Peter Arno Stonebridge

Lipid-lowering and skin vascular responses in patients with hypercholesterolaemia and peripheral arterial obstructive disease

Elevated blood cholesterol is a major risk factor for atherosclerosis. Recent studies show that lowering cholesterol reduces the risk of vascular disease, but the precise mechanisms for vascular improvement are not fully understood. Furthermore, it is not known whether the beneficial effects of cholesterol lowering extend to the skin microvasculature. In this unrandomized, open design study, we used iontophoresis and laser Doppler flowmetry to examine forearm skin perfusion in hypercholesterolaemic patients with PAOD before and after cholesterol-lowering therapy with fluvastatin. Endothelium-dependent and -independent vasodilatation were measured following skin iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP), respectively. Before cholesterol-lowering, vascular responses to ACh and SNP were reduced significantly in patients compared with responses in control subjects (p, 0.001 and p, 0.05, ANOVA, respectively). Fluvastatin therapy (40 mg/day) for 24 weeks significantly reduced total cholesterol (7.3 6 0.3 to 6.0 6 0.2 mmol/l, p, 0.001) and LDL cholesterol (5.4 6 0.5 to 4.2 6 0.4 mmol/l, p, 0.01). Vasodilatation to SNP was significantly improved at week 24 (p, 0.05). In patients with hypercholesterolaemia and PAOD, cholesterol-lowering with statin therapy significantly improved endothelium-independent vascular responses to SNP in skin microvessels. The application of the non-invasive techniques of iontophoresis and laser Doppler flowmetry may provide useful markers for the assessment of microvascular function in this group of patients.

The prevalence of treatable left ventricular systolic dysfunction in patients who present with noncardiac vascular episodes: A case-control study☆

OBJECTIVES We sought to determine the prevalence of treatable left ventricular (LV) systolic dysfunction (LVSD) in patients who present with their first noncardiac vascular episode. BACKGROUND Screening for LV dysfunction in patients who present with their first stroke (cerebrovascular accident), their first transient ischemic attack (TIA) or their first manifestation of peripheral vascular disease (PVD) may represent a golden opportunity to identify treatable LV dysfunction, and so their known high incidence of sudden cardiac death may be reduced. METHODS Participating in this study were 522 (75%) of 700 consecutive patients (302 patients with stroke, TIA or PVD and 220 age- and gender-matched control subjects). Each underwent a full clinical assessment, 12-lead electrocardiography and two-dimensional echocardiography. Left ventricular dysfunction was defined as LV ejection fraction < or = 40%. RESULTS Seventy-two (28%) patients with vascular disease and 11 (5.5%) control subjects were found to have LVSD. Twenty-six (28%) stroke patients, 22 (26%) patients with TIA and 24 (31%) patients with PVD had LVSD. Left ventricular systolic dysfunction was symptomatic in 44% of patients and in 35% of control subjects. CONCLUSIONS Left ventricular systolic dysfunction is five times more common among patients with stroke, TIA and PVD than among age- and gender-matched control subjects. Asymptomatic LVSD is more common than symptomatic LVSD in these patients. These findings suggest that routine screening of all patients with noncardiac vascular episodes for LVSD should now be considered. Future studies should investigate whether identifying and treating LVSD in these patients would reduce their known high rate of cardiac death.

Spiral Laminar Flow Prosthetic Bypass Graft: Medium-Term Results From a First-In-Man Structured Registry Study

BACKGROUND A number of surgical strategies and graft enhancements have been trialled to improve the performance of prosthetic grafts. Neointimal hyperplasia may, in part, be a normal cellular response to an abnormal (turbulent) flow environment. This first-in-many study assesses the safety and medium-term patency performance of a new graft designed to induce stable laminar flow through the distal anastomosis. METHOD Forty patients who required an infrainguinal bypass graft were recruited/registered from a number of centers in Belgium and The Netherlands. Thirty-nine received a Spiral Laminar Flow graft as part of a standard treatment protocol (23 above-the-knee and 16 below-the-knee bypasses). Kaplan-Meier analyses were used to calculate primary and secondary patency rates. RESULTS The 12-, 24-, and 30-month primary patency rates were 86%, 81%, and 81% for above-the-knee bypasses and 73%, 57%, and 57% for below-the-knee bypasses, respectively. In the case of secondary patency rates, numbers were unchanged for above-the-knee bypasses and were 86%, 64%, and 64%, respectively, for below-the-knee bypasses. There were no amputations in the study population. CONCLUSION This first-in-man series shows potential for the idea of spiral flow-enhanced prosthetic grafts. As always, randomized studies are required to explore the role of different enhanced prosthetic grafts.

Decrease in P-selectin levels in patients with hypercholesterolaemia and peripheral arterial occlusive disease after lipid-lowering treatment.

At sites of thrombosis and vascular injury, interactions occur among platelets, leucocytes and endothelial cells. Patients with peripheral arterial occlusive disease (PAOD) have been shown to have raised total serum cholesterol and serum triglycerides and increased sP-selectin levels when compared with controls. A total of 31 patients with PAOD and hypercholesterolaemia took part in this three-staged study. Soluble P-selectin (sP-selectin) levels were significantly lowered after 12 weeks of fluvastatin treatment (157.0 ng/ml versus 113.77 ng/ml, p = 0.01), whereas 12 weeks of placebo treatment had no statistically significant effect on sP-selectin levels (150.0 ng/ml versus 139.4 ng/ml). An unpaired t-test almost reached statistical significance (p = 0.051) when the levels by which sP-selectin fell after 12 weeks of active or placebo treatment were compared. The placebo group was then put onto long-term, active treatment and sP-selectin levels were significantly lowered by fluvastatin when compared to pre-treatment levels (150.0 ng/ml versus 110.0 ng/ml, p = 0.03). By lowering the levels of P-selectin, fluvastatin may not only attenuate atherosclerotic progression but may also decrease the platelet activation associated with PAOD.

Hemodynamic effects of spiral ePTFE prosthesis compared with standard arteriovenous graft in a carotid to jugular vein porcine model

Introduction The primary patency rate of arteriovenous (AV) grafts is limited by distal venous anastomosis stenosis or occlusion due to intimal hyperplasia associated with distal graft turbulence. The normal blood flow in native arteries is spiral laminar flow. Standard vascular grafts do not produce spiral laminar flow at the distal anastomosis. Vascular grafts which induce a spiral laminar flow distally result in lower turbulence, particularly near the vessel wall. This initial study compares the hemodynamic effects of a spiral flow–-inducing graft and a standard graft in a new AV carotid to jugular vein crossover graft porcine model. Methods Four spiral flow grafts and 4 control grafts were implanted from the carotid artery to the contralateral jugular vein in 4 pigs. Two animals were terminated after 48 hours and 2 at 14 days. Graft patency was assessed by selective catheter digital angiography, and the flow pattern was assessed by intraoperative flow probe and color Doppler ultrasound (CDU) measurements. The spiral grafts were also assessed at enhanced flow rates using an external roller pump to simulate increased flow rates that may occur during dialysis using a standard dialysis needle cannulation. The method increased the flow rate through the graft by 660 ml/min. The graft distal anastomotic appearances were evaluated by explant histopathology. Results All grafts were patent at explantation with no complications. All anastomoses were found to be wide open and showed no significant angiographic stenosis at the distal anastomosis in both spiral and control grafts. CDU examinations showed a spiral flow pattern in the spiral graft and double helix pattern in the control graft. No gross histopathological effects were seen in either spiral or control grafts. Conclusion This porcine model is robust and allows hemodynamic flow assessment up to 14 days postimplantation. The spiral flow–-inducing grafts produced and maintained spiral flow at baseline and enhanced flow rates during dialysis needle cannulation, whereas control grafts did not produce spiral flow through the distal anastomosis. There was no deleterious effect of the spiral flow–-inducing graft on macroscopic and histological examination. The reducing effect of spiral flow on intima hyperplasia formation will be the subject of further study using the same AV graft model at a longer period of implantation.

Secondary Flow in Peripheral Vascular Prosthetic Grafts Using Vector Doppler Imaging

Prosthetic grafts are used for the treatment of peripheral arterial disease. Re-stenosis in the distal anastomosis of these grafts is a common reason for graft occlusion. The role of local hemodynamics in development of neo-intimal hyperplasia is well known. A new graft design has been proposed for the induction of optimized spiral flow in the host vessel. The secondary flow motions induced by this graft were compared with those of a control device. Both types of grafts were connected with vessel mimic and positioned in ultrasound flow phantoms with identical geometry. Constant flow rates were applied. Data collected in the cross-sectional view distal from the graft outflow and dual-beam vector Doppler was applied to create 2-D velocity maps. A single-spiral flow pattern was found for the flow-modified graft, and double or triple spirals for the control graft. In-plane maximum velocity was greater for the flow-modified graft than for the control device.

Left ventricular hypertrophy is present in one-half of newly-diagnosed peripheral arterial disease patients.

Objectives Peripheral arterial disease (PAD) patients are at high risk of cardiac death. Coincidental but silent coronary disease is obviously a major contributor but left ventricular hypertrophy (LVH) could be a second major contributor. Methods To investigate whether LVH could really be making a large contribution to cardiac death in PAD, we assessed the prevalence of LVH when PAD was first diagnosed. Results The prevalence of echo LVH when left ventricular mass was indexed to body surface area was 50%. Although office blood pressure and 24-h blood pressure were both significantly higher in those with LVH, in clinical practice, a contemporaneous blood pressure measurement (office or 24 h) at the time of PAD diagnosis would only partially identify those with LVH. For example, an office blood pressure cut-off of < 140/90 mmHg was found in 27% of all LVH cases and a 24-h blood pressure cut-off of < 125/80 mmHg was found in 24% of all LVH cases. Conclusion In conclusion, there is already a high prevalence of LVH in patients at first diagnosis of PAD. LVH is therefore common enough in PAD patients to potentially make a major contribution to cardiac death, which means that future research should now investigate whether screening for and regressing LVH when present would actually reduce cardiac deaths over and above merely achieving target blood pressure.

Comparison of vortical structures induced by arteriovenous grafts using vector Doppler ultrasound.

Arteriovenous prosthetic grafts are used in hemodialysis. Stenosis in the venous anastomosis is the main cause of occlusion and the role of local hemodynamics in this is considered significant. A new spiral graft design has been proposed to stabilize the flow phenomena in the host vein. Cross-flow vortical structures in the outflow of this graft were compared with those from a control device. Both grafts were integrated in identical in-house ultrasound-compatible flow phantoms with realistic surgical configurations. Constant flow rates were applied. In-plane 2-D velocity and vorticity mapping was developed using a vector Doppler technique. One or two vortices were detected for the spiral graft and two to four for the control, along with reduced stagnation points for the former. The in-plane peak velocity and circulation were calculated and found to be greater for the spiral device, implying increased in-plane mixing, which is believed to inhibit thrombosis and neo-intimal hyperplasia.

An animal paired crossover ePTFE arteriovenous graft model

PurposePreviously, we developed a porcine model for Arterio Venous Graft (AVG) failure to allow assessment of new access strategies. This model was limited concerning graft length. In the present technical report, we describe a modification of our model allowing the assessment of long AVGs.TechniqueIn 4 pigs, AVGs of 15 cm length were created bilaterally in a cross-over fashion between the carotid artery and the contralateral jugular vein. Two days (2 pigs) and two weeks (2 pigs) after AV shunting, graft patency was evaluated by angiography, showing all four grafts to be patent, with no sign of angiographic or macroscopic narrowing at the anastomoses sites.ConclusionsIn this modified pig AVG failure model, implantation of a bilateral cross-over long AVG is a feasible approach. The present model offers a suitable tool to study local interventions or compare various long graft designs aimed at improvement of AVG patency.

Vector doppler imaging and secondary flow patterns in vascular prostheses

Flow patterns created by vascular prostheses designed to induce spiral flow, were compared against standard plain grafts using an in-house ultrasound flow phantom. Color Doppler and vector Doppler imaging were applied to visualize and quantify secondary flow motions distally to the grafts outflow. The flow phantom incorporates a piston pump, blood mimic fluid, vessel mimicking tubing consisting of polyvinyl alcohol, in 9% glycerol solution. Spiral Laminar FlowTM Peripheral Vascular (PV) and Access Vascular (AV) grafts (Vascular Flow Technologies, Dundee, UK) were compared with standard control PV and AV grafts. Steady flow rates up to 720 ml min-1 were applied. Color Doppler cine loops were acquired from the left (8 = 20) and right (8 = -20) projection, with the transducer positioned transverse to the flow direction. The velocity data was subjected to triangulation in order to generate in-plane velocity magnitude and direction maps. Complicated rotational patterns were detected in the connection between the graft and the vessel mimic, with a prevalent single helix for the spiral prostheses and a prevalent double helix for the control devices. A clear single spiral pattern was found distally of the spiral grafts and a double distally of the standard devices. The magnitude of the radial component velocity distally from the PV spiral graft, was found to be significantly higher (p <; 0.05) compared to the control device. This study compared different vascular graft designs in terms of their outflow patterns, using a dual-beam color Doppler mapping.