Dissemination level: Public
Heart-e-Gel project:
“Microsystem integration based on electroactive polymer
gels for cardiovascular applications”
Deliverable 6.1:
“Adapted pulse duplicator working with hemodynamic
profile at intended vascular locations”
Responsible Beneficiary:
__________________________________________________________________________
FP7-ICT-2009-5 - Small or Medium-scale Focused Research Project
STREP: CP-FP-INFSO Heart-e-Gel 258909
ICT-5-3.9 – Microsystems and Smart Miniaturised Systems
1
KU Leuven
Due Date:
1st March 2011
Submission Date:
15th April 2011
1
TABLE OF CONTENTS
1
Table of Contents............................................................................................. Error! Bookmark not defined.
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Introduction .................................................................................................................................................... 4
4
Artificial Circulation System ............................................................................................................................ 4
5
Results ............................................................................................................................................................ 6
6
Conclusion ...................................................................................................................................................... 7
7
Figures ............................................................................................................................................................ 8
8
References .................................................................................................................................................... 17
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FP7-ICT-2009-5 - Small or Medium-scale Focused Research Project
STREP: CP-FP-INFSO Heart-e-Gel 258909
ICT-5-3.9 – Microsystems and Smart Miniaturised Systems
2
__________________________________________________________________________
FP7-ICT-2009-5 - Small or Medium-scale Focused Research Project
STREP: CP-FP-INFSO Heart-e-Gel 258909
ICT-5-3.9 – Microsystems and Smart Miniaturised Systems
3
2
INTRODUCTION
Several different types of artificial circulation systems have been described in literature, their morphology
depends strongly on the study protocol
1 2 3 4 5 6 7
. In vitro circulations have several advantages: a lot of
parameters are controllable (pulse rate, pressure, resistance, compliance), the setup is reproducible, large
numbers of data can be easily obtained. On the contrary in vitro models are often a balance between
reduction in mechanical complexity and accuracy of the investigation. Ideally artificial circulation systems
should be capable of producing pulsatile and nonpulsatile flow conditions as these are encountered under
physical conditions. For example, in the aorta the flow rate is close to 5000ml/min with a systolic pressure of
120 mm Hg and diastolic pressure of 80 mm Hg, with a duration of the systolic phase of one third of the
cardiac cycle and with a frequency of the pulsatility of 60 beats per minute (bpm). On the other hand, in veins
there is a continous, low-pressure, nonpulsatile flow. Most of the described systems cannot be easily adapted
to produce these variable flow conditions. It should also be possible to do experiments with whole blood as a
working fluid, so biocompatible surfaces and low mechanical forces are needed to achieve a low hemolysis
index
8 9
. The aim of this deliverable is to produce a mock circulation system that mimics the pressure and
flow patterns of the human arterial, venous and ventricular sytem. This system is used to evaluate the
hydrogels as they may have a wide range of applications and should be tested under a wide range of flow and
pressure conditions.
3
ARTIFICIAL CIRCULATION SYSTEM
An in vitro circulation system was build that consists of four elements (figure 1): the pump system, the
circulatory system, the test compartment module, and the acquisition and analysis monitoring system.
The pump system consists of two elements placed in parallel: a roller pump and a pneumatically driven
ventricule. The roller pump (Sarns Inc, Ann Arbor, Michigan, USA) generates
a constant flow which can be changed according to the application by
__________________________________________________________________________
FP7-ICT-2009-5 - Small or Medium-scale Focused Research Project
STREP: CP-FP-INFSO Heart-e-Gel 258909
ICT-5-3.9 – Microsystems and Smart Miniaturised Systems
4
adjusting the rotations per minute (rpm). The second element is a pneumatically driven ventricle of 60 ml
(Ventricle Assist Device, Medos, Stolberg, Deutschland). This is used to induce pulsatility within the generated
flow. The rate, inflation pressure, suction pressure and relative time of systole are adjustable, allowing
measurements under a wide range of hemodynamic consitions.
The pulsatile pump system is connected with a reservoir, which is mounted 5 cm above the horizontal plane of
the test compartment. In front of the venous reservoir is a heat exchanger (D720A Helios, Sorin Group,
Mirandola, Italy) to keep the temperature at a physiologic level (36-38°C). The system can be filled with
several solutions: water, a blood analog (a 40% glycerol/water mixture to simulate the viscosity of blood or
Krebs Henseleit solution to simulate the composition of blood) or anticoagulated blood. During the
experiments the system is filled with 2000 cc of liquid. For maintance of the water quality 2 ml Prothermal
(Lucernachem, Luzern, Switzerland) per 1 liter test fluid can be added. After the experiment the fluid is filtered
to obtain information about the embolic characteristics with a 0.2 micron filter Pall laboratories (Port
Washington, NY, USA).
The circulatory system consists of a closed, Windkessel, cylindrical chamber (Plexiglass, height 13 cm,
diameter 12 cm), which represents the vessel wall distensibility and a tourniquet that squeezes a tube
segment in order to simulate circulatory system peripheral resistence. The compliance chamber is placed
between the pump system and the test compartment. A manual inflation system is placed on top of the
chamber to modify the volume of compressed air inside the chamber, and so modify the compliance within
the artificial circulation. The compliance (C=V/P) of the chamber was calculated measuring the volume (V)
of water needed to obtain a pressure increase (P) of 40 mmHg. The compliance was measured in the
physiologic pressure range (0 mm Hg – 200 mm Hg) for different amounts of air in the chamber (figure 2). By
squeezing a tube segment with a tourniquet, which is placed between the test compartment and the venous
reservoir, the internal area is reduced and the circulatory system peripheral resistance is augmented. Both the
compliance chamber and circulatory resistance system are used to obtain physiologic wave forms of flow and
pressure.
__________________________________________________________________________
FP7-ICT-2009-5 - Small or Medium-scale Focused Research Project
STREP: CP-FP-INFSO Heart-e-Gel 258909
ICT-5-3.9 – Microsystems and Smart Miniaturised Systems
5
The test compartment module (figure 3) is made of plastic and it is possible to fit different vessel models in.
These vessel models are self-made latex vessels or animal vessels obtained from the abbatoir. The different
latex vessels models (figure 4) for the test compartment are obtained by repetitively dipping a mould in a
silicone rubber latex solution. Each coat is allowed to dry for approximately 30 minutes. When eight layers
were obtained the model was immersed in warm water for 1 hour. This soaking pocess aided the model to be
removed from the mould. Depending on the study protocol several adjusments and side-branches can be
made. The connections between the circulatory system and the different components are made of
cardiopulmonary bypass tubing (3/8 and 1/2 inch).
The acquisition and analysis monitoring system is composed of a set of transducers. An ultrasonic flow
transducer (HT110, Transonic Systems, Ithaca, NY, USA) is placed downstream of the pumps and is used to
acquire hydrodynamic information of the mock system. The flow probe is callibrated for the tubing size, the
test fluid and the temperature. Pressure transducers (Edwards Lifesciences LLC, Irvine, CA, USA) are placed
before and after the test compartment module to investigate the behavior of the simulator. The pressure
monitor (HP 78534A Monitor, Hewlett Packard, Loveland, Colorado, USA) is calibrated before each serie of
measurements. A temperature transducer is placed in the venous reservoir to keep temperature within
physiologic level. To evaluate the influence of hydrogels on the elasticity of the vessel wall, the displacement
of the vessel wall can be monitored with a sonomicrometry system (Sonosoft, Sonometrics cooperation,
London, Canada). All measured signals were acquired by a data acquisition board (USB-6008, National
Instruments, Austin, Texas, USA). The signals are sampled at 1 kHz and low-pass filtered at 10 Hz in orde to
acquire a reasonable sampling rate and to remove unwanted signal components. A monitoring program is
written in LabView SignalExpress (National Instruments, Austin, Texas, USA).
4
RESULTS
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FP7-ICT-2009-5 - Small or Medium-scale Focused Research Project
STREP: CP-FP-INFSO Heart-e-Gel 258909
ICT-5-3.9 – Microsystems and Smart Miniaturised Systems
6
For testing the electroactive hydrogel in different applications, the hemodynamic setting can be modulated to
obtain venous or arterial hemodynamic conditions. To obtain venous conditions the pneumatically driven
ventricle is switched of, there is a high compliance within the compliance chamber and the resistance is set on
a low level. In this way a constant, low pressure flow is generated. To test the occlusion capacity of the electroactive hydrogels within a venous environment, vessel models can be mounted within the test compartment
module as given in figure 5.
To obtain arterial conditions the settings of the pneumatic ventricle are defined as follows: systolic inflation
pressure is 300mm Hg, the diastolic suction pressure -20mm Hg, the heart rate 60 beats per minute, and the
duration of the systole is 35% of the cardiac cycle. As given in figure 6, it is possible to obtain arterial pressure
and flow curves which resemble the normal arterial curve very well. There is a frequency of 60 bpm, a systolic
lenght of approximately one thirth of the cardiac cycle, during diastole there is a rapid decrease in pressure
with a slower decline thereafter and the pulse pressure is around 40 mm Hg. The systolic and diastolic
pressure can be changed by adjusting the resistance and the compliance. The overal flow can be diminished by
reducing the rotation per minute of the roller pump. These settings can be used to test the occlusion of an
artery or abnormal arterio-venous connection (figure 7) and the occlusion of an aneurysm sac (figure 8).
5
CONCLUSION
This artificial circulation will enable future research of hydrogels. In comparison with other pulse duplicators
this system can generate pulsatile and nonpulsatile flow and allows testing of these devices in a broad range of
hemodynamic features. As the circulation can be filled with blood or an analog the influences of the blood
components on the device can be evaluated as well as the influences of the device on blood. In this way
protein, lipid and cellular infiltration within the device can be evaluated.
__________________________________________________________________________
FP7-ICT-2009-5 - Small or Medium-scale Focused Research Project
STREP: CP-FP-INFSO Heart-e-Gel 258909
ICT-5-3.9 – Microsystems and Smart Miniaturised Systems
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6
FIGURES
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FP7-ICT-2009-5 - Small or Medium-scale Focused Research Project
STREP: CP-FP-INFSO Heart-e-Gel 258909
ICT-5-3.9 – Microsystems and Smart Miniaturised Systems
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Figure 1: Schematic representation of the artificial circulation (1= roller pump; 2=
pneumatically driven ventricle; 3= compliance chamber, 4= test compartment; 5=
resistance; 6= heat exchanger; 7= reservoir; F= flow sensor: Pa, Pb= pressure sensor, S=
sonomicrometry).
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FP7-ICT-2009-5 - Small or Medium-scale Focused Research Project
STREP: CP-FP-INFSO Heart-e-Gel 258909
ICT-5-3.9 – Microsystems and Smart Miniaturised Systems
9
__________________________________________________________________________
FP7-ICT-2009-5 - Small or Medium-scale Focused Research Project
STREP: CP-FP-INFSO Heart-e-Gel 258909
ICT-5-3.9 – Microsystems and Smart Miniaturised Systems
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Figure 2: The compliance in the prerssure function for different amounts of air in the
Windkessel.
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FP7-ICT-2009-5 - Small or Medium-scale Focused Research Project
STREP: CP-FP-INFSO Heart-e-Gel 258909
ICT-5-3.9 – Microsystems and Smart Miniaturised Systems
11
Figure 3: View on the compliance chamber (A), the test compartment with latex aneurysm
model (B), flow sensor (C) and pressure transducers (D).
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FP7-ICT-2009-5 - Small or Medium-scale Focused Research Project
STREP: CP-FP-INFSO Heart-e-Gel 258909
ICT-5-3.9 – Microsystems and Smart Miniaturised Systems
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Figure 4: Examples of different latex vessel models which can be mounted within the test
compartment.
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FP7-ICT-2009-5 - Small or Medium-scale Focused Research Project
STREP: CP-FP-INFSO Heart-e-Gel 258909
ICT-5-3.9 – Microsystems and Smart Miniaturised Systems
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Figure 5: Test compartment for testing venous occlusion (1= hydrogel).
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FP7-ICT-2009-5 - Small or Medium-scale Focused Research Project
STREP: CP-FP-INFSO Heart-e-Gel 258909
ICT-5-3.9 – Microsystems and Smart Miniaturised Systems
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Figure 6: An example of arterial pressure and flow curves generated by the pulse duplicator.
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FP7-ICT-2009-5 - Small or Medium-scale Focused Research Project
STREP: CP-FP-INFSO Heart-e-Gel 258909
ICT-5-3.9 – Microsystems and Smart Miniaturised Systems
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Figure 7: Test compartment for testing arterial occlusion / arterio-venous connection (1=
hydrogel; 2= resistance; A= high pressure; B= low pressure).
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FP7-ICT-2009-5 - Small or Medium-scale Focused Research Project
STREP: CP-FP-INFSO Heart-e-Gel 258909
ICT-5-3.9 – Microsystems and Smart Miniaturised Systems
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Figure 8: Test compartment for testing aneurysmal sac occlusion (1= hydrogel; 2=
endoprosthesis).
7
REFERENCES
1.
Donovan FM, Jr. Design of a hydraulic analog of the circulatory system for evaluating artificial
hearts. Biomater Med Devices Artif Organs 1975; 3(4):439-49.
2.
Vermette P, Thibault J, Laroche G. A continuous and pulsatile flow circulation system for
evaluation of cardiovascular devices. Artif Organs 1998; 22(9):746-52.
3.
Schima H, Baumgartner H, Spitaler F, et al. A modular mock circulation for
hydromechanical studies on valves, stenoses, vascular grafts and
cardiac assist devices. Int J Artif Organs 1992; 15(7):417-21.
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FP7-ICT-2009-5 - Small or Medium-scale Focused Research Project
STREP: CP-FP-INFSO Heart-e-Gel 258909
ICT-5-3.9 – Microsystems and Smart Miniaturised Systems
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4.
Vandenberghe S, Segers P, Meyns B, Verdonck P. Hydrodynamic characterisation of ventricular
assist devices. Int J Artif Organs 2001; 24(7):470-7.
5.
Verdonck P, Kleven A, Verhoeven R, et al. Computer-controlled in vitro model of the human left
heart. Med Biol Eng Comput 1992; 30(6):656-9.
6.
Legendre D, Fonseca J, Andrade A, et al. Mock circulatory system for the evaluation of left
ventricular assist devices, endoluminal prostheses, and vascular diseases. Artif Organs 2008;
32(6):461-7.
7.
Liu Y, Allaire P, Wood H, Olsen D. Design and initial testing of a mock human circulatory loop for
left ventricular assist device performance testing. Artif Organs 2005; 29(4):341-5.
8.
Tamari Y, Lee-Sensiba K, Leonard EF, et al. The effects of pressure and flow on hemolysis caused
by Bio-Medicus centrifugal pumps and roller pumps. Guidelines for choosing a blood pump. J
Thorac Cardiovasc Surg 1993; 106(6):997-1007.
9.
Schima H, Muller MR, Tsangaris S, et al. Mechanical blood traumatization by tubing and throttles
in in vitro pump tests: experimental results and implications for hemolysis theory. Artif Organs
1993; 17(3):164-70.
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FP7-ICT-2009-5 - Small or Medium-scale Focused Research Project
STREP: CP-FP-INFSO Heart-e-Gel 258909
ICT-5-3.9 – Microsystems and Smart Miniaturised Systems
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