal transduction in intact human arteries and veins. METHODS: Unused portions of human saphenous vein and radial artery were obtained fresh at the time of peripheral or coronary bypass. A sample of the vessel was immediately snap frozen (control(0)) and the remainder separated into three segments. One segment was placed in sterile medium and left undisturbed for 2 h (control(2)), one was perfused with sterile medium for 2 h at a steady rate of 150 ml/min, yielding shear stress values of 8-20 dyne/cm(2) (flow), and one was statically pressurized without flow at 110 mm Hg for 2 h (pressure). After treatment, samples were tested for phosphorylated ERK1/2 and JNK using Western blot. RESULTS: Two hours of culture produced mild increases in ERK1/2 activity in both vessel types. Stimulation with continuous rapid flow produced significantly increased ERK1 activity and a nearly 100% increase in ERK2 in veins. Static pressurization also stimulated ERK1/2, although slightly less than continuous flow. ERK1/2 phosphorylation was only mildly increased in flow-stimulated radial arteries, and exposure to normal systemic pressure showed no appreciable effect. Significant phosphorylation of JNK was not observed in either vessel. CONCLUSION: ERK1/2 phosphorylation is increased in human saphenous veins and radial arteries exposed to the hemodynamic conditions of arterial grafting. This pathway may be involved in the transduction of external stimuli leading to remodeling.

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.

Relative contribution of wall shear stress and injury in experimental intimal thickening at PTFE end-to-side arterial anastomoses.

BACKGROUND: Intimal hyperplastic thickening (IHT) is a frequent cause of prosthetic bypass graft failure. Induction and progression of IHT is thought to involve a number of mechanisms related to variation in the flow field, injury and the prosthetic nature of the conduit. This study was designed to examine the relative contribution of wall shear stress and injury to the induction of IHT at defined regions of experimental end-to-side prosthetic anastomoses. METHODS AND RESULTS: The distribution of IHT was determined at the distal end-to-side anastomosis of seven canine Iliofemoral PTFE grafts after 12 weeks of implantation. An upscaled transparent model was constructed using the in vivo anastomotic geometry, and wall shear stress was determined at 24 axial locations from laser Doppler anemometry measurements of the near wall velocity under conditions of pulsatile flow similar to that present in vivo. The distribution of IHT at the end-to-side PTFE graft was determined using computer assisted morphometry. IHT involving the native artery ranged from 0.0+/-0.1 mm to 0.05+/-0.03 mm. A greater amount of IHT was found on the graft hood (PTFE) and ranged from 0.09+/-0.06 to 0.24+/-0.06 mm. Nonlinear multivariable logistic analysis was used to model IHT as a function of the reciprocal of wall shear stress, distance from the suture line, and vascular conduit type (i.e. PTFE versus host artery). Vascular conduit type and distance from the suture line independently contributed to IHT. An inverse correlation between wall shear stress and IHT was found only for those regions located on the juxta-anastomotic PTFE graft. CONCLUSIONS: The data are consistent with a model of intimal thickening in which the intimal hyperplastic pannus migrating from the suture line was enhanced by reduced levels of wall shear stress at the PTFE graft/host artery interface. Such hemodynamic modulation of injury induced IHT was absent at the neighboring artery wall.

Degree of carotid plaque calcification in relation to symptomatic outcome and plaque inflammation.

OBJECTIVE: We undertook this study to quantitate differences in the degree of calcification between symptomatic and asymptomatic plaques removed at carotid endarterectomy (CEA) and to determine associated extent of plaque macrophage infiltration, a histopathologic feature of plaque instability. METHODS: CEA plaques (n = 48) were imaged at 1.25-mm intervals with spiral computed tomography (CT; 10-15 images per plaque). Indications for CEA were transient ischemic attack (n = 16), stroke (n = 5), amaurosis (n = 4), and critical asymptomatic stenosis (n = 23). The percent area calcification for each plaque was determined in spiral CT serial sections and averaged for each plaque. In 31 of 48 plaques macrophage infiltration was quantitated in corresponding histologic sections with immunohistochemical techniques. RESULTS: The mean (+/- SD) age of patients with symptomatic and asymptomatic plaques was 66 +/- 7 years vs 71 +/- 7 years, respectively, and degree of stenosis was 76% versus 82%, respectively (P =.05). Atherosclerosis risk factors were similar between groups. Percent plaque area calcification was twofold greater in asymptomatic versus symptomatic plaques (48% +/- 19% vs 24% +/- 20%, respectively; P <.05). At receiver operating characteristic curve analysis, 80% of symptomatic plaques were below and 87% of asymptomatic plaques were above a cutoff point of 30% plaque area calcification. Macrophage burden was greater in the symptomatic plaques than in the asymptomatic plaques (52% vs 23%; P <.03). A strong inverse relationship between the degree of plaque calcification and macrophage infiltration was found in critical carotid stenoses (r = -0.87; P <.001). CONCLUSIONS: Symptomatic plaques are less calcified and more inflamed than asymptomatic plaques. Regardless of clinical outcome, a strong inverse correlation was found between the extent of carotid plaque calcification and the intensity of plaque fibrous cap inflammation as determined by the degree of macrophage infiltration. Carotid plaque calcification is associated with plaque stability, and is a potential spiral CT in vivo quantitative marker for cerebrovascular ischemic event risk.

Long-term outcome of infrainguinal bypass grafting in patients with serologically proven hypercoagulability.

OBJECTIVE: The purpose of this study was to test the hypothesis that the long-term outcome of infrainguinal bypass grafting in patients with congenital or acquired hypercoagulability is inferior to the results in patients without documented clotting disorders. METHODS: The study was a retrospective analysis of consecutive patients from January 1994 to January 2001. RESULTS: Five hundred eighty-two infrainguinal bypass grafts were created in 456 patients. Indication for surgery was limb-threatening ischemia in 84%; prosthetic conduits were implanted in 38%. Seventy-four grafts were created in 57 patients with one or more serologically proven hypercoagulable states, including heparin-induced platelet aggregation (n = 37), anticardiolipin antibodies (n = 11), lupus anticoagulant (n = 8), protein C or S deficiency (n = 7), antithrombin III deficiency (n = 3), and factor V Leiden mutation (n = 1). Patients with hypercoagulability were younger (63 +/- 2 years versus 69 +/- 1 years; P =.007), more likely to have undergone prior revascularization attempts (38% versus 21%; P =.003), and more likely to have chronic anticoagulation therapy after surgery (46% versus 25%; P =.001). After 5 years (median follow-up, 19 months), patients with hypercoagulability had poorer primary patency (28% +/- 7% versus 35% +/- 5%; P =.004), primary assisted patency (37% +/- 7% versus 45% +/- 6%; P =.0001), secondary patency (41% +/- 7% versus 53% +/- 6%; P =.0001), limb salvage (55% +/- 8% versus 67% +/- 6%; P =.009), and survival (61% +/- 8% versus 74% +/- 4%; P =.02) rates. Multivariate analysis identified only prosthetic conduit choice (P =.0001), hypercoagulability (P =.0003), and limb salvage indication (P =.01) as independent predictors of graft failure. CONCLUSION: Patients with serologically proven hypercoagulability have inferior long-term patency, limb salvage, and survival rates after infrainguinal bypass. The high prevalence rate (13%) of diverse hypercoagulable states in this patient population supports serologic screening, especially in referral practices.

Limb salvage after infrainguinal bypass graft failure.

OBJECTIVE: The purpose of this study was to examine the outcome of patients in whom an infrainguinal bypass graft failed. METHODS: This was a retrospective analysis of consecutive patients undergoing infrainguinal bypass grafting in a single institution over 8 years. RESULTS: Six hundred thirty-one infrainguinal bypass grafts were placed in 578 limbs in 503 patients during the study period. The indication for surgery was limb-threatening ischemia in 533 patients (85%); nonautologous conduits were used in 259 patients (41%), and 144 (23%) were repeat operations. After a mean follow-up of 28 +/- 1 months (median, 23 months; range, 0-99 months), 167 grafts (26%) had failed secondarily. The rate of limb salvage in patients with graft failure was poor, only 50% +/- 5% at 2 years after failure. The 2-year limb salvage rate depended on the initial indication for bypass grafting: 100% in patients with claudication (n = 16), 55% +/- 8% in patients with rest pain (n = 49), and 34% +/- 6% in patients with tissue loss (n = 73; P <.001). The prospect for limb salvage also depended on the duration that the graft remained patent. Early graft failure (<30 days; n = 25) carried a poor prognosis, with 2-year limb salvage of only 25% +/- 10%; limb salvage was 53% +/- 5% after intermediate graft failure (<2 years, n = 110) and 79% +/- 10% after late failure (>2 years, n = 15; P =.04). Multivariate analysis revealed shorter patency interval before failure (P =.006), use of warfarin sodium (Coumadin) postoperatively (P =.006), and infrapopliteal distal anastomosis (P =.01) as significant predictors for ultimate limb loss. CONCLUSION: The overall prognosis for limb salvage in patients with failed infrainguinal bypass grafts is poor, particularly in patients with grafts placed because of tissue loss and those with early graft failure.

Conduit choice for above-knee femoropopliteal bypass grafting in patients with limb-threatening ischemia.

Many surgeons consider PTFE to be the conduit of choice for above-knee femoropopliteal bypass grafting, since PTFE is relatively easy to implant and spares autogenous saphenous vein (ASV) for subsequent peripheral or coronary artery bypass grafting (CABG). This practice has recently been challenged, as some studies have suggested that ASV may exhibit superior patency in certain patient subgroups. The purpose of this retrospective study was to examine the contemporary outcome of above-knee femoropopliteal bypass grafting in patients with limb-threatening ischemia. Between January 1995 and December 2000, 159 above-knee femoropopliteal bypass grafts were created for limb-threatening ischemia (rest pain or tissue loss). There was a high incidence of comorbid illness, including open foot wounds at the time of operation (62%), hypertension (58%), coronary artery disease (53%), diabetes mellitus (36%), cerebrovascular disease (23%), prior contralateral bypass or amputation (21%), disadvantaged or "blind" outflow (19%), prior ipsilateral bypass (14%), prior CABG (11%) end-stage renal failure (7%). The use of PTFE predominated (n = 11), with a minority of grafts comprising single-segment ipsilateral or contralateral ASV (n = 18). Although the small number of patients undergoing ASV grafting limited the statistical power of comparison, our results suggest that above-knee ASV performs better than PTFE in patients with limb-threatening ischemia.