VSGBI abstracts

BJS Prize Session The following abstracts are from papers presented at the 48th annual scientific meeting of the Vascular Society of Great Britain and Ireland, held in Manchester from 27 to 29 November 2013. The BJS Prize was won by Philip Stather of Leicester. Ascorbic acid ameliorates renal injury in a murine model of contrast-induced nephropathy K. E. Rollins1 , A. Noorani1 , L. Janeckova2 , T. Jones2 , M. Griffiths3 , M. Baker2 , J. R. Boyle1

Possession of a lysine allele at position 407 in α2AP was negatively associated with AAA, and appears protective against their development. These data indicate that the regulation of plasmin activity (through α2AP), rather than plasmin generation (TAFI, tPA), may play a role in AAA.

1 Cambridge Vascular Unit, UK; 2 Antitope Ltd, UK; 3 Department of Histopathology,

Cambridge University Hospitals, UK Contrast induced nephropathy (CIN) is the commonest cause of iatrogenic renal injury and its incidence has increased with the advent of complex endovascular procedures. Evidence suggests that ascorbic acid (Vitamin C) has a nephroprotective effect in percutaneous coronary interventions. The aim of this study was to evaluate the therapeutic effect of ascorbic acid in an in vivo murine model of CIN. Twenty-four mice were divided into 4 groups. Three groups were exposed to high doses of contrast media (omnipaque) in a well-established model of CIN and then treated with low or high dose ascorbic acid (AA) or placebo (saline). Urine was analysed for markers of renal injury. Mice were sacrificed and kidneys analysed by immunohistochemistry for caspase-3, NGAL (neutrophil gelatinase-associated lipocalin) and TUNEL to assess apoptosis. Kidney lysates were analysed by ELISA. Urinary NGAL:creatinine ratio was significantly lower with 44% and 62% (204.3 α g/mmol versus 533.6 α g/mmol p < 0.05) reduction in the low and high dose AA groups respectively at 48-hours. Furthermore a reduction of 58% was demonstrated at 96-hours in the high dose group (280 α g/mmol versus 680.7 α g/mmol p < 0.05). Immunohistochemistry for markers of early apoptosis showed a decrease in TUNEL and caspase-3 expression in both AA groups. NGAL ELISA analysis of kidney lysates also demonstrated a 57% (12,576 ng/ml versus 29,393 ng/ml) reduction after low dose AA treatment. Ascorbic acid ameliorated the contrasted induced renal injury in this murine model of CIN. Further work is required to establish whether ascorbic acid can reduce the incidence of CIN in humans undergoing endovascular procedures.

Stem cells in nonreconstructable CLI-a myth or reality? N. Pathak, S. Singh, V. S. Bedi, V. Anand, R. P. S. Gambhir Military Hospital Amritsar, India To induce therapeutic angiogenesis by injecting autologous peripheral stem cells in non reconstructable CLI. Grade III or IV Fontaine PAOD patients with non-reconstructable disease on angiography were consented to receive G-CSF 300ug bd. CD34+ cell counts were taken every day from 3rd day till 5th day. The day an increase of ratio to >0.10 was seen, G-CSF treatment was stopped and peripheral blood stem cells were harvested. 40–60 ml of cell suspension prepared was then injected into the ishaemic muscle. 20 patients with mean age of 49.7 years (32–65 yrs), with DSA proven, non-reconstructable, infragenicular occlusive disease, underwent successful harvesting and treatment in a two year period. The concentration of total viable mononuclear cells in final suspension was 3.873 ±1.849 × 108/ml. At 6 months no major amputation, 3 minor amputations were done and 9 of the 12 ulcers had healed. The ischaemic rest pain on numerical rating scale decreased significantly from a mean of 7.5 at baseline to 3.5 at 6 months(Paired samples t-test, p < 0.001). The mean preprocedural ABI increased from 0.47 to 0.73 at 6 months (p < 0.001). Baseline mean TcPO2 increased from 27 mm Hg to 35 mm Hg at the end of 6 months (p < 0.001). New collateral vessel development at 6 months was seen in 20% of patients. Only 3 patients had minor adverse events. Intramuscular application of EPC’s after G-CSF stimulation is safe and feasible and improves clinical outcome as measured by ABI, TcPO2, ulcer healing, angiographic scores, and pain reduction.

Fibrinolysis protein polymorphisms and abdominal aortic aneurysms K. I. Bridge1,2 , F. Macrae1 , A. Johnson1 , R. A. S. Ariens1 , D. J. A. Scott1,2 1 Department of Diabetes and Cardiovascular Research, University of Leeds, UK; 2 Leeds Vascular Institute, Leeds Teaching Hospital NHS Trust, UK

Abdominal Aortic Aneurysm (AAA) involves dilatation of the abdominal aorta, with a natural history of expansion and eventual rupture. We have shown that AAA patients form denser clots with smaller pores, which are more resistant to fibrinolysis. The aim of this study was to determine whether functional polymorphisms of the fibrinolytic system play a role in the development of AAA. Caucasian subjects > 55 years (602 AAA patients and 490 controls) were genotyped for four polymorphisms (alpha-2 antiplasmin α2AP Arg6Trp and Arg407Lys, Thrombin-activatable fibrinolysis inhibitor TAFI Thr325Ile and tissue plasminogen activator tPA 7351C→T). DNA was extracted from blood, and genotype identified using real time PCR. Data was analysed using SPSSv20. Genotypes across the study population were in Hardy-Weinberg Equilibrium. The TAFI Thr325Ile and the tPA 7351C→T polymorphisms were not associated with AAA. The two α2AP polymorphisms, Arg6Trp and Arg407Lys appeared to be in linkage disequilibrium (P < 0.0001), and possession of the mutant lysine allele negatively associated with AAA (odds ratio 0.833, CI95 0.7-0.991, P = 0.040). A proportion of both AAA patients (8.3%) and controls (8.6%) had a positive family history of AAA, but there was no correlation between this and any of the polymorphisms investigated.

 2014 The Authors BJS  2014 BJS Society Ltd

An inflammatory single nucleotide polymorphism is related with post-EVAR aneurysm neck growth A. Saratzis1 , S. Jacqueline1 , C. Johnson1 , N. Melas2 , N. Saratzis2 , G. D. Kitas1 1 Department of Research and Development, Russells Hall Hospital, Dudley, West Midlands, UK; 2 Papageorgiou General Hospital, Thessaloniki, Greece

Neck dilatation following endovascular aneurysm repair (EVAR) may lead to endoleak or migration. It is unclear whether it is related to pre-existent structural vessel-wall abnormalities or haemodynamic forces related to the abdominal aortic aneurysm (AAA) and the endovascular device. The aim of this study was to assess whether functional inflammatory and proteolytic polymorphisms are associated with neck dilatation after EVAR. Eight functional single nucleotide polymorphisms (SNPs) previously linked with AAA presence or aortic inflammation were analysed in patients undergoing elective EVAR for an infrarenal AAA. Patients underwent computed tomography (CT-angiogram) of their aorta pre-operatively, at 1, 3, and 12 months after EVAR. A total of 323 patients (mean age: 69 ± 8 years, mean AAA diameter: 6.1 ± 1.2 cm, mean neck diameter 27.3 ± 4.5 mm) had complete imaging and genetic data. At 12 months, the net increase in neck diameter was 2.06 mm relative to the first post-operative CT; 28% enlarged >2.5 mm. The triallelic rs3091244

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VSGBI abstracts

C-reactive protein (CRP) SNP was associated with significantly higher growth rate at 12 months for those who had an A or T allele (p = 0.028), even after adjusting for endoleak and cardiovascular risk-factors (odds ratio: 1.54, 95% confidence interval: 1.08-1.62, p = 0.014). The minor alleles (A and T) were also associated with higher CRP levels (p < 0.001) pre-operatively. None of the other SNPs (ACE, MTHFR, eNOS, MMP-3, MMP-9, MMP-12, PAF) were associated with neck growth. The rs3091244 CRP SNP was related with neck growth at 12 months in this analysis, suggesting that the phenomenon may be partly due to an inherent inflammatory process of the aortic wall.

Blood oxygenation level dependent MRI: A novel perfusion imaging strategy for the ischaemic limb A. Bajwa1 , R. Wesolowski2 , A. Patel1 , P. Saha1 , O. Lyons1 , A. Smith1 , E. Nagel2 , B. Modarai1 1 Academic Department of Surgery, Cardiovascular Division, Kings College London,

Biomedical Research Centre at Guy’s & St Thomas’ NHS Foundation Trust and Kings College London, UK; 2 Department of Cardiovascular Imaging, Division of Imaging Sciences and Medical Engineering, Kings College London, Biomedical Research Centre at Guy’s & St Thomas’ NHS Foundation Trust and Kings College London, UK Ankle-brachial pressure index and transcutaneous oxygen measurements are poor surrogates for quantifying oxygenation/perfusion in the lower limb. We aimed to optimise non-contrast magnetic resonance imaging (MRI) sequences, originally developed for assessing myocardial perfusion, to measure leg perfusion. Six patients with critical limb ischaemia (CLI), 5 healthy volunteers and 3 age-matched controls underwent blood oxygenation level dependent (BOLD) MRI of the calf. A thigh cuff was inflated to suprasystolic pressure for 5 mins then released to provoke reactive hyperaemia during the scan. The time to peak (TTP) T2-star signal and the rate of increase in signal after decuffing (gradient) was analysed for the anterior muscles and soleus. TTP was higher (ANOVA, p < 0.001) in the ischaemic leg of CLI patients (98.10s, CI:78.96-117.24) compared with the contralateral (non-ischaemic) limb (53.10s, CI:44.57-61.63), limbs of volunteers (33.09s, CI:29.60-36.58) and agematched controls (52.00s, CI:39.30-64.70). The gradient was lower (ANOVA, p < 0.001) in the ischaemic leg (0.93, CI:0.44-1.43) compared with the nonischaemic leg (1.57, CI:1.15-2.00) and limbs of volunteers (3.20, CI: 2.70-3.70) and age-matched controls (2.54, CI:2.21-2.87). The TTP and gradient remained significantly different between the ischaemic legs, age-matched controls and volunteers after post-hoc analysis (Tukey HSD). All values are means with 95% Confidence Intervals. BOLD MRI discriminates between ischaemic and normoxic muscle and can be used to delineate poorly perfused areas in the limb. This may guide interventions and provide an objective means of quantifying improvements immediately after treatment. BOLD MRI could supersede current limb imaging methods, such as CT angiography, which only provide anatomical data.

Computational Fluid Dynamic (CFD) analysis of the distraction forces experienced by stent-grafts following fEVAR S. M. Jones1 , R. J. Poole2 , T. V. How2 , R. L. Williams2 , R. G. McWilliams1 , J. A. Brennan1 , S. R. Vallabhaneni1 , R. K. Fisher1 1 Royal Liverpool and Broadgreen University Hospitals NHS Trust, UK; 2 University

of Liverpool, UK Pull-out studies have demonstrated fixation forces of 11.5N for the proximal body of fenestrated stent-grafts, 6.5N for the distal body and 9.5N for the

 2014 The Authors BJS  2014 BJS Society Ltd

limb extension. These forces oppose haemodynamic distraction forces (DF) experienced by the components and resist migration. This study investigated DF acting upon individual stent-graft components following fEVAR and the influence of morphology. Computer models of 54 fEVARs were constructed from the 1st post-operative CT scan (ScanIP software). A CFD package was used to model flow at peak systole and determine DF experienced by the stent-graft components. Boundary conditions were representative of a hypertensive patient at rest. The correlation of DF with morphological features was analysed. Fifty four fEVARs comprised 54 proximal bodies (PB), 52 distal bodies (DB) and 67 limb extensions (LE). Median distraction force for PB components was 4.8 N (range 1.3-15.7 N), for DB 5.6 N (1.0-8.0 N) and for LE 1.7N (0.6-8.4 N). In 2 proximal and 11 distal bodies distraction force exceeded the respective fixation forces. Inlet cross-sectional area of PB and DB components correlated strongly with the magnitude of distraction force (Spearman’s rho = 0.885 p < 0.001). Limb extension outlet cross-sectional area showed equally strong positive correlation with distraction force. In addition, angulation of >45◦ was associated with significantly higher distraction force (p = 0.001). This study characterises the distraction forces experienced by individual components of a fenestrated repair, of which 8% exceeded fixation force and may potentially cause graft related complications. The main determinants of distraction force were vessel cross-sectional area and angulation of the iliac limb extension.

Post-transcriptional dysregulation of extracellular matrix modifying genes in patients with Abdominal Aortic Aneurysms P. W. Stather1 , N. Sylvius2 , D. A. Sidloff1 , J. B. Wild1 , A. Verissimo1 , N. Dattani1 , H. Z. Butt1 , E. Choke1 , R. D. Sayers1 , M. J. Bown1 1 Department of Cardiovascular Sciences, University of Leicester, UK; 2 University

of Leicester, UK MicroRNAs are crucial in the regulation of cardiovascular disease and represent novel therapeutic strategies to decrease abdominal aortic aneurysm (AAA) expansion. The aim of this study was to identify circulating microRNAs associated with AAA and explore their functional effects. 754 microRNAs in whole blood samples from 15 AAA and 10 controls were quantified using qRT-PCR. Significant microRNAs were validated in 200 patients (40 each screened controls, peripheral arterial disease (PAD), small AAA (30-54 mm), large AAA (>55 mm), post-operative) peripheral blood and plasma samples using digital PCR. 29 differentially expressed microRNAs were identified in the discovery study. Validation study analysis revealed let-7e (fold change −1.82; P = 0.001), miR-15a (FC −2.22; P < 0.001), and miR-196b (FC −2.27; P < 0.001) were downregulated in peripheral blood from AAA patients, and miR-411 (FC −5.90; P = 0.001) was upregulated. Mir-196b was also downregulated in plasma from the same individuals (FC −3.75; P = 0.029). Neither exclusion of the aneurysm nor aneurysm size altered miRNA profiles. The same miRNAs were also similarly differentially expressed in patients with PAD. Target prediction analysis using MirWalk revealed that the AAA associated miRNAs were all regulators of AAA related genes; let-7e (COL1A1, COL1A2, COL3A1, MTHFR, MMP1); miR-15a (DAB2IP, MMP3, MTHFR); miR-196b (COL1A1, COL1A2, COL3A1); miR-411 (MMP12, MMP13, MTHFR). Circulating levels of let-7e, miR-15a, miR-196b and miR-411 are differentially expressed in patients with AAA compared to healthy controls, with miR-196b replicated in plasma. Regulation of these miRNAs and their target genes represents a new therapeutic pathway to decrease AAA progression.


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Abstracts of the 48th Annual Scientific Meeting of the Vascular Society of Great Britain and Ireland, 27–29 November 2013.

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