J. Biomedical Science and Engineering, 2013, 6, 6-13 JBiSE
http://dx.doi.org/10.4236/jbise.2013.612A002 Published Online December 2013 (http://www.scirp.org/journal/jbise/)
Biomechanical aspects of catheter-related
Oren Moshe Rotman*, Dalit Shav, Sagi Raz, Uri Zaretsky, Shmuel Einav
Department of Biomedical Engineering, Tel Aviv University, Tel Aviv, Israel
Email: *orenrotm@post.tau.ac.il
Received 30 September 2013; revised 29 October 2013; accepted 12 November 2013
Copyright © 2013 Oren Moshe Rotman et al. This is an open access article distributed under the Creative Commons Attribution Li-
cense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Short peripheral catheters (SPCs) are the most com-
mon intravenous devices used in medical practice.
Short peripheral catheter thrombophlebitis (SPCT) is
the most frequent complication associated with SPCs,
causing discomfort and usually leading to removal of
the catheter and insertion of a new one at a different
site. The aim of this research was to explore whether
biomechanical factors, in addition to biochemical
factors, also play a role in the formation of thrombo-
phlebitis. Hence, two of the biomechanical aspects of
SPCT were investigated: the physical pressure load
exerted by the SPC on the endothelial monolayer, and
disturbances in the flow patterns due to the SPC.
Endothelial activation was studied by subjecting hu-
man umbilical vein endothelial cells (HUVEC) to a
weight load of SPC pieces and measuring the release
profile of von-Willebrand Factor (vWF) over time,
using ELISA. vWF release was chosen as the measure
for endothelial activation since it was the major com-
ponent of the Weibel-Palade Bodies (WPBs), which
underwent exocytosis by endothelial cells during acti-
vation. Flow patterns were analyzed on a 3D compu-
tational fluid dynamics (CFD) model of a brachio-
cephalic vein with SPC. vWF release profiles were
significantly higher in the HUVECs subjected to the
load, indicating HUVEC activation. CFD simulations
demonstrated a decrease in flow velocities along the
catheter body, between the catheter and the vein, due
to an enlarged boundary layer. Results indicate that
the contact region between the SPC body and the vein
wall can be partially responsible for SPCT develop-
ment, and inflammatory and coagulatory processes
initiated by stimulated endothelial cells may be am-
plified due to disturbed blood flow.
Keywords: Endothelial Activation; vWF;
Thrombophlebitis; Phlebitis; Short Peripheral Catheters;
Infusion; Intravenous Access; CFD
Short peripheral catheters (SPC) are the most widely
used intravenous devices in medical practice today, par-
ticularly in hospitals and intensive care units. The SPC is
commonly inserted into veins of the upper extremities to
administer fluids, medications and blood products, or for
prophylaxis before procedures. Short peripheral catheter
thrombophlebitis (SPCT) is the most frequent complica-
tion associated with SPCs, with prevalence in hospital-
ized patients ranging from 2.6% [1] to 77.5% [2]. This
inflammatory process of the vein wall is characterized by
pain, tenderness, warmth, erythema, swelling, and some-
times palpable thrombosis of the cannulated vein. In the
past, SPCT was thought to be initiated by infection from
the insertion site, but studies of catheter tip cultures sug-
gest it may be mediated or initiated by a noninfectious
inflammatory process [1,3-6]. Moreover, SPCT symp-
toms such as local swelling and erythema on the skin
surface commonly appear along the venous track [7],
making the catheter penetration wound not necessarily
initiate the inflammatory process. These findings led us
to hypothesize that the inflammatory process of SPCT is
initiated by the interaction between the catheter body, the
vein wall, and the blood flow.
SPCT causes discomfort and usually results in re-
moval of the catheter and insertion of a new one at a dif-
ferent site. Repeated episodes can lead to venous access
difficulties and more invasive procedures, such as central
venous catheter placement. This usually results in delay-
ed administration of parenteral medications, lengthened
hospital stay and increased costs [6]. Several mecha-
nisms of SPCT pathogenesis have been suggested, in-
cluding vein wall injury combined with stasis and in-
flammation that lead to thrombosis [8], and sterile in-
flammation caused by chemical irritation of the endothe-
*Corresponding author.
O. M. Rotman et al. / J. Biomedical Science and Engineering 6 (2013) 6-13 7
lium due to the infusate or catheter material [9-11]. De-
spite the numerous studies, the pathogenesis of SPCT
remains unclear.
Endothelial cells, which act as the barrier between
blood and organ tissues, have the capability to regulate
local inflammation and coagulation reactions. Where the
immediate response is needed, such as at sites of vascu-
lar injury, the endothelial cells are activated and support
local recruitment of leukocytes and platelets. This re-
cruitment is mediated by the release of the contents of
Weibel-Palade Bodies (WPBs) [12]. While a variety of
chemical stimulations for WPBs exocytosis are reported
in the literature, information is sparse on the effect of
physical pressure of a foreign body, such as that exerted
by SPCs on endothelial cells.
Flow disturbances are known to affect platelet activa-
tion and coagulation by accumulation of shear stresses in
recirculation regions and jets [13], and in stagnation re-
gions due to insufficient flush of highly potent coagula-
tion substances. Such flow regimens may exist in the
vicinity of the SPC and participate in the inflammatory
and coagulatory processes. To the best of our knowledge,
there are no reports on flow patterns in the context of
The present study is a pioneering work that evaluates
the possible effect of two biomechanical aspects of SPCT
development: 1) physical pressure of the SPC on the vein
wall that irritates and activates the endothelial cells, and
2) flow disturbances in the vicinity of the catheter.
The effect of physical pressure load of SPCs on vein
walls was studied in vitro in cultured endothelial cells.
Flow patterns in a cannulated vein model were examined
using computational flow dynamics (CFD) simulations.
2.1. In Vitro Experiments
Fluorinated ethylene propylene (FEP) 16 gauge (1.3 mm
inner diameter, 1.7 mm outer diameter) short peripheral
infusion catheters (Ven-O-Lit®) were placed over human
umbilical vein endothelial cells (HUVEC). Chemical
reactions of the cells to the catheter material were
avoided by employing only genuine infusion catheter
material. The catheters were cut into 1 cm long pieces,
into which 0.7 cm long stainless steel pins were inserted
to prevent the catheter pieces from floating in the me-
dium (Figure 1), forming weights of approximately 75
mg each. This weight was chosen after banding similar
SPC units on digital scales for up to 30˚, an angle that
represents the entrance orientation of the SPC into the
vein. Each of these weights exerted a physical pressure
load of approximately 67 Pa (0.5 mmHg), estimated by
dividing the weight by the contact surface area. Fourteen
Figure 1. Catheter and stainless steel pieces forming load on
HUVEC in a 12-well plate.
weights were then placed over a monolayer of HUVEC
in each well of a 12-well plate, in a static flow environ-
ment, with a confluency of more than 95%. The HU-
VEC samples were divided into two groups of 3 samples
each: the test group, which was subjected to the weight
load, and a control group. The two groups were sampled
simultaneously. For statistical purposes, the in vitro pro-
tocol was repeated twice in a non-dependent fashion,
each time using a different cell passage. HUVEC activa-
tion was measured by quantification of von-Willebrand
Factor (vWF) release, which is the major component of
the WPBs and responsible for platelet adhesion to stimu-
lated endothelial cells [12]. Increased vWF release over
time compared with the control group will indicate WPB
exocytosis—evidence of the increased HUVEC active-
tion that promotes both inflammatory and coagulatory
responses. vWF release was chosen over other compo-
nents of the WPBs because it is abundant and therefore
easy to detect.
2.1.1. Cell Culture
HUVEC (Lonza) were grown in MCBD-131 medium
supplemented with 5% foetal bovine serum (FBS), 2 mM
L-glutamine, 100 U/ml penicillin, and 0.1 mg/ml strep-
tomycin (Biological Industries Beit Haemek, Israel), 2
ng/ml insulin, 0.5 ng/ml epithelial growth factor (Sigma
Aldrich), 2 ng/ml basic-fibroblasts growth factor (bFGF)
(PeproTech, Inc., USA) and 1 μg/ml hydrocortisone
(Sigma Aldrich) cultured at 37˚C, 5% CO2, in a humidi-
fier incubator. Cells from passages 5 - 10 were used. Cell
morphology and confluence were inspected with a Nikon
eclipse TS100 phase inverted microscope and captured
with a Nikon Coolpix 4500 digital camera.
2.1.2. vWF Measur em ent
Cells were seeded at near confluence density of 20,000
cells/cm2 on a 0.1% gelatin (Sigma Aldrich) coated 12-
well plate. When the cells reached 100% confluence, the
medium was replaced and the weights were placed on the
cells. Medium samples were collected and kept at 20˚C
until analyzed. During incubation the cells were kept in a
Copyright © 2013 SciRes. OPEN ACCESS
O. M. Rotman et al. / J. Biomedical Science and Engineering 6 (2013) 6-13
humidifier incubator at 37˚C and 5% CO2. Samples were
taken from the wells of both groups at four different
times: at the beginning of the experiment (t = 0), and
after 20, 40 and 60 minutes. Sixty minutes was found to
be sufficient for this setup after several trials with dif-
ferent time scales, as elaborated in the Discussion sec-
tion. Quantification of vWF was done using Assay-Max
ELISA kit (AssayPro). Briefly, samples were incubated
for 2 hours using a 96-well microplate coated with
murine monoclonal antibody against vWF, after which
the samples were removed and the wells were incubated
for 60 minutes with biotinylated vWF antibody for an-
other 30 minutes with streptavidin-peroxidase conjugate.
The plate was then incubated for 10 minutes with a stabi-
lized peroxidase chromogen substrate, after which a stop
solution (containing 0.5 N hydrochloric acid) was added
to the chromogen solution. The plate was read at 450 nm
by a spectrophotometer (SpectraMax 340PC384, Mo-
lecular Devices Corp., Sunnyvale CA, USA). All incuba-
tions were performed at 37˚C. The wells were washed 5
times between each step using the wash buffer supplied
in the kit. For each procedure, a calibration curve was
calculated using a human vWF standard protein provided
in the kit.
2.1.3. Statistical Analysis
Statistical analysis was performed by ANOVA with re-
peated measures (over time) with covariance structure of
compound symmetry, using SPSS software (SPSS Inc.),
and using the vWF concentration results as input. Sig-
nificance level was considered as p < 0.05.
2.2. Numerical Simulations
2.2.1. Go v ern ing Equa tions
The equations governing continuity (Eq.1) and momen-
tum (Eq.2) for incompressible, viscous and laminar
blood flow were:
0U (1)
  (2)
where U is the velocity vector, P is the static pressure, ρ
is the fluid density, and υ is the kinematic viscosity.
2.2.2. Boundary Conditions
Cephalic vein flow rate is normally 28 ml/min for a vein
diameter of 2.3 mm [14]. In order to keep the Reynolds
number (Re) in our enlarged model of 5 mm diameter
similar to its physiological value, the flow rate was ad-
justed to 60 ml/min (Re = 73). The effect of flow of three
additional flow rates was examined: 28 ml/min (Re = 34),
45 ml/min (Re = 55), and 75 ml/min (Re = 91). The flow
rates were applied to the vein by setting a constant aver-
age velocity at the vein inlet (2.38 cm/s, 3.87 cm/s, 5.1
cm/s, and 6.38 cm/s for flow of 28 ml/min, 45 ml/min,
60 ml/min, and 75 ml/min, respectively). Volume out-
flow condition was set at the vein outlet, meaning that all
the volume of flow in the model was drained through the
outlet surface. Symmetry condition was applied to the
model symmetry plane, such that the velocity gradients
across this plane were equal to zero. No slip condition
was defined at any of the interfaces between the blood
and the catheter or vein walls. The fluid properties were
set as whole blood, with density of ρ = 1060 Kg/m3, and
dynamic viscosity of µ = 3.5 mPa·s.
2.2.3. Compu t ational Method
The governing equations (Eqs.1 and 2) were simultane-
ously solved by the computational fluid dynamics pack-
age of Fluent (Fluent Inc., Lebanon, NH, USA). The
implicit solver formulation was used for solving the par-
tial differential equations in a segregated manner. A spa-
tially second-order upwind discretization scheme was
used to minimize numerical dissipation.
2.2.4. Assumpti ons
The numerical model was based on the following as-
sumptions: (A) steady flow rate [15,16]; (B) rigid vein.
Veins, which are normally considered collapsible tubes,
can be assumed to be rigid when fully inflated. Such is
the case with the cephalic vein while the arm is below
the level of the heart [17]; (C) the flow is laminar and the
fluid is Newtonian and incompressible; (D) the catheter
is sealed at its non-invasive end, and is placed inside the
vein without injection or withdrawal of fluids through it.
This was done because for most of the time the SPC is
in-situ, it is actually not in use and SPCT still develops.
2.2.5. G eometry and Computational Meshing
The computational model geometry was that of a 3D
cannulated cephalic vein (Figure 2). The 3D geometry
and the meshing were designed using GAMBIT (Fluent
Inc.). While the cephalic vein diameter usually ranges
from 1.9 - 3.9 mm, reaching from 1mm to over 6 mm in
actual measurements [14,18,19], we chose a 5 mm inner
diameter and 85 mm long straight tube section to make it
compatible with the in vitro model in our laboratory. A
16 gauge (1.3 mm inner diameter, 1.7 mm outer diameter)
catheter was placed inside the vein with an entrance ori-
entation of 30˚ relative to the vein symmetry axis. The
catheter length from its contact with the vein was defined
as 25 mm, and was set to be sunk 0.25 mm into the vein
wall and underlying tissue to simplify the meshing in the
contact area. The vein length upstream to the catheter
insertion site was extended by 23 mm to allow the flow
to develop before it reached the catheter. The catheter lumen
length was set for 10 mm from the catheter tip back-
wards. The model was cut along its plane of symmetry
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O. M. Rotman et al. / J. Biomedical Science and Engineering 6 (2013) 6-13 9
Figure 2. The computational model geometry: (A) side view of
the entire geometry, (B) side view zooming in on the catheter
inside the vein, (C) further zooming in on the catheter lumen
and tip, and (D) diagonal view of the model. Legend: (1)
catheter entrance, (2) catheter lumen, (3) catheter tip, (4) vein
lumen, (5) vein entrance, and (6) catheter insertion site.
(plane YZ) to save computational time.
The 3D geometry was converted with GAMBIT (Flu-
ent Inc.) into discrete mesh using 1,010,690 hexahedral
and tetrahedral elements. Maximum element size was
8.75 × 103 mm3, and the total volume of the computa-
tional model was 805.29 mm3.
Mesh convergence study was performed to ensure that
the solution in each case differed by no more than 1% in
the velocity values.
3.1. vWF C on ce n tr at i on s
The data are summarized in Figure 3. In experiment
repetition number 2, the concentrations of samples Con-
trol 1 - 3 and Test 2 - 3 at t = 0 were manually set to 0
mU/ml, since the values achieved by the calibration
curve were negative and close to zero. The data of Con-
trol 3 and Test 3 for t = 40 minutes in experiment repeti-
tion 2 were discarded from the statistical analysis due to
inappropriate manipulation of the relevant samples. The
elevation in vWF concentration in the medium over time
was considerably higher for most samples of the test
group compared with the corresponding samples of the
control group. The overall time course was significant (p
< 0.001) in both the control and test groups. The interac-
tion between time course and experimental repetition
was not significant (p = 0.986). Most importantly, the
interaction between time course and groups was signifi-
cant (p = 0.013), evidenced by the increased release of
vWF in the test group. The averages of the time steps
also differed significantly between the control and test
groups (p = 0.03).
3.2. Cell Morphology
Cells in the control group (Figure 4) showed no differ-
ences between t = 0 and t = 60 in cell alignment and con-
fluence density: at both time points cell confluence re-
mained almost 100% with no signs of cell mitosis or
stress, and the cells remained stretched with no preferred
orientation in the field of view. In contrast, the test group
cells exhibited significant changes between t = 0 and t =
60: their number had decreased, resulting in cell-free
areas throughout the field of view; some of the remaining
ones had assumed a round shape, suggesting they were
about to detach, and several had become less smooth,
denoting stress. In addition, the medium contained a sub-
stantial amount of debris (not seen in the images).
Figure 3. Graphic representation of vWF concentrations in the
medium, measured by ELISA. The concentrations are pre-
sented as mean ± standard deviation.
Figure 4. Images of HUVEC taken at time points t = 0 minutes
((A) and (C)) and t = 60 minutes ((B) and (D)). The white
dashed lines mark areas clear of cells. The white arrows point
to round shaped cells.
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O. M. Rotman et al. / J. Biomedical Science and Engineering 6 (2013) 6-13
3.3. CFD Simulation
The fluid path-lines smoothly followed the catheter outer
surface at the insertion site, in the region where the
catheter met the opposite wall of the vein, and along the
catheter body. The catheter insertion site was free of flow
disturbances and there was no apparent effect on the flow
patterns downstream along the catheter wall. Two unto-
ward phenomena were noticed: 1) As the flow passed the
catheter tip (Figure 5), a small recirculation region ap-
peared partially inside the catheter lumen. The recircula-
tion region was 1.7 mm long in the 60 ml/min flow rate
case, with no significant difference at the other examined
rates (range 1.64 mm to 1.82 mm). The surface area in
which there were WSS below 0.1 Pa grew larger as the
flow decreased. Goel and Diamond [18] showed that the
maximum WSS at which red blood cells adhere to plate-
lets, neutrophils, and polymerized fibrin—adhesion that
supports increased thrombus formation—is 0.1 Pa. The
WSSs in the vein model without the catheter were 0.135
Pa, 0.23 Pa, 0.30 Pa, and 0.38 Pa for flow rates of 28
ml/min, 45 ml/min, 60 ml/min, and 75 ml/min, respec-
tively. (2) The second phenomenon was a significant
decrease in the flow velocity and WSS (Figure 6) on
both sides of the catheter (along the x axis) as a result of
an enlarged boundary layer. The mean axial velocities of
the profiles with the catheter (Figure 7) were reduced on
average by a factor of 2.76 due to the catheter. In con-
trast, maximal axial velocities (along the y axis) in-
creased in the center of the vein lumen due to the cathe-
ter: increases of 0.81 cm/s, 1.18 cm/s, 1.39 cm/s, and
1.53 cm/s for the flow rates of 28 ml/min to 75 ml/min.
This, however, did not significantly affect the vein
maximal WSS on the y-axis (0.2 Pa, 0.31 Pa, 0.41 Pa,
and 0.51 Pa for flow rates of 28 ml/min, 45 ml/min, 60
ml/min, and 75 ml/min, respectively).
The elevated concentrations of vWF in the test group
indicate that the HUVEC was stimulated by the catheter
weights. The slight rise in vWF over time in the control
group can be accounted for by the known normal secre-
tion of small amounts of vWF by endothelial cells [19].
This is supported by the absence of change in cell shape
and confluence in this group (Figure 4). The large dif-
ference in vWF concentration between experiment repe-
titions 1 and 2 can be attributed to the fact that each of
the repetitions was performed independently on cells
from a different passage [20]. Despite the wide variation,
the vWF release profile of the test group differed sig-
nificantly over time from that of the control group in
both independent repetitions. The higher release profiles
reflected in the mean concentrations suggest ongoing
stimulus of the test group cells.
Figure 5. Side view of the catheter tip region with vectors de-
scribing the path-lines of flow, indicating a recirculation region
at the catheter tip.
Figure 6. Top view of the vein WSSs in regions surrounding
the contact area between the catheter and the vein. The WSSs
are presented with an upper limit of 0.1 Pa.
Unlike sustained hydrostatic pressure, the catheter is a
physical impediment to metabolite transport processes
between the culture layer and the nutrient medium.
While sustained hydrostatic pressure of upto 7 mmHg
stimulates HUVEC proliferation [21], a relatively low
physical pressure of less than 1 mmHg in our study
caused cell activation and death. The bald areas clearly
seen in Figure 4(D) are those of the greatest physical
load and most probably the contact areas between the
cells and the catheter pieces. Moreover, in areas where
the cells remained dense, some of them changed shape
from elongated and stretched to round, indicating a dis-
turbance or stress.
The mean axial velocities in proximity to the vein wall
(on the x-axis), obtained by CFD analysis, were reduced
on average by a factor of 2.76 when the catheter was
placed. The WSSs in this region were also reduced, cre-
ating a surface area surrounding the catheter of WSSs
below 0.1 Pa (Figure 6). This reduction was caused by
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O. M. Rotman et al. / J. Biomedical Science and Engineering 6 (2013) 6-13
Copyright © 2013 SciRes.
Figure 7. (A) Front view of the axial velocity contours at 60 ml/min vein flow: Topvein with a catheter.
Bottomvein without a catheter. The horizontal white lines with rectangles (vein with a catheter) and tri-
angles (vein without a catheter) are the lines along which velocity profiles were sampled for comparison.
(B) Axial velocity profiles for the different vein flow rates examined, with and without a catheter, focusing
on the region between the catheter and the vein wall on the x-axis (marked in A by a red rectangle).
an enlarged boundary layer between the vein wall and
the catheter body. It was expected that the lower WSSs
themselves would not activate the endothelial cells, as
the WSSs in veins were naturally very low. Nor did the
presence of the catheter have a marked effect on the
WSSs. We believe that the major effect of the reduced
velocities and WSS was to create a supportive environ-
ment for adhesion of rolling leukocytes and platelets to
activated endothelium, and to each other, promoting a
local inflammatory process in the vein wall and throm-
bosis formation in the lumen [12]. This mechanism is
supported by Goel and Diamond’s work [18] showing
that a WSS below 0.1 Pa enables the circulating red blood
cells to adhere to platelets, neutrophils, and polymerized
fibrin, resulting in thrombus growth. The in vitro results
confirmed our hypothesis that the endothelial cells would
be activated in the precise location of contact between
the catheter and the vein wall, the same location where
we observed that significantly reduced flow velocities
and reduced WSSs. While our hypothesis appears to
have been proven, it needs confirmation from studies of
endothelial activation under direct flow conditions.
Another important flow disturbance was the recircula-
tion region that appeared at the catheter tip, partially in-
side the catheter lumen. A recirculation region in such a
location can amplify local inflammatory and coagulatory
processes, and slowly dilute the catheter lumen with
blood products that may clot and eventually block the
lumen and render it non-functional.
According to the CFD results, the flow rate did not
seem to have a significant effect on the flow field, as the
flow patterns for all simulated rates smoothly followed
the catheter outer surface from insertion site to catheter
tip. Nor did the size of the recirculation region at the
catheter tip appear to be affected by the flow rate. The
reduced flow rate did, however, slightly increase the re-
gion of very low WSSs around the catheter. It might be
that low flow rates create a larger surface area with the
potential to promote the rapid thrombus formation.
The findings of this research support the hypothesis
that biomechanical factors participate in SPCT patho-
genesis, and explain the mechanisms of the common
complication associated with peripheral catheters. Most
of the improvements in SPCs in recent years consisted of
changes in the polymeric material of the cannula. Our
results point to the need for geometric modifications to
the SPC that will eliminate the contact between the
catheter body and the vein wall and avoid the formation
of flow stagnation and recirculation regions. Two such
geometric modifications are illustrated in Figure 8: sig-
nificant shortening of the SPC to avoid contact between
the cannula and the opposite vein wall, and a protrusion
on the cannula outer surface as an anchor to prevent the
cannula from slipping outside the vein.
The biomechanical mechanism suggested by the re-
sults of the numerical simulations and in-vitro experi-
ments conducted in this study involves prolonged irrita-
tion and activation of the endothelial cells by the SPC
due to physical contact between them, and flow distur-
bances caused by the catheter that promoted local in-
flammatory and coagulatory processes. These flow pat-
terns most likely support, rather than initiate, local reac-
As a pioneering work, this study has limitations that
O. M. Rotman et al. / J. Biomedical Science and Engineering 6 (2013) 6-13
Figure 8. Example of an SPC with geometric modifications. (A)
Comparison of the suggested SPC and a commercial SPC. (B)
Illustration of the suggested SPC positioned in a vein. The ar-
row points to the protrusion on the catheter outer surface.
will need to be addressed in future research. The most
serious one is that the in vitro experiments and the nu-
merical simulations were conducted separately. Because
incorporating a flow system into the HUVEC experi-
mental setup would have diluted the vWF concentrations
to an undetectable level, we chose at this stage to inves-
tigate the flow and the catheter-HUVEC interaction sepa-
rately. We are planning a second generation system that
will link the simulations to the experiments in a more
robust manner. Another limitation is the difference be-
tween the time scale simulated in vitro with the HU-
VEC and the time scale for SPCT in vivo. The 60-min-
ute period chosen for the in vitro experiment was found
to be sufficient after several trials with different scales.
While in clinical practice the time scale for SPCT is ap-
proximately 3 days [22], our choice of 60 minutes is jus-
tified on a number of fronts. As mentioned above, bald
areas free of cells remained in the culture at 60 minutes,
after which the cell numbers were no longer comparable
and there was no reason to continue the experiment. The
time scale is affected by factors other than the tested bio-
mechanical ones: for example, the in vitro test had no
flow, which meant that active substances secreted by the
cells over time did not flush away. The absence of this
process amplified the endothelial activation and made the
time scale shorter. Previous works that investigated vWF
secretion by chemical stimuli on cultured endothelial
cells also used a 60-minute time scale [19,23]. Michaux
et al. [19] reported that after 1 hour of chemical stimuli
(by Calcium ionophore A23187 and by phorbol ester
PMA), the HUVEC had secreted about 40% of their total
vWF. Another limitation of the study was that irritation of
the vein wall by the catheter tip and possible mechanical
injury during the catheter insertion were not investigated.
Such injuries to the vein wall could expedite local in-
flammatory and coagulatory reactions. We chose to focus
on more “chronic” biomechanical factors that take place
while the SPC is in-situ, and not on factors that can be
avoided by better manipulation by the medical staff.
Despite of the limitations, this is the first study to in-
vestigate biomechanical aspects of SPCT. The results
support our hypothesis and lay the groundwork for more
comprehensive investigations that will examine the effect
of different pressure loads on HUVEC activation, the
incorporation of flow in the in vitro experiments, and the
simulation of the bending of the SPC on the vein wall.
Such studies will enhance our understanding of the ef-
fects of load on endothelial cells.
The study was partially supported by the Drown Foundation and the
Berman Fund.
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