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Cerebrospinal Fluid Analysis After Endovascular Thoracoabdominal Aneurysm Repair: Disruption of the Blood-spinal Cord Barrier Predicts Permanent Paraplegia

Authors:
apoptosis by Caspase-3 detection. In addition, the expres-
sion of cluster of differentiation 31 (CD-31) and vascular cell
adhesion molecule 1 (VCAM-1) were also investigated by
immunochemistry.
Results: The endothel-dependent maximal vasorelaxation
(R
max
) was improved (nontransplanted-control (nCo): 84
3%, Aspirin (Asp): 42 4%, transplanted- control (Co): 14
2%), the nitro-oxidative stress (Nitrotyrosine-3 positive
area: nCo: 26 2%, Asp: 38 3%, Co: 69 1%) and cell
apoptosis (Caspase-3 positive area: nCo: 20 2%, Asp: 34
3%, Co: 74 3%, TUNEL positive area nCo: 12 2%, Asp:
41 5%, Co: 70 3%) decreased and signicant endothel
protection (CD-31 positive endothelium area: nCo: 87 1%,
Asp: 39 3%, Co: 23 1%, VCAM-1 positive endothelium
area: nCo: 14 2%, Asp: 40 5%, Co: 79 2%) was also
shown in the groups preconditioned with Aspirin.
Conclusion: Orally administered Aspirin showed a marked
improvement of the endothelial function and reduced
structural damage caused by I/R injury in arterial grafts.
Disclosure: Nothing to disclose
O-245 Fluid Shear-stress Increases TRPV4-Expression in
Human Endothelial Cells in an Experimental in Vitro Model
Vascular Biology
Thomas Schmandra
1
, Rita Al Weissi
2
, Kerstin Troidl
2
,
Thomas Schmitz-Rixen
2
1
Rhön-Klinikum Campus Bad Neustadt, Department of Vascular Surgery, Bad
Neustadt, Germany
2
Goethe-University Frankfurt, Department of Vascular and Endovascular
Surgery, Frankfurt, Germany
Introduction: Transient receptor potential cation channel,
subfamily V, member 4 (TRPV4) is a non-selective cation
channel that tunes the function of different tissues including
the vascular endothelium, lung, chondrocytes, and neurons.
In vascular collateral growth regularly seen in induced limb
ischemia TRPV4 expression in endothelial cells is signicantly
increased. As a consequence induction of TRPV4 expression
could be used for augmentation of arteriogenesis. This study
aimed to determine the importance of uid shear-stress on
TRPV4 expression in endothelial cells. To avoid further in-
vestigations in small animal models an in vitro model using
arterial endothelial cells was to be established.
Methods: Human umbilical artery endothelial cells (HUAEC)
were harvested and cultivated on special slides and exposed
to a certain level of uid shear-stress (20 Dyn/cm2) for 0.5,
1, 4, 8, 10, 12, 18 and 24 hours. Messenger RNA (mRNA)
abundance was determined in HUAEC by quantitative real-
time polymerase chain reaction (qRT-PCR) and immuno-
histochemistry in dependency to length of uid shear-stress
exposure.
Results: The establishment and validation of an in vitro
model using cultivated HUAEC to investigate the effect of
uid shear stress on TRPV4 expression was successful. The
extent of endothelial TRPV4 mRNA expression showed a
direct correlation to length of uid shear-stress exposure
with a peak after 8 hours of shear-stress exposure. After 8
hours endothelial mRNA expression was signicantliy
increased in comparison to control endothelial cells without
uid shear-stress stimulation (p¼0.041 in 8h FSS vs. Con-
trol). Fluid shear stress exposure of 10, 12, 18 and 24 hours
showed decreasing TRPV4 mRNA expression in endothelial
cells and no differences to control cells with uid shear-
stress stimulation extending to more than 12 hours.
Conclusion: TRPV4 showed a signicantly increased
expression in uid shear-stress stimulated HUAEC. The
established in vitro model seems suitable to investigate
further impacts on uid shear-stress stimulated HUAEC, e.g.
additional pharmacological TRPV4 activation to enhance
arteriogenesis, as TRPV4 could be a possible candidate for
the development of new therapeutic concepts in chronic
limb ischemia.
Disclosure: Nothing to disclose
O-246 Cerebrospinal Fluid Analysis After Endovascular
Thoracoabdominal Aneurysm Repair: Disruption of the
Blood-spinal Cord Barrier Predicts Permanent Paraplegia
Thoraco-abdominal Aortic Disease
James Kelly
1
, Ashish Patel
1
, Izem Onadem
1
, Said Abisi
2
,
Rachel Bell
2
, Mark Tyrrell
2
, Morad Sallam
2
,
Marwah Salih
1
, Manuel Mayr
1
, Elizabeth Bradbury
1
,
Philippa Warren
1
, Jun Cho
1
, Thomas Booth
1
,
Alberto Smith
1
, Bijan Modarai
1
1
Kings College London, London, United Kingdom
2
Guys and St ThomasHospital, London, United Kingdom
Introduction: Despite modern strategies to minimise spinal
cord ischaemia (SCI) after thoracoabdominal aortic aneu-
rysm (TAAA) repair, this devastating complication remains
unpredictable and is poorly understood. We related tem-
poral changes in the cellular and molecular composition of
cerebrospinal uid (CSF) to neurological outcomes after
TAAA repair with the aim of gaining mechanistic insights
and identifying a biomarker for SCI.
Methods: Patients undergoing TAAA repair (open or
endovascular using branched/fenestrated stent grafts) with
a CSF drain in place were prospectively recruited between
October 2016 and August 2018. CSF was collected pre-
operatively and at 24-hourly intervals until drain removal.
Detailed daily neurological examinations were performed
and the diagnosis of SCI was made by a neurologist blinded
to the study. CSF cell content was characterised by ow
cytometry. The CSF proteome was analysed by tandem-
mass-tag labelled proteomics and principle component
analysis. T2 weighted spinal-cord MRI was used to measure
cord volume by neuro-radiologists blinded to patient
outcomes.
Results: CSF was analysed from 52 patients (age: 70.27
+/-11.4 years; 66% male; Crawford Type I (10.8%) II (29.2%),
III (26.2%), IV (30.8%), V (3.1%); open (n¼9), endovascular
(n¼43). 12 patients, all of whom had undergone endovas-
cular repair, developed SCI with 5 of these remaining
permanently-paraplegic. Demographics, extent of aortic
Abstracts e717
coverage and preoperative CSF content was comparable
between patients with no SCI, those with reversible SCI and
those that remained paraplegic. Permanent paraplegia was
associated with a signicant inltration of CD45
+
leucocytes
into the CSF (P<0.0001). Levels of ADVS-1, an astrocyte
osmoreceptor essential in maintaining blood/spinal cord
barrier integrity, was >7-fold higher in CSF from perma-
nently-paraplegic patients compared with those that
recovered (P¼0.0008). CSF ADVS-1 levels >15ng/ml pre-
dicted permanent paraplegia with a specicity of 100%.
Permanent paraplegics were more likely to have patholog-
ical spinal cord swelling at T11 (1.9 fold greater cord vol-
ume), T12 (2.1 fold greater cord volume) and L1 (2.9 fold
greater cord volume) on T2-weighted MRI when compared
with the other groups (P<0.05 at each level).
Conclusion: The present study is the largest prospective
analysis of CSF in patients undergoing TAAA repair to date.
Our ndings suggest that permanent paraplegia is associ-
ated with shedding of bound ADVS-1 from the parenchymal
cord into CSF and disruption of the blood/spinal-cord bar-
rier, which in turn leads to cord oedema and a leucocyte
inltration. This characteristic CSF signature predicts irre-
versible paraplegia after TAAA repair and identies ADVS-1
as a novel therapeutic target. ADVS-1 inhibition after
ischaemic stroke stabilises the blood/brain barrier, prevents
cerebral oedema and limits cytotoxic brain damage. We are
investigating whether similar modulation of ADVS-1 can
stabilise the blood/spinal cord barrier and prevent perma-
nent paraplegia.
Disclosure: Nothing to disclose
O-247 Comparison of Fenestrated Stentgrafts and Open
Repair for Juxtarenal Aortic Aneurysms Using A Propensity
Score Matching
Abdominal Aortic Diseases
Alia Bizos
1
, Xavier Chaufour
1
, Jean Segal
1
,
Jean Senemaud
2
, Pascal Desgranges
2
,
Florence Canoui-Poitrine
2
, Frederic Cochennec
2
1
Toulouse University Hospital, Toulouse, France
2
Henri Mondor University Hospital, Creteil, France
Introduction: The purpose of this study is to compare the
short- and mid-term results of fenestrated stentgrafts
(FEVAR) and open repair (OR) for juxtarenal aortic aneu-
rysms (JRAA).
Methods: This cohort study was conducted in two tertiary
centers between 2005 and 2017. Preoperative CT scans of
patients who underwent FEVAR for complex abdominal AAA
in both centers were reviewed by two experienced sur-
geons to select JRAA and exclude suprarenal and thor-
acoabdominal aneurysms. JRAA were dened as requiring
suprarenal cross clamping but infrarenal proximal suture if
treated by OR. Patients with JRAA treated by FEVAR were
compared to patients with JRAA treated by OR using a
propensity score matching. Propensity score was calculated
on age, sex, smoking, diabetes, obesity, coronary artery
disease, heart/renal/respiratory failure, ASA score, history
of aortic surgery, aneurysm diameter and center.
Results: Of 277 patients with JRAA, 102 (36,8%) received
FEVAR and 175 (63,2%) received OR. Before propensity
score matching, 30-day, in-hospital, 12 months and 36
months mortality rates were 5,9% / 5,9% / 17,5% / 27,8%
(n¼6/n¼6/n¼17/n¼27) in the FEVAR group and 1,7%/4%/
6,5%/9,4% (n¼3/n¼7/n¼11/n¼16) in the OR group,
respectively.
After propensity score matching, 102 FEVAR patients
(66,7%) and 51 OR patients (33,3%) were included in the
analysis. 30-day and in-hospital mortality rates were 5.9%
(N ¼6) in the FEVAR group vs. 3,9% (N¼2) / 7,8% (N¼4) in
the OR group (p¼0,61 / p¼0,64). The median follow-up
period was 40 months (range: 0,2-112) in the FEVAR group
and 41 months (range: 1-149) in the OR group. During
follow-up, overall mortality at 12 months was similar in
both groups (FEVAR: 17,7% vs. OR: 12 %, p ¼0,31). At 36
months, there was a non-signicant trend towards higher
overall mortality rates in the FEVAR group (27,1% vs. 14,0%,
p¼0,07).
FEVAR- patients experienced signicantly fewer moderate
to severe complications (FEVAR group: n¼19, 18,8%; OR
group: n¼21, 41,2%, Odd Ratio ¼0,32; 95% CI: 0.15-0.71; p
¼0,05), especially renal (18,0% vs. 26,0%; p ¼0,005) and
respiratory (4,9% vs. 17,7%; p ¼0,029). In total, twenty-ve
patients required reintervention (16,4%), with no difference
between the two groups (FEVAR: 16,7% vs. OR: 15,7%, p ¼
0,88). In the FEVAR group, two aortic ruptures occurred
during follow-up. Persistent endoleak was observed in 17
patients (16,7%) in the FEVAR group (3 type IA, 13 type II
and 1 unclassied).
Conclusion: This comparative study did not show a signi-
cant difference in mid-term mortality, although a trend
towards higher mortality rates was observed at 36 months
in the FEVAR group. Moderate to severe complications,
especially renal and respiratory, were more frequent in the
OR group. Propensity score matching mainly selected the
most fragile patients in the OR group. This study highlights
the need for a randomized study to compare FEVAR and OR
for juxtarenal AAA.
Disclosure: Frederic Cochennec is a proctor for Cook MEd-
ical
O-248 Incidence, Time-trends and Sex Differences in
Aortic Dissection: A Population Based 15-year Follow-up of
Swedish Patients
Thoraco-abdominal Aortic Disease
Christian Smedberg
1
, Johnny Steuer
1
, Rebecka Hultgren
2
,
STAR
1
Karolinska Institute, Södersjukhuset, Stockholm, Sweden
2
Karolinska Institute, MMK, Stockholm, Sweden
Introduction: Large population based studies in aortic
dissection are lacking. Moreover, most studies do not
include patients who never reached a hospital. Hence,
e718 Abstracts
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