Briana Conners, Junior, Chemical Engineering and
Ken Okoye, Junior, Biomedical Engineering
Initial project plan report: Project #2 Hemodynamic Evaluation of Arteriovenous Fistula
Abstract
Arteriovenous fistulae are the preferred method of access for hemodialysis due primarily to its
relatively low occurrence of infection and thrombosis. The fistula is created by a vascular surgeon
between the radial artery and the parallel cephalic vein to circumvent the high-resistance capillaries in
the extremities distal to the fistula and increase the volume of blood flow in the target blood vessels. An
arteriovenous fistula is created by joining the end of the artery to the vein. The resulting lower
resistance route significantly increases the amount of blood flow which facilitates hemodialysis in
terminal renal patients. The changes in blood flow pattern trigger a remodeling of the blood vessels.
Ideally the blood vessels dilate to accommodate the increased flow. However, 23-46% of all fistula fail
when stenosis, narrowing of the blood vessel, occurs as a result of neointimal hyperplasia (NIH). This
problem is being investigated by various studies. While the exact pathway of the neointimal hyperplasia
is unknown, there is a correlation between wall shear stress, frictional forces exerted by blood on the
inner surface of the vessel, and the occurrence of NIH. Given this relationship, this project aims to gain
an understanding of the relationship between the angle at which the vessels are joined through
anastomosis and wall shear stresses exerted by the increased blood flow following the arteriovenous
fistula.
Background
Patients with end-stage renal disease (ESRD) must attend dialysis a few times each week to have their
blood filtered. In order to do so, the vascular system must be accessed and a low resistance, high flow
path created. Through the connection of a vein and artery, arteriolar beds can be avoided and the blood
flow rate increases to minimize dialysis time. Thus, a good vascular access should provide adequate
blood flow for dialysis. It should also have a superficial position for the ease of access, a long life span,
and minimal complication rate. 28 However, due to failures of the current methods for vascular access,
there is a huge clinical problem causing clinical morbidity and economic strain for the ESRD patients 29.
PTFE Graft (polytetrafluoroethylene)
One vascular access method that has been extremely common in the US in the past is the PTFE grafts2.
This VA involves the PTFE graft used as a bridge between an artery and vein. It can be used for either
superficial or deep veins and is punctured during hemodialysis. The wide-spread use of PTFE grafts
occurred because of the ease of the surgical technique, the immediate availability of the graft for
puncture, and the need of high blood flow for high-efficiency, short-duration hemodialysis sessions.
There are also financial disincentives against the arteriovenous fistula alternative. However, it has been
increasingly recognized that outcomes of PTFE grafts are inferior5.
Arteriovenous Fistula
Thus, the arteriovenous fistula (AVF) is becoming a popular method of vascular access. AVF’s involve the
surgical connection of the end of a vein to the side of an artery. The AVF is the preferred form of VA
because it has the longest survival rate and fewest complications2. These avoided complications include
lack of infection and lack of thrombosis (clotting) 1. Through these advantages, patient survival
increases and costs are reduced, and so AVF’s are the focus of current researchG2.
Mature AVF Characteristics
In order to be successful and considered “mature”, a fistula must reach flow rate, diameter, and time
constraints. There are no well-established criteria, but generally a blood flow of 500 ml/min and a
diameter of at least 4 mm are needed for an AVF to adequately support the dialysis (3-5hr) therapy3.
These parameters should be met within 4 to 6 week or the fistula will be deemed an early failure3. In a
functional fistula, typical blood flow rates will be 500-2000 ml/min for a forearm fistula and 500-3000
ml/min for an upper arm fistula. For reference, mean blood flow in the brachial artery at rest is around
50 ml/min, and it is 25ml/min for the radial artery 2.
Vein Remodeling
The blood vessels achieve these much higher flow rates through remodeling. The high volume flow
exerts a pressure perpendicularly to the wall, so all layers sense the force and are strained28. The apical
cell surface is also strained by the increase in wall shear stress, the frictional force generated by the
blood flow which increases from 5 dyne/cm2 from to 24.5 dyne/cm2 after fistula creation3. The arterial
endothelial cells sense the sudden increase in flow and try to maintain the baseline physiological level
by dilating. The mechanism responsible is the increase in the bioavailability of nitric oxide which is the
strongest endogenous arterio-dilating agent by the endothelium cells28. The NO causes smooth muscle
relaxation2. This response usually occurred rapidly, but when extremely high shear stress was induced,
it required up to 6 months12.
This response is limited though and further fragmentation of the elastic lamina is required for chronic
high WSS levels2. A more prolonged increase in flow causes morphological changes in the arterial wall.
This includes the degradation and fragmentation of the basal membrane, or internal elastic lamina18, by
matrix metalloproteinases which are activated by NO. Through this process, the diameter of the vein
increases, while the intima media thickness remained unchanged5. However, one year later the radial
artery wall does appear to thicken most likely due to the circumferential wall stress from dialtion2.
AVF Failures
Unfortunately, a significant number of fistulae (28 to 53%) fail to mature adequately to support dialysis
therapy. Frequently, these patients with failed fistula are consigned to a tunneled dialysis catheter for
dialysis therapy and receive inadequate treatment and increase their risk for infection3. As an indicator,
if the vein and artery dilate and achieve a rapid increase in blood flow immediately after surgery is a
determinant of if the fistula will mature. Other factors include surgical experience, gender and evidence
of extensive vascular disease. Interestingly, some studies show vessel size does not seem to have an
impact on fistula success rate beyond the limit preoperative size2.
Complication Causes
Some failures occur when arteries or veins do not dilate, possibly due to the severe vascular disease of
the patient. Currently, the single most important reason for an AVF to fail to mature is juxtaanastomotic stenosis from accelerated venous neointimal hyperplasia (NIH), thickening of the vessel
wall3. Venous stenosis has been found in 65-100% of angiographically evaluated failing fistulas and
more than half are located either in the vein immediately downstream of the anastomosis or involve the
anastomosis itself. 2.
NIH has also been correlated to regions of low or oscillating wall shear stress in which endothelial cells
cannot align in the direction of the flow. These low WSS areas are particularly likely to occur at the
arteriovenous anastomosis because of differences in compliance between the artery and the vein.
Excessively high WSS can also damage endothelial cells and activate platelets that lead to NIH3.
Similarly, NIH may also be caused by the injury response to the surgical trauma in the endothelium
during the fistula creation2. Endothelium cells look abnormal when analyzed, and there are areas of
exposed underlying basement membrane and intima. The smooth muscle cells in the neointima are
disoriented. Vascular wall calcification and collagen deposits are another common occurrence that
contributes to the arterial stiffness. The endothelial dysfunction impairs the release of nitric oxide and
arterial dilation for adequate blood flow2.
Methods
In previous studies, Dr. Rupak Banerjee and his group exploited the properties of perivascular probes,
Doppler flow wires, intravascular ultrasound, and CT angiography to measure and model the observed
fluid dynamics, namely blood flow and pressure, inside of porcine in vivo models. By taking images in
slices, and reconstructing them to create 3D models of these fistulae using software ackages like Fluent,
and using what is called the Finite Volume Method, we can recreate not only a the vessels, but the
types of forces exhibited by the blood inside of these vessels. These are the same techniques that the
REU students assigned to this project plan to use to measure these parameters in different
configurations of arteriovenous fistula from which they will calculate wall shear stresses.
Results
To follow
Conclusions
To follow