Lecture Six
*Artificial Organs 2 *
Dr. Waleed Jasim
The Lung and Its Transplantation and Artificial Replacement
The human thoracic cavity houses a pair of lungs, the left lung and the
right lung. The left lung is slightly smaller (since the heart is placed a bit to
the left in the body) and has two lobes, and the right lung is bigger, with three
lobes. They are spongy and elastic organs that are broad at the bottom and
taper at the top. They consist of air sacs, the alveoli. Many alveoli group
together and open into a common space. From this space arise the alveolar
ducts, which join together to form bronchioles. The bronchioles connect them
to the respiratory tract. The lungs also have blood vessels, the branches of the
pulmonary artery and veins
Gaseous Exchange
The capillaries lining the alveoli have blood that has a low concentration of
oxygen. So the oxygen from the air easily diffuses into the blood through the
thin barrier of the alveolus wall. Similarly, since the concentration of carbon
dioxide is quite high in the blood, the gas easily diffuses out into the alveolar
space. From here, the air which has a comparatively higher concentration of
carbon dioxide than the air that entered it leaves the lungs
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Lecture Six
*Artificial Organs 2 *
Dr. Waleed Jasim
Design of Artificial Lungs
Potkey of VAMC Cleveland, Ohio (2009), recently developed one model
of artificial lungs. Artificial lungs mimic the function of real lungs, adding
oxygen to, and removing carbon dioxide from, the blood. The human lung is a
remarkable organ, providing a maximum gas exchange rate for both O2 and
CO2 of 2–6 l/min. On the other hand, current artificial lungs are only capable
of a maximum gas exchange rate of 0.25–0.40 l/min, limiting their use to the
short-term respiratory support for patients at rest. This insufficiency is due to
the smaller surface area, smaller surface-area-to-volume ratio, and greater
membrane thickness of artificial lungs compared to the human lung. Recent
advances in the micromachining of silicone elastomer (PDMS) have made
possible the creation of a new highly efficient artificial lung (Fig.) with
feature sizes similar to or better than those of the human lung. Such a
micromachined artificial lung would have
an improved gas exchange performance
compared to its conventional counterparts,
potentially resulting in increased clinical use.
Design Overview
Silicone has been used as the membrane material in some commercially
available artificial lungs due to its biocompatibility, durability, stability, and
high permeability to oxygen and carbon dioxide. However, these devices have
limited gas-exchange capability mainly due to the membrane’s thickness (>50
μm). A significant advantage of silicone membranes is that blood plasma
leakage does not occur as it does in microporous hollow fiber oxygenators. In
fact, hollow fiber oxygenators are sometimes coated with a thin layer of
silicone in order to reduce plasma leakage and increase the device lifetime.
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Lecture Six
*Artificial Organs 2 *
Dr. Waleed Jasim
Design of an Implantable Artificial Lung
* Basic Features
The design specifications of an implantable artificial lung are outlined in
Table
 -Capable of transferring > 200 ml/min of oxygen and carbon dioxide
 -Blood flow pattern resulting in efficient gas transfer and minimal shunting
 -Blood-side pressure loss < 15 mm Hg at blood flow rates (cardiac output) of 4-6
l/min
 -Gas-side pressures less than blood-side pressures to avoid gas embolism
 -Compliant housing chamber or connecting tubing to minimize impedance to
 pulsatile blood flow
 -Reliability and durability to function at unaltered performance for at least 2-3
weeks
 -Size and configuration to fit in the hemithorax without impingement of
surrounding structures
 -Thromboresistant and otherwise biocompatible
Utilizing currently available materials as
the gas exchange surface, the implantable
artificial lung that is compact, yet
efficient, is composed of a bank of hollow
fibers (e.g., microporous polypropylene)
across which flows the blood and through
which flows the oxygenating gas (Fig).
This cross-flow configuration, as long as the blood channels are not too
wide and the blood path is tortuous, ensures good convective mixing at the
boundary layer between blood and the fiber surface. The fiber bundle is
encased in a housing material that optimally is nonreactive and will not erode
into surrounding structures in the thoracic cavity. Blood enters the housed
bundle, oxygenation and carbon dioxide removal occur as the blood passes
through the fiber bank, and the oxygenated blood exits the fiber bundle on the
opposite side. The fibers are potted at either end with a polyurethane-based
compound that serves to keep the fibers together and to separate the gas and
blood phases. The oxygenating gas enters a manifold at one end, distributes
and flows through the lumens of the hollow fibers, enters a manifold at the
other end, and exits. There are, therefore, four attachments to the artificial
lung: two blood lines for the inlet (deoxygenated blood) and outlet
(oxygenated blood), and two gas lines. The inlet and outlet blood lines may be
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Lecture Six
*Artificial Organs 2 *
Dr. Waleed Jasim
entirely intrathoracic, anastomosed, for example, to the proximal and distal
pulmonary artery. The gas lines, on the other hand, are extracorporeal, exiting
the thoracic cavity through the chest wall. The inlet gas is generally 100% O2
to achieve maximum oxygen transfer through the device. The exit gas line, up
to now, has also been extracorporeal, but conceivably could be intrathoracic if
a connection between a bronchus or the trachea was surgically established.
** Gas Exchange
The absolute transfer rate of oxygen and carbon dioxide through the artificial
lung is dependent on a number of factors:
1. The degree of convective mixing achieved in the blood phase, which is dependent on
the particular configuration and orientation of the fiber bundle;
2. Gas exchange surface area of the fiber bundle;
3. Blood flow rate through the device;
4. Characteristics of the blood itself, such as hemoglobin concentration, viscosity,
oxyhemoglobin saturation, and carbon dioxide content;
5. Fiber length or gas flow rate through the fiber bundle; and
6. Composition of the oxygenating and ventilating gas.
In order to maximize gas exchange, it is critical to achieve excellent
convective mixing of the blood as it passes through the fiber bundle of the
artificial lung. The designer of artificial lungs has several parameters that may
be manipulated to achieve excellent gas transfer and maintain low blood side
pressure losses. Consider blood flowing perpendicular to a bank of uniform
fibers of outer diameter d. The frontal area, Af, is the product of the overall
height, H, and the width, W. The overall length of the fiber bank in the blood
flow direction is L.
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Lecture Six
*Artificial Organs 2 *
Dr. Waleed Jasim
*** Hemodynamic Compatibility
In addition to adequate gas exchange capability, the artificial lung must be
hemodynamically compatible with the cardiovascular system.
Two approaches may be followed:
- The artificial lung derives its blood flow directly from the heart, thereby
avoiding the need for an external, mechanical blood pump, and a composite
artificial heart-lung system may be devised, incorporating a mechanical pump
to provide blood flow through the lung.
- - The latter approach has been taken by Japanese investigators, who have
used a pneumatically driven blood pump to generate the pressure to force
blood through the hollow fiber artificial lung. The advantages of having an
incorporated blood pump are that the blood-side pressure losses across the
lung become less of a design issue and adequate blood flows are easily
achieved.
On the other hand, the addition of a blood pump to the lung introduces
another level of complexity to the device, makes the device less compact,
increases the potential for mechanical device failure, and is associated with
higher rates of thromboembolism and direct trauma to the blood elements.
**** Biocompatibility
The biocompatibility of any artificial organ must be considered in its design.
Both material-specific and device-specific factors should be accounted for.
Silicone rubber and microporous polypropylene have proven to be the best
materials for artificial lungs because of their high diffusivities for CO2 and
O2. Hollow fibers made of polypropylene are currently the industry standard
for manufacturing membrane oxygenators because of the small diameter and
compactness that can be achieved, thus this material has emerged as the
choice for artificial lung development, as well. Moreover, a higher gas transfer
rate per unit of surface area may be achieved with microporous polypropylene
than with silicone rubber.
A disadvantage of the microporous polypropylene is that plasma leakage
into the gas phase may occur over time. This results in impaired gas exchange
and device failure. In order to prevent plasma leakage, chemical modification
or surface coating of the fibers is recommended. Surface coating with a thin
silicone-based membrane was used for the intravascular oxygenator (IVOX),
and is being actively investigated for application to the implantable artificial
lung.
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Lecture Six
*Artificial Organs 2 *
Dr. Waleed Jasim
In Vitro Evaluation
In vitro evaluation of prototype artificial lung devices allows for the tight
control of operating conditions and precise measurement of pressure losses
and oxygen and carbon dioxide transfer rates. In vitro tests have been
conducted in both water and in animal blood. Testing the artificial lungs in
water permits multiple evaluations to be performed on a single device and is
much easier to accomplish than testing the devices in blood. In order to
correlate artificial lung performance in water with that in blood, we developed
a semi-empirical mathematical model of oxygen transfer that allows us to
predict the oxygen transfer rate to blood at any set of operating conditions,
based on the results of in vitro water tests
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Lecture Six
*Artificial Organs 2 *
Dr. Waleed Jasim
Engineering Design of Thoracic Artificial Lungs
Acute and chronic respiratory insufficiency continue with high mortality
rates. Ventilators, the common mode of therapy for acute episodes, and
oxygen supplies, the common mode of therapy for chronic conditions, are
effective in the majority of cases but are ineffective and even damaging in
many cases. Other current experimental approaches include liquid ventilation,
extracorporeal membrane oxygenation, extracorporeal carbon dioxide
removal, intravascular lung assist devices, and thoracic artificial lungs
(TALs).
General Design Considerations
Four general design aspects must be considered for any artificial organ:
function, hemodynamic compatibility, hematologic compatibility, and size and
shape. The following is a discussion of an engineering methodology for
designing thoracic artificial lungs.
The general strategy, however, should be applicable to designing all bloodbearing artificial organs. The function of most importance for an artificial lung
is the ability of the device to transfer oxygen and carbon dioxide to and from
blood, respectively, at rates that are dictated by the medical condition. If the
artificial lung is inadequate in gas transfer, other design aspects are moot. At
basal conditions, the average human has a blood flow rate of about 5 l/min
and requires oxygen to be supplied at a rate of about 260 ml/min and carbon
dioxide to be removed at a rate of about 200 ml/min.
The artificial lung must transfer these gases at these rates, as a minimum, if
the natural lung is not functioning at all. If the device is to be used as an assist
to a partially functioning lung, however, lesser rates may be effective. Unless
the need is for the device to supply at least half of the basal rates, its use
probably could not be justified.
The required power output of the right ventricle depends on the attachment
mode, the condition of the natural lung, and the design of the device. Because
the right ventricle operates in a pulsatile mode, the artificial lung, like the
natural lung, must be designed to have both a low resistance and large
compliance. A low resistance lowers pressure drop and, therefore, lowers
pulmonary arterial pressures, resulting in lower right ventricular work during
the entire cardiac cycle. A large compliance smoothes the blood flow pulse,
delivering a greater portion of the flow to the resistance during lower pressure.
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Lecture Six
*Artificial Organs 2 *
Dr. Waleed Jasim
Blood flow through any artificial organ is well-known to stimulate and
even lyse cells, and to activate the coagulation, clot lysis, and inflammatory
systems. Stimulation of thrombocytes and leukocytes and activation of the
intrinsic coagulation and complement systems are of particular interest. This
blood trauma is known to be due to two mechanisms:
(i) Abnormally high shear stresses, shear-induced trauma
(ii) Reactions with non-biologic synthetic materials, material-induced trauma.
The effects of high shear stress are known to depend not only on the
magnitude of the shear but also on how long the blood is exposed to the shear.
Very high stress is well tolerated if it exists for very short times, e.g., for a few
milliseconds. Low shear stress, on the other hand, can cause blood trauma if
sustained for long times, e.g., for a few seconds. The blood flow path through
most current artificial lungs is tortuous, with complicated, time-varying shear
stress.
The device, in addition to not requiring too much volume, needs to have a
shape that would be suitable for implant. The shape of the bundle should not
be too cube-like nor too flat, for ease of fit with the anatomic structures. The
overall shape can be assumed to be a rectangular box, having a frontal area, Af,
and blood path length, L, (i.e., bundle thickness).
The blood enters the bundle perpendicular to the frontal area and flows
through the bundle thickness. The blood path length should be relatively short
so the resistance to blood flow is small. The aspect ratio should be somewhere
in the range of 2:1 to 5:1. For a given set of specified constraints, the goal is to
optimize the fibre bundle with respect to size, shape, surface area, and flow
characteristics
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Lecture Six
*Artificial Organs 2 *
Dr. Waleed Jasim
Specific Design Considerations
Thoracic artificial lungs must be designed to meet requirements for
1. oxygen and carbon dioxide transfer,
2. resistance and compliance,
3. blood trauma, and
4. size and shape.
They are constrained by the
1. patient’s blood characteristics and
2. available technology and materials.
These devices will have two basic mechanical elements: the resistive
element or fibre bundle, where the gas exchange takes place, and the
compliant element.
Design: Gas Transfer and Fluid Mechanics
The gas transfer and fluid mechanical aspects of the typical design problem
would be to specify, depending on the specific pathology, the desired rates of
oxygen and carbon dioxide transfer, blood flow rate through the device and
required resistance and compliance of the device. Another specification for a
particular design would be the outlet PO2. The blood flow rate to be diverted
through the device could range from the total expected maximum cardiac
output to some fraction thereof. The ability of the device to transfer oxygen
depends on having access to a sufficient amount of blood. Transferring
oxygen to blood that already has saturated hemoglobin, although possible, is
very inefficient, thus the design should be such that exiting hemoglobin is
saturated but with little excess oxygen in dissolved form.
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Lecture Six
*Artificial Organs 2 *
Dr. Waleed Jasim
The flow through such a bundle of fibres is akin to flow through a packed bed,
and the pressure drop for flow through a packed bed is typically written as
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