Abstract
Systems for embolic protection are applied during the dilatation and the implantation of stents in the carotid artery. They are used to avoid downstream drift of arterial plaque particles which may be released during the intervention. Such particulate debris increases the risk of stroke when reaching and occluding even minor cranial vessels. Embolic protection devices (EPD) are intended to collect such particles during intervention and to finally remove them.
A test setup was developed in order to assess the effi-cacy of commercially available EPDs. The setup considers the introduction of relevant particles, as well as typical anatomic conditions. The EPDs could be tested using curved and ovalized vessel types to simulate stressed vessel conditions. Furthermore, a method for counting the particles was established to quantify collected particles in the EPD, the leaked particles and those which were left behind in the vessel.
1 Introduction
In western industrial countries stroke is the third frequent reason for death and the most frequent cause for disabilities. In Germany, 200.000 to 250.000 patients per year suffer from stroke, and in total about 700.000 persons per year are affected by consequences of stroke [1].
Ischemic strokes are caused for the most part by stenosis or occlusions of the A. Carotis [2]. Embolic complications may occur also during carotid artery interventions, such as angioplasty or stent implantation. Invasive manipulations bear the risk of releasing particulate debris which is carried by the bloodstream and leading to neurovascular occlusion and finally to neurological impairment. Cerebral protection systems have been developed which either act as filters (EPD) or flow reversal devices [3]. Different designs and working principles are available. The presented setup is intended to assess the efficacy of such devices in vitro under simulated vessel conditions.
2 Methods
Basic anatomical conditions, such as vessel diameter and volume flow, were realized. Estimated values are given in Table1 [4].
From these data, the maximum volume flow in the A. carotis interna was calculated to 945 ml/min at a vessel diameter of 5 mm.
While the anatomy of the carotid bifurcation implies the use of a y-shaped bifurcation model (Figure 1) this approach is associated with a couple of limitations for particle quantification if only one branch is treated by the EPD.
First approach of the test setup with bifurcation with 1. peristaltic pump 2. tubing 3. pre-filter 4. hemostatic valve 5. bifurcation 6. polycarbonate filter 7. tubing.
A relevant configuration is realized by reducing the setup to only one branch with flow and diameter of the target vessel (A. carotis interna). This setup without any bifurcation is shown in Figure 2.
Anatomical conditions of the different vessels [4].
| vessel | diameter [mm] | systolic flow rate [m/s] | end-diastolic flow rate [m/s] |
|---|---|---|---|
| A. carotis communis | 7 + 1 | 0.7 + 0.04 | 0.19 + 0.02 |
| A. carotis interna | 5 + 1 | 0.8 + 0.05 | 0.3 + 0.10 |
| A. carotis externa | 4 + 1 | 0.8 + 0.05 | 0.2 + 0.05 |
Test setup without a bifurcation, 1. peristaltic pump 2. special tubing 3. flow sensor 4. pre-filter 5. pressure sensor 6. hemostatic valve 7. tubing 8. test track 9. polycarbonate filter.
The peristaltic pump (Watson Marlow, 323 S/D) is able to produce the required flow rate of 945 ml/min. The flow is measured by an ultrasonic flow sensor (Levitronix, LFS-008). The 2-stage pre-filter (Sartorius Stedim Biotech, Sartobran 150: pore sizes 0.45 µm and 0.2 µm) ensures a particle free test solution. The pressure sensor determines the flow resistance of the inserted EPD which may change with the number of collected particles. The EPD to test is inserted through a hemostatic valve. The particles which pass the EPD are collected in a polycarbonate filter with a track-etch membrane. The filter membrane can be removed and analyzed under microscope view. A second and more effective method uses a glass filter (pore size 40 µm) to collect the passing particles. The procedure to test the EPD is described below. The setup is shown in Figure 3.
The test setup is rinsed for 10 minutes with particle free pure water without any EPD and particles to achieve a particle free setup and test solution. Potentially released particulate matter is simulated by artificial particles which are added to the clean solution. Thus, their absolute number is known and the portion of collected, removed and remaining particles can be assessed.
The particles (150 µm, Micromod GmbH) used for this purpose are made from polystyrene and added by a COOH coating. The coating prevents the particles from agglomeration. The size is chosen to be larger than the nominal pore size of the EPD filters. This means that the EPD should be able to withhold all particles by filtering. The particles are added to a PBS buffer solution in a glass bottle. For each test 2000 - 4000 particles are used. The number of particles depends on the size of the used particles. The larger the particles, the lower is the number of particles. Afterwards, the bottle containing PBS buffer and particles is connected to the test setup. For a homogeneous distribution the solution is constantly agitated by a magnetic stirrer. Then, the EPD is inserted through the hemostatic valve and advanced until the target vessel section. The insertion is performed according to the individual instruction for use of each EPD to be tested. Two different vessel models are used. The EPD to test can be placed in a curved (Figure 4) and in an oval vessel model (Figure 5). The latter is deformed to only 70% of its original diameter in order to simulate particularly stressed vessel conditions.
Schematic of the test setup for the forward flow direction.
Curved vessel model.
The test is started by rinsing the system with a volume flow of 945 ml/min for 5 minutes. The particles are carried out of the glass bottle through the circuit and including the EPD. After 5 minutes the test is stopped and the glass filter is removed. The collected particles in the glass filter were leaked by the EPD. They were analyzed after flushing the glass filter with ethanol in the clean room. The solution is kept, and the particles are counted offline by a particle counter (HIAC ROYCO 9703) according to USP 788.
Oval vessel model.
Schematic of the test setup for the backward flow direction.
Then the EPD is withdrawn into the hemostatic valve and thus removed from the flow circuit. A clean glass filter is mounted to the test setup which is changed to the configuration as shown in Figure 6. The intention is to collect the particles which were neither caught by the EPD nor the downstream glass filter by back-flushing. The test is started again for 5 minutes. At the end of the test the second glass filter is removed, too. The particles are washed out and counted as described before. The result gives information about the lost particles while withdrawing the tested EPD.
3 Results
The results of EPD measurements are compared to a test using the same procedure but without an EPD (particle recovery) for both vessel configurations. The results are shown in Figure 7.
The value of the particle counts of the test without an EPD is the average of three single measurements and shows that no particles remain in the tubing. The recovery of more than 100 % seen in Figure 7 of inserted particles is caused by statistical variations during the particle counting process. As expected, there are no particles found with the inversed flow direction (respective after retraction) because all particles washed out of the tubing after the first test. In this case it could be shown that the setup is suitable for testing the EPDs without missing particles in the system.
Percentage of particle recovery from curved and oval vessel configurations.
As an example, the results of the measurement with the EPD Angiogard RX (Cordis) EPD are shown in Figure 8. The particle counts are presented for the curved and oval vessel model, respectively.
In the curved vessel model the EPD Angiogard RX collected 29.1 % of the inserted particles. 70.1 % passed the EPD and were found on the glass filter. After retraction of the EPD 7.1 % of the particles are found on the second glass filter. This result demonstrates that 7.1 % of the particles caught in the EPD are lost during retraction. In the oval vessel model the EPD prevented 10.9 % of the inserted particles from flowing downstream. This means, that 89.1 % passed the EPD. After retraction of the EPD 12.5 % of the collected particles are found in the glass filter.
Particle counts of the EPD Angiogard RX in the curved and oval vessel model.
4 Conclusion
The developed test setup is suitable for testing EPD systems. The measurements without an EPD showed that no particles are supposed to remain in the tubing. Statistical variations were in the typical order of measurements for particulate matter. In conclusion , the setup may provide relevant results with respect to efficacy of EPD at defined vessel conditions.
The tested EPD showed a number of leaked particles in both vessel models. During retraction of the EPD further particles were lost. However, assessment of device efficacy should also consider that the design of the vessel models may influence the results. Curved and oval vessels should simulate critical conditions for EPD. Vessel surface and compliance (weakness) could be a limitation of the setup. So the high counts of particles may be attributed to the smooth surface of the vessel models. On the other hand, the high particle recovery rate enables quantitative reproducible measurements.
Further studies will show how effective different types of EPD are, while used in this technically well described setup.
Author’s Statement
Conflict of interest: Authors state no conflict of interest. Material and Methods: Informed consent: Informed consent has been obtained from all individuals included in this study. Ethical approval: The research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance the tenets of the Helsinki Declaration, and has been approved by the authors’ institutional review board or equivalent committee.
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© 2015 by Walter de Gruyter GmbH, Berlin/Boston
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