How secure is the anastomosis between the proximal and distal body components of a fenestrated stent-graft?

OBJECTIVES: To examine the longitudinal migratory force required to cause disconnection of the bifurcated distal body component from the tubular proximal body of a fenestrated stent-graft. METHODS: Using a previously reported mathematical model distal distraction forces were calculated prior to performing in vitro pullout testing. The top end of the proximal body and the iliac limbs of the distal body were attached to the grips of a tensile tester via plastic sealing plugs and pneumatic clamps. Channels within the plugs allowed pressurisation of the inside of the stent-graft. Pullout tests were conducted in the vertical plane. Force and displacement data were recorded and tests repeated 8 times at room temperature with the stent-grafts either dry or wet and unpressurized, at 100 mmHg or at 120 mmHg. RESULTS: The median maximum pullout force was 2.9 N (2.6-4.1) when dry, 3.9 N (3.5-5.4) when wet and unpressurized, 6.3 N (4.8-8.3) when wet and pressurized at 100 mmHg and 6.5 N (4.8-7.2) when wet and pressurized at 120 mmHg. There was a significant difference between pressurized and unpressurized conditions (P < 0.01). CONCLUSIONS: The force required to distract the distal bifurcated component of a fenestrated stent graft is much lower than the reported proximal fixation strength of both a standard and fenestrated Zenith stent graft. Although this helps protect the fenestrated proximal body from the effects of longitudinal migration forces in vivo the current strength of the body overlap zone may actually be unnecessarily weak and requires careful surveillance in follow up.

Anchoring barbs and balloon expandable stents: what is the risk of perforation and failed stent deployment?

PURPOSE: Balloon expandable stents may on occasion be deployed in close proximity to the anchoring barbs of endovascular grafts. The aim of this study was to determine the risk and effect of balloon perforation by anchoring barbs and to assess whether these risks are different if the balloon is protected by a covered stent mounted upon it. METHODS: A bench-top model was developed to mimic the penetration of anchoring barbs into the lumen of medium sized blood vessels. The model allowed variation of angle and depth of vessel penetration. Both bare balloons and those with covered stents mounted upon them were tested in the model to determine whether there was a risk of perforation and which factors increased or decreased this risk. RESULTS: All combinations of barb angle and depth caused balloon perforation but this was most marked when the barb was placed perpendicular to the long axis of the balloon. When the deployment of covered stents was attempted balloon perforation occurred in some cases but full stent deployment was achieved in all cases where the perforation was in the portion of the balloon covered by the stent. The only situation in which stent deployment failed was where the barb was intentionally placed in the uncovered portion of the balloon. This resulted in only partial deployment of the stent. CONCLUSIONS: Balloon rupture is a distinct possibility when deploying balloon-expandable stents in close proximity to anchoring barbs. Care should be taken in this circumstance to ensure that the barb is well away from the uncovered portion of the balloon.

Reprinted article "Factors associated with early failure of arteriovenous fistulae for haemodialysis access".

The radiocephalic arteriovenous fistula remains the method of choice for haemodialysis access. In order to assess their suitability for fistula formation, the radial arteries and cephalic veins were examined preoperatively by ultrasound colour flow scanner in conjunction with a pulse-generated run-off system. Intraoperative blood flow was measured after construction of the fistulae. Post-operative follow-up was performed at various intervals to monitor the development of the fistulae. Radial artery and cephalic vein diameter less than 1.6 mm was associated with early fistula failure. The intraoperative fistula blood flow did not correlate with the outcome of the operation probably due to vessel spasm from manipulation. However, blood flow velocities measured non-invasively 1 day after the operation were significantly lower in fistulae that failed early compared with those that were adequate for haemodialysis. Most of the increase in fistula diameter and blood flow occur within the first 2 weeks of surgery.

Measurement of pulsatile haemodynamic forces in a model of a bifurcated stent graft for abdominal aortic aneurysm repair.

The longitudinal haemodynamic force (LF) acting on a bifurcated stent graft for abdominal aortic aneurysm repair has been estimated previously using a simple one-dimensional analytical model based on the momentum equation which assumes steady flow of an inviscid fluid. Using an instrumented stent-graft model an experimental technique was developed to measure the LF under pulsatile flow conditions. The physical stent-graft model, with main trunk diameter of 30mm and limb diameters of 12 mm, was fabricated from aluminium. Strain gauges were bonded on to the main trunk to determine the longitudinal strain which is related to the LF. After calibration, the model was placed in a pulsatile flow system with 40 per cent aqueous glycerol solution as the circulating fluid. The LF was determined using a Wheatstone bridge signal-conditioning circuit. The signals were averaged over 590 cardiac cycles and saved to a personal computer for subsequent processing. The LF was strongly dependent on the pressure but less so on the flowrate. The measured forces were higher than those predicted by the simplified mathematical model by about 6-18 per cent during the cardiac cycle. The excess measured forces are due to the viscous drag and the effect of pulsatile flow. The peak measured LF in this model of 30 mm diameter may exceed the fixation force of some current clinical endovascular stent grafts.

Physics-based virtual environment for training core skills in vascular interventional radiological procedures.

Recent years have seen a significant increase in the use of Interventional Radiology (IR) as an alternative to open surgery. A large number of IR procedures commences with needle puncture of a vessel to insert guidewires and catheters: these clinical skills are acquired by all radiologists during training on patients, associated with some discomfort and occasionally, complications. While some visual skills can be acquired using models such as the ones used in surgery, these have limitations for IR which relies heavily on a sense of touch. Both patients and trainees would benefit from a virtual environment (VE) conveying touch sensation to realistically mimic procedures. The authors are developing a high fidelity VE providing a validated alternative to the traditional apprenticeship model used for teaching the core skills. The current version of the CRaIVE simulator combines home made software, haptic devices and commercial equipments.

A new device for in vitro evaluation of thrombogenicity.

A device to measure the time of coagulation of whole blood has been designed in order to facilitate testing of thrombogenicity of biomaterials. The principle of operation of the apparatus is to record the time taken for a sphere to fall through a sample of blood. The coagulation time is defined here as the time from collection of the blood sample to coagulation, coagulation having deemed to have occurred when the sphere is prevented from falling by the presence of the fibrin-cell network. The device was tested with homogeneous fluids of different viscosity, milk containing different amounts of rennin and calcium chloride and non anti-coagulated whole blood obtained from five volunteers. Repeat measurements made with each homogeneous fluid show that the variance in the transit time of the sphere is small and consistent with small dispersion. In contrast, the onset of coagulation in milk and blood samples was readily detected. The clotting of milk was highly dependant on the concentration of rennin and calcium chloride. The coagulation time of blood samples from five individuals ranged from 23 to 33 min but simultaneous measurements of samples from the same individual in two identical devices agreed to within +/-1 min in all cases. This device may be easily adapted for use in studies to determine the thromboresistance of biomaterials where the onset of coagulation of whole blood in contact with different materials may be readily compared.

Swirling flow pattern in a non-planar model of an interposition vein cuff anastomosis.

One of the main causes of long-term failure of ePTFE grafts is the development of anastomotic intimal hyperplasia which leads to graft thrombosis. Experimental studies with bypass grafts have shown an inverse relationship between mean wall shear stress and intimal hyperplasia. The geometry of the anastomosis has a strong influence on the flow pattern and wall shear stress distribution. The aim of this in vitro study was to investigate the influence of non-planarity in a model of a distal anastomosis with interposition vein cuff, an anastomosis configuration that is increasingly being used because of improved clinical results. Laser Doppler anemometer measurements were carried out in silicone rubber models of interposition vein cuff anastomoses with planar and non-planar inflow. The pulsatile flow waveforms were typical of those found in femoro-infrapopliteal bypass. Axial and radial velocities were measured in the proximal and distal outflow segments. As expected a symmetrical helical flow pattern (Dean flow) was evident in the planar model. The model with non-planar inflow, however, gave rise to swirling flow in both the distal and proximal artery outflow segments for during the systolic phase. In patients, the anastomosis is usually non-planar. Since the configuration depends in part upon the tunnelling of the graft, this may be altered to some extent. Non-planar anastomotic configurations induce a swirling flow pattern, which may normalise wall shear stress, thereby potentially reducing intimal hyperplasia.

Exaggerated sensitivity to NE-induced vasoconstriction in IDDM patients with microalbuminuria. Possible etiology and diagnostic implications.

Increased urinary albumin excretion rate (AER) in the microalbuminuric phase of diabetic nephropathy has been attributed to intraglomerular hypertension. This could be caused by constriction of efferent glomerular arterioles, which carry alpha-adrenoceptors. We tested the hypothesis that insulin-dependent diabetes mellitus (IDDM) patients with microalbuminuria are hypersensitive to vasoconstriction induced by norepinephrine (NE). We studied 15 IDDM patients with microalbuminuria (AER 32-295 mg/24 h), 13 IDDM patients with normal AER (5-24 mg/24 h), and 9 nondiabetic subjects (AER 8-22 mg/24 h). All were normotensive. NE-induced vasoconstriction was measured in dorsal hand veins, which carry alpha-receptors similar to those of glomerular efferent arterioles. Vein diameter was measured with a linear displacement probe during a stepped NE infusion (1-32 ng/min) into the vein, and venoconstriction was expressed as a percentage of the maximum passively distended venous diameter. Microalbuminuric IDDM patients exhibited significantly greater vasoconstriction (P less than 0.005) at all NE infusion rates than both other groups. The NE infusion rate producing 50% of maximal venoconstriction (ED50) in the microalbuminuric IDDM group (median 1.1 ng/min, range 0.2-25.2 ng/min) was significantly less than in both the normoalbuminuric IDDM group (median 12.5 ng/min, range 4.9-40.5 ng/min, P = 0.00007) and the nondiabetic group (median 17.7 ng/min, range 5.9-42.2 ng/min, P = 0.0003). Dose-response curves and ED50 did not differ significantly between normalbuminuric IDDM and nondiabetic groups. IDDM patients with microalbuminuria are hypersensitive to NE-induced vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)

Attachment, morphology and adherence of human endothelial cells to vascular prosthesis materials under the action of shear stress.

In an effort to improve the long-term patency of vascular prostheses several groups now advocate seeding autologous endothelial cells (ECs) onto the lumen of the vessel prior to implantation, a procedure that involves pre-treating the prosthesis material with fibrin, collagen and/or other matrix molecules to promote cell attachment and retention. In this study, we examined the degree to which human umbilical venous endothelial cells (HUVECs) adhered to three materials commonly used polymeric vascular prosthesis that had been coated with the same commercial extra cellular matrix proteins, and after exposure to fluid shear stresses representative of femoro-distal bypass in a cone-and-plate shearing device. We quantified cell number, area of coverage and degree of cell spreading using image analysis techniques. The response of cells that adhered to the surface of each material, and following exposure to fluid shear stress, depended on surface treatment, topology and cell type. Whereas collagen coating improved primary cellular adhesion and coverage significantly, the degree of spreading depended on the underlying surface structure and on the application of the shear stress. In some cases, fewer than 30% of cells remained on the surface after only 1-h exposure to physiological levels of shear stress. The proportion of the surface that was covered by cells also decreased, despite an increase in the degree to which individual cells spread on exposure to shear stress. Moreover, the behaviour of HUVECs was distinct from that of fibroblasts, in that the human ECs were able to adapt to their environment by spreading to a much greater extent in response to shear. The quality of HUVEC attachment, as measured by extent of cell coverage and resistance to fluid shear stress, was greatest on expanded polytetrafluoroethylene samples that had been impregnated with Type I/III collagen.

Removing fresh tissue from explanted polyurethane prostheses: which approach facilitates physico-chemical analysis?

Chemical, physical and structural analyses of polymers from explanted vascular prostheses are frequently jeopardized because of incomplete removal of the encroaching host tissue. In this study, microporous polyurethane arterial prostheses implanted as a canine thoraco-abdominal bypass were explanted after 1 and 12 months and were cleaned without fixation using four different digesting enzyme treatments, including collagenase, pancreatin and trypsin alone and collagenase and pancreatin in series, followed by washing in a solution of Triton X-100 detergent. By following this approach all the fresh tissue attached to the external and internal walls of the prostheses was removed with minimal damage to the underlying synthetic polymer. The morphology of the explanted and cleaned polyurethane prostheses could be obtained readily by light and scanning electron microscopy. Surface microporous features and the presence of polyurethane microfibres that had experienced in vivo biodegradation could therefore be identified easily. The surface and bulk physico-chemical properties of the polyurethane polymer were determined by electron spectroscopy for chemical analysis, attenuated total reflectance-Fourier transform infrared spectroscopy and differential scanning calorimetry. It was found that the most successful approach for removing fresh tissue and exposing a clean and uncontaminated polyurethane surface was to incubate the explanted samples first in collagenase followed by digestion in pancreatin. This particular cleaning technique has proved valuable in enabling us to monitor small in vivo changes in the surface chemistry and in the bulk microphase segmented structure of polyurethane biomaterials.

Chemical and morphological analysis of explanted polyurethane vascular prostheses: the challenge of removing fixed adhering tissue.

During in vivo experiments to evaluate the biocompatibility and biostability of alternative biomaterials, the ideal protocol for the handling and preservation of the explanted material is often compromised in order to meet the needs of both the pathologist and the materials scientist. Explants surrounded by tissue are often fixed in formalin or glutaraldehyde to facilitate later pathological and histological analysis, but the subsequent removal of such fixed tissue from thermally sensitive and less chemically stable polymers, such as polyurethanes, poses major problems for the materials scientist, who does not wish to modify the chemical, physical or morphological characteristics of the underlying biomaterial. The present study has attempted to find a solution to this problem by exposing virgin specimens of the microporous polyurethane Vascugraft vascular prosthesis to six different cleaning conditions, all known to be effective in removing fixed tissue. These conditions included the use of 20% aqueous potassium hydroxide solution for 48 h at room temperature, 5% sodium bicarbonate solution for 5 min at the boil, and 9, 10, 11 and 12N hydrochloric acid for 48 h at room temperature. The appearance and chemical properties of the virgin and treated specimens were compared using electron spectroscopy for chemical analysis, Fourier transform infrared spectroscopy, gel permeation chromatography for molecular weight and differential scanning calorimetry techniques. The use of temperatures close to the boil resulted in the formation of a translucent, rubbery material with gross changes in the microporous and microfibrous structure. The strongly acidic and alkaline conditions caused a loss in the surface carbonate group content. In addition, 12N hydrochloric acid reduced the molecular weight and urethane content. Consequently, 9N hydrochloric acid is recommended as the cleaning agent of choice for removing fixed tissue from this type of microporous polyurethane. Control experiments on virgin material should also be included in any cleaning protocol.

Pulsatile velocity distribution and wall shear rate measurement using pulsed Doppler ultrasound.

Instantaneous pulsatile velocity profiles were measured in a cylindrical tube using a 20 MHz pulsed Doppler ultrasound system. The spatial resolution of the device was improved with deconvolution using a procedure which employed frequency-domain windowing to suppress high-frequency noise. After deconvolution both the instantaneous velocity profiles and flow waveforms were compared with established theoretical predictions and good agreement was obtained. The average error in a velocity measurement was 7.9 +/- 0.9%, and the average error in the flow rate was 4.7 +/- 1.7%. The wall shear rate was determined from the gradient of the velocity profile both before and after deconvolution. The results were compared to the theoretical value of wall shear rate to quantify the accuracy of the technique under pulsatile flow conditions. Although the velocity profiles agreed well with theory, the wall shear rate was obtained less accurately. The average error in the mean wall shear rate and peak-to-peak wall shear rate was 28 +/- 7% and 11 +/- 3%, respectively. However, some of this discrepancy, was attributed to the method of evaluation. In all cases deconvolution significantly improved the accuracy of the wall shear rate determination.

Flow patterns in an endovascular stent-graft for abdominal aortic aneurysm repair.

Endovascular exclusion of the abdominal aortic aneurysm (AAA) has been carried out in selected patients during the past decade. The deployment of a complex multicomponent endovascular device in an aneurysmal aorta may alter the local haemodynamics and lead to thrombosis and intimal hyperplasia development. The aim of this in vitro study was to investigate the flow patterns using flow visualisation and laser Doppler anemometry in a commercial bifurcated stent-graft. Two configurations of the stent-graft, endo-stent and exo-stent, were investigated in an idealised planar AAA model. The flow structures in the main trunk in both configurations of the stent-graft are three-dimensional with complex secondary structures. However, these flow structures were not entirely caused by the stent-graft. The stent struts in the endo-stent configuration cause localised alteration in the flow pattern but the overall flow structures were not significantly affected. Low velocity regions in the main trunk and flow separation in the stump region and the curved segment of the iliac limbs were observed. These areas are associated with thrombosis in the clinical situation. Improvements in the design of endovascular devices may remove these areas of unfavourable flow patterns and lead to better clinical performance.

Effects of geometry and flow division on flow structures in models of the distal end-to-side anastomosis.

Flow structures in models of the distal end-to-side anastomosis were visualised under steady and pulsatile flow conditions using planar illumination of suspended tracer particles. The effects of anastomosis geometry and flow in the proximal artery were investigated in models with anastomosis angles of 15, 30 or 45 degrees. The flow patterns in steady flow were highly three-dimensional and comprised two helical vortices in the distal artery, a recirculation vortex in the occluded proximal arterial segment and a stagnation point on the floor of the artery. Flow separation was observed at the toe of the anastomosis in the 30 and 45 degree models only. A second separation point was also found on the near wall of the 30 degree models at higher flow rates. Downstream flow in the proximal artery reduced and even eliminated the flow recirculation at the heel of the anastomosis, while upstream flow resulted in a captive vortex at the heel and flow reversal at the toe. In pulsatile flow, the secondary flow components in the distal artery became more pronounced during flow deceleration, particularly at higher Reynolds numbers. Significant flow reversal was observed at the toe of the anastomosis and this extended several vessel diameters along the near wall of the artery and upstream into the hood of the graft. The floor of the artery was subjected to a continually varying shear rate caused by the movement of the stagnation point during the pulsatile cycle. The results are in agreement with the observation that intimal hyperplasia occurs in regions of flow separation at the toe and the heel, and flow stagnation on the floor of the anastomosis.

The elastic properties of a polyurethane arterial prosthesis.

The relationship between the mechanical properties of a fibrous polyurethane arterial prosthesis and the graft manufacturing process variables was studied from uniaxial tensile tests. A non-linear model was used to characterize the cylindrical elastic properties. Experiments on cylindrical segments were carried out to determine the constitutive constants and to assess the applicability of the model to the polyurethane graft. The compliance of 4 mm internal diameter grafts with various wall-thicknesses was predicted. The results were used to produce grafts with compliance matched to that of the carotid and femoral arteries.

Arterial steal phenomenon in femoro-tibial bypass with arterio-venous shunt.

Arterio-venous shunts are sometimes constructed at the distal anastomosis of femoro-tibial bypass grafts in order to increase blood flow velocity within the graft. However, the use of such a shunt may "steal' blood from an already ischaemic distal arterial bed. The aim of this study was to determine the conditions under which this might happen. Experiments were carried out on an in vitro model of the femoro-tibial bypass under steady flow conditions. The simple resistance model of Hyman and Brewer (J. Biomechanics 13, 469-675, 1980), modified to take into account the nonlinear pressure flow relationship through a stenosis, was used to interpret experimental data. Good agreement was obtained between measured and calculated steal.

Flow patterns in the radiocephalic arteriovenous fistula: an in vitro study.

A significant number of late failures of arteriovenous fistulae for haemodialysis access are related to the progression of intimal hyperplasia. Although the aetiology of this process is still unknown, the geometry of the fistula and the local haemodynamics are thought to be contributory factors. An in-vitro study was carried out to investigate the local haemodynamics in a model of a Cimino-Brescia arteriovenous (AV) fistula with a 30 degrees anastomotic angle and vein-to-artery diameter ratio of 1.6. Flow patterns were obtained by planar illumination of micro-particles suspended in the fluid. Steady and pulsatile flow studies were performed over a range of flow conditions corresponding to those recorded in patients. Quantitative measurements of wall shear stress and turbulence were made using laser Doppler anemometry. The flow structures in pulsatile flow were similar to those seen in steady flow with no significant qualitative changes over the cardiac cycle. This was probably the result of the low pulsatility index of the flow waveform in AV fistulae. Turbulence was the dominant feature in the vein, with relative turbulence intensity > 0.5 within 10 mm of the suture line decreasing to a relatively constant value of about 0.10-0.15 between 40 and 70 mm from the suture line. Peak and mean Reynolds shear stress of 15 and 20 N/m2, respectively, were recorded at the suture line. On the floor of the artery, peak values of temporal mean and oscillating wall shear stress of 9.22 and 29.8 N/m2, respectively. In the vein, both mean and oscillating wall shear stress decreased with distance from the anastomosis.

Characterisation of vortex shedding in vascular anastomosis models using pulsed Doppler ultrasound.

Vortex shedding at vascular anastomoses were investigated in vitro using a 20 MHz pulsed-wave Doppler velocimeter. Centreline velocity measurements were made at various axial distances in simplified polyurethane models of proximal and distal end-to-side anastomoses of angles 15, 30, 45, 60 and 80 degrees using pulsatile flow waveforms similar to those in femoropopliteal bypass grafts. The in-phase and quadrature Doppler signals were recorded and the maximum frequency waveform, averaged over 64 cycles, was obtained using short-time Fourier transform. A fourth-order Butterworth low-pass filter was employed to separate the vortex velocity signal from the convective velocity. The vortex signal envelope was calculated using a Hilbert transform method and the vortex amplitude was taken as the maximum of this envelope. The results show that higher vortex amplitude were found in the proximal anastomoses and under resting flow conditions. Although the vortex amplitudes generally increased with angles of anastomosis, they were found to be higher in the 60 degrees than in the 80 degrees proximal anastomosis. The vortex structures were investigated using spectrograms and these show prominent features at 40-50 Hz indicative of the short-duration oscillatory signals during the decelerative phase of systole expected from the passage of vortices. The study indicates that flow disturbances due to vortex shedding may be a common feature in femoropopliteal bypass grafts.

Outflow distribution at the distal anastomosis of infrainguinal bypass grafts.

Outflow distribution at the distal anastomosis of infrainguinal bypass grafts remains unquantified in vivo, but is likely to influence flow patterns and haemodynamics, thereby impacting upon graft patency. This study measured the ratio of distal to proximal outflow in 30 patients undergoing infrainguinal bypass for lower limb ischaemia, using a flow probe and a transit-time ultrasonic flow meter. The mean outflow distribution was approximately 75% distal to 25% proximal, with above knee anastomoses having a greater proportion of distal flow (84%) compared to below knee grafts (73%). These in vivo flow characteristics differ significantly from those used in theoretical models studying flow phenomena (50:50 and/or 100:0), and should be incorporated into future research.

The continuous measurement of milk intake at a feed in breast-fed babies.

A method for the continuous measurement of milk intake during a breast-feed is described. A miniature Doppler ultrasound flow transducer, located in the tip of a latex nipple shield, is interposed between mother and baby during feeding. Preliminary results indicate the scope and current limitations of the method in terms of both populations and individual mother/infant pairs. An initial analysis of individual feeds indicates that two factors may contribute to the curtailment of intake during a feed from one breast: a progressive reduction in intake volume per suck, and/or an increase in the proportion of time spent pausing between bursts of sucking.