Note: Descriptions are shown in the official language in which they were submitted.
CA 02470150 2004-07-02
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TITIrE OF 'FI-IE IN'JEhITIOIrI
Selective Organ Hypothermia l~iethod rind Apparatus
This is a divisional of Canadian Patent Application 2,318,084 filed
January 21, I 999.
EACIt~iItOI_TNO OF THE INVEN'I"ION
s Field ~f the Invention - The current invention relates to selective cooling,
or
hypothermia, of an organ, such as the brain, by cooling the blood flowing into
the
~rgan. This cooling can protect the tissue from injury caused by anoxia or
trauma.
Eackground Information - Organs of the human body, such as the brain,
kidney, and heart, are maintained at a constant temperature of approximately
37° C.
Cooling of organs below 35° C is known to provide cellular protection
from anoxic
damage caused by a disruption of blood supply, or by traiuxta. Cof~ling can
also reduce
swelling associated with these injuries.
Hypothermia is currently utilized in mediciine and is sometimes performed t~
pr~tect the brain from injury. Cooling of the brain is generally acdcoplished
through
~ s whole body cooling to create a condition of total body hypothermia in the
range of 20°
to 30° C. This cooling is accomplished by immersing the patient in ice,
by using
cooling blankets, or by cooling the blood flowing externally through a .
cardiopulmonary bypass machine. TJ. S. Pat. No. 3,425,419 to I)ato and Z.J. S.
Pate No.
5,486,208 to Csinsburg disclose catheters for cooling the blood to create
total body
2o hypothermia However, they rely ora circulating a c~ld fluid to produce
cooling. This is
unsuitable for selective organ hypothermia, because cooli:r~g of tt~e entire
catheter by
the cold fluid on its way to the organ would ultimately result in non-
selective, or total
body, cooling.
Total body. hypothermia to provide organ protection has a number of
2s drawbacks. First, it creates cardiovascular problems, such as cardiac
arrhythmias,
reduced cardiac output, and increased systemic vascular eesistanee. These side
e~'ects
can result in organ damage. These side effects are believed, to be c~~used
reflexively in
response to the reduction in core body temperature. Seconst, total body
hypothermia is
difficult to administer. Irr~nersing a patient in ice water clearly has its
associated
3a problems. Placement ors cardiopulmonary bypass requires surgical
intervention and
specialists.to operate the machine, and it is associated with a number of
complications
including bleeding and volume overload. Third, the tine required to reduce the
body
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temperature and the organ temperature is prolonged. l~inimi2ing the ti~tae
between
injury and the onset of cooling has been shown to produce better clinical
outeomes.
Some physicians have in~rnersed the patient's head in ice to pmvide brain
cooling. There are also cooling helmets, or head gear, to perform the same.
This
5 approach suffers frogn the problems of slow cool down and poor temperature
control
due to the temperature gradient that must be established externally to
internally. It has
also been shown fleet complications associated with total body cooling, such
as
arrhythmia and decreased cardiac output, can also be caused by cooling of the
face
and head only.
to Selective organ hypothermia has been studied by Schwartz, et, at.
'lJtilizing
baboons, blood was circulated and cooled externally #~°oans the body
via the femoral
artery and returned to the body through the carotid artery. "This study showed
that the
brain could be selectively cooled to temperatures of 20° ~ without
reducing the
temperature of the entire body. Subsequently, cardiovascular complications
associated
IS total body hypothermia did not occur. However, external circulation of the
blood for
cooling is not a practical approach for the treatment of humans. The risks of
infection,
bleeding, and fluid imbalance are great. Also, at least two arterial vessels
must be
punctured and can..°zulated. Further, percutaneous cannulation of the
caroeid artery is
very difficult and potentially fatal, due to the associated arterial wall
trauma. Also,
2a this method could not be used to cool organs such as the kidneys, where the
renal
arteries cannot be directly cannulated pereutaneously.
Selective organ hypothermia has also been attempted by perfusing the organ
with a cold solution, such as saline or perflourocarbons. This is cozncnonly
done to
protect the heart during heart surgery and is refexred to as cardioplegia.
This procedure
~s has a number of drawbaclCS, including limited time of administration due to
excessive
volume accumulation, cost and inconvenience of maintaining the perfiasate, and
lack
of effectiveness due to temperature dilution from the blood. Temperature
dilution by
the blood is a particular problem in high blood flow organs such as the brain.
For
cardioplegia, the blood flow to the heart is minimized, and thei°efore
this effect is
30 minimized.
lntravascular, selective organ hypothermia, created by ~.,ooling the blood
flowing into the organ, is the ideal method. First, because only the target
organ is
2
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cooled, complications associated with total body hy';pothermia are avoided.
Second,
because the blood is cooled intravasculariy, or in situ, problems associated
with
external circulation of'blood are eliminated. Third, only a single puncture
and arterial
vessel cannulation is required, and it can be performed at an easily
accessible artery
s such as the femoral, subclavian, or brachial. Fourth, cold perfusate
solutions are not
required, thus eliminating problems with excessive fluid accumulation. This
also
eliminates the time, cost, and handling issues associated with providing and
maintaining cold per~usate solution. Fifth, rapid ccsoling can be achieved.
Sixth,
precise temperature contxol is possible.
o Previous inventors have disclosed the circulation of a cold fluid to produce
total body hypotherm$a, by placing a probe into a rna~or vessel of the body.
This
approach is entirely unfeasible when considering selective organ hypothermia,
as will
be demonstrated belo~~.
The important factor related to catheter development for selective organ
15 hypothermia is the small size of the typical feeding artery, and the need
to prevent a
significant reduction in blood flow when the catheter is placed in the artery.
h
significant reduction it blood flow would result in ischemic organ damage.
While the
diameter of the mayor ~~essels of the body, such as the vane cave and aorta,
are as large
as I 5 to 20 mm., the diameter of the feeding artery of an organ is typically
only 4.0 to
20 8.0 mm. Thus, a catheter residing in one of these arteries cannot be much
larger than
2.0 to 3.0 mm. in outside diameter. It is not practical, to con:.~aruct a
selective organ
hypothermia catheter of this small size using the circulation of cold water or
other
fluid. Using the brain as an example, this point will be illustrated.
The brain typically has a blood flow rate of approximately 500 to 7~0 cc/min.
2s Two carotid arteries feed this blood supply to the brain. The internal
carotid is a small
diameter artery that branches off of the common carotid near the angle of the
jaw. To
cool the brain, it is important to place some of the cooling portion of the
catheter into
the internal carotid artery, so as to mimimize cooling of the face via the
external
carotid, since face cooling can result in complications, as discussed above.
It would
3o be desirable to cool the blood in this artery down to 32°C, to
achieve the desired
cooling of the brain. T~ cool the blood in this artery by a SC° drop,
from 37°C down
to 32°C, requires between 100 and 150 watts ofrefrigeration po~~rer.
3
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In order to reach the internal carotid artery from a femoral insertion point,
an
overall catheter length of approximately 100 cm. would be required. To avoid
undue
blockage of the blood flow, the outside diameter of the catheter can not
exceed
approximately 2 mm. Assuming a coaxial construction, this limitation in
diameter
5 would dictate an internal supply tube of about 0.70 nlan. diameter, with
return flow
being between the internal tube and the external tube.
A catheter based on the circulation of water or saline operates on the
principle
of transferring heat frogs the blood to raise the temperature of the water.
Rather than
absorbing heat by boiling at a constant temperature like a freon, water must
warm up
~ o to absorb heat and produce cooling. f~Iater flowing at the rate ~~f 5.0
gramslsec, at an
initial temperature of 0°C and warming up to 5°C, can absorb 100
watts of heat. Thus,
the outer surface of the heat transfer element could onl~r '~ maintained at
5°C, instead
of 0°C. This will require the heat transfer element to have a surface
area of
approximately 1225 °n2. If a catheter of approximately 2.0 mm. diameter
is
1 s assumed, the length of the heat transfer element would have to be
approximately 20
cm.
In actuality, because of the overall length of the catheter, the water would
undoubtedly warrra up before it reached the heat transfer element, and
provision of
0°C water at the heat transfer element would be impossible. Circulating
a cold liquid
2o would cause cooling along the catheter body and could result ire
nonrspecific or total
body hypothermia. Furthermore, to achieve this heat transfer rate, 5
gratnslsec of
water flow are required. To circulate water through a 100 cm. long, 0.70 mm.
diameter supply tube at this rate produces a pressure dr~~p of more than 3000
psi. This
pressure exceeds the safety levels of many flexible medical g~°ade
plastic catheters.
25 Further, it is doubtful whether a water pump that can .generate these
pressures and
flow rates can be placed in an operating room.
~I~IEF SUMMARY ~F THE 1NVT"lrlTI~N
The selective organ cooling achieved by the present invention is accomplished
30 by placing a cooling catheter into the feeding artery of the organ. The
cooling catheter
is based on the vaporization and expansion of a compressed and condensed
refrigerant, such as freon. In the catheter, a shaft or t~ody section would
carry the
4
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liquid refrigerant to a distal heat transfer element where vaporization,
expansion, and
cooling would occur. Cooling of the catheter tip to temperatures above minus
~°C
results in cooling of the blood flowing into the organs located distally of
the catheter
tip, and subsequent cooling of the target organ. For example, the catheter
could be
placed into the internal carotid artery, to cool the brain. The ;size and
location of this
artery places significant demands on the size and flexibility of the catheter.
Specifically, the outside diameter of the catheter must be minimized, so that
the
catheter can fit into the artery without compromising blood flow. Art
appropriate
catheter for this application would have a flexible body of l0 to 100 cm. in
length and
t0 2.0 to 3.0 mm. in outside diameter.
It is important for the catheter to be flexible in order to successfully
navigate
the arterial path, and this is especially true of the dish end of the
catheter. So, the
distal end of the catheter must have a flexible heat transfer element, which
is
corr'posed of a material which conducts heat better than the remainder of the
catheter.
The catheter body material could be nylon or f~A?C;, and the heat transfer
element
could be madc from nitinol, which would have approximately 70 to I00 times the
thermal conductivity of the catheter body material, and whir>h is also
superelastic.
Nitinol could also be treated to undergo a transition to another shape, such
as a coil,
once it is placed in the proper artery. Certain tip shapes =~.ould improve
heat transfer as
well as allow the long tip to reside in arteries of shorter length.
The heat transfer element would require sufficiaent surface area to absorb 100
to i 50 watts of heat. This could be accomplished with a 2 mm, diameter heat
transfer
tube, 15 to 18 cm, in length, with a surfacx temperature of 0°C. Fins
can be added to
increase the surface area, or to maintain the desired surfhce area while
shortening the
2s length.
The cooling would be provided by the vaporization anal expansion of a: liquid
refrigerant, such as a freon, across an expansion element, such ~a a capillary
tube. For
example, freon 1112 boiling at 1 atmosphere and a flow rate of between 0.11
and O.18
liter/sec could provide between approximately 100 grad I50 watts of
refrigeration
power. Utilizing a liquid refrigerant allows the cooling to be focused at floe
heat
transfer element, thereby eliminating cooling along tire catheter body.
Utilizing
boiling heat transfer to the expanded fluid also lowers the fluid flow rate
requirement
5
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76927-17B
to remove the n oust of beat fronn the b! This ~ iru the
required small diameter of the catheter would have higher ~ drops at higher
ilo~nr rates:
The catheter dvould be bunt in a coaxiaD c~nstruction with a 0.70 nam. leaner
would be connected to the !ow pressure side of the cozaa r.
Thus, in a broad aspect9 the invention provides an apparatus for causing
hypothermia in at least a portion o~° a mammal, said apparatus
comprising: a
source of working fiuid~ a flexible elongated catheters said catheter having a
flexible tubular outer catheter body; a flexible tubular inner working fluid
supply
conduit located within said outer catheter body, a proximal end of said inner
working fluid supply conduit being connected in fluid flor~~ communication
with
6
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?6927-17D
an outlet of said source of working fluid; a working fluid
return path within said outer catheter body a proximal end
of said working fluid return path being connected in fluid
flow communication with an inlet of saint soixrce of working
fluid; a flexible elongated, hollow, heat transfer element
mounted to said distal end of said outer catheter body; and
a chamber defined within said hollow heat transfer element,
said chamber being connected in fluid flow communication
with an outlet of said working fluid supply conduit, said
chamber being connected in fluid flow coimxnurr.ication with a
distal end of said working fluid return path wa.thin said
outer catheter bodyo
'Ihe novel features of this invention, as well as
the invention itself, will be best understood from the
attached drawings, taken along with the following
description, in which similar reference characters _refer to
similar parts, and in which:
BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS
Figure 1 is a schematic, partially in section,
showing a. first embodiment of the flexib~.e catheter
according to the present invention.
6a
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F n ~ ~ , ./~"..
CVO 99t37a26 ~'~TIiJS99lOd275
Figure 2 is a perspective view of a second etrabodirraent of the distal tip of
the
catheter of the present invention, after uansforntation;
Figure 3 is a section view of a third embodiment of the distal tip of the
catheter
of the present invention, after expansion of the heat transfer element;
Figure 4 is a partial section view ofa fourth etrtboditxtent of the distal tip
of the
catheter of the present invention, after transformation;
Figure 5 is an elevation view of a fifth embodiment of the distal tip of the
catheter of the present invention, before transformation.,
Figure 6 is an elevation view of the embodiment shown in Figure 5, after
t o transformation to a double helix;
Figure 7 is an elevation view of the emboditrtent shown in Figure 5, after
transformation to a loops:d coil;
Figure 8 is an elevation view of a sixth embodiment of the distal tip of the
catheter of the present invention, showing longitudinal fins on the heat
transfer
i 5 element;
Figure 9 is an end view of the embodiment shown in Figure 8;
Figure 10 is an elevation view of a seventh embodiment of the distal tip of
the
catheter of the present invention, showing annular fins on the heat transfer
element;
and
2o Figure 1 l is an end view of the embodiment shove in Figure 10.
DETAIarED I~ESCFtIPTION OF THE IN'JENT.ION
As shown in Figure 1, the apparatus of the present invention includes a
flexible catheter assembly 10, fed by a refrigeration coanpressor unit 12,
which can
z5 include a condenser. The compressor unit 12 has an outlet 14 and an inlet
16. The
catheter assembly 10 has an outer flexible catheter body 18, which can be made
of
braided P13AX or other suitable catheter material. The catheter body 18 must
be
flexible, to enable passage through the vascular system of the patient to the
feeding
artery of the selected organ. The inner lumen 19 of the catheter body 18
serves as ehe
30 return flow path for the expanded refrigerant. The catheter assetr~bly 10
also has an
inner flexible refrigerant supply conduit 2b, which can be made of nylon,
polyimide,
nitinol, or other suitable catheter material. The length anal diarne~ter of
the catheter
7
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body 18 and refrigerant supply conduit 20 are designed for the size and
location of the
artery in which the apparatus will be used. For use in tlxe internal carotid
artery to
achieve hypothermia of the brain, the catheter body 18 and refrigerant supply
conduit
20 will have a length of approximately 'JO to 100 centimeters. The catheter
body 18
for this application will have an outside diameter of approximately 2.5
millimeters
and an inside diameter of approximately 2.0 millimeters, and the refrigerant
supply
conduit will have an outside diameter of approximately 1.0 rraillimeter and an
inside
diameter of approximately 0.7~ millimeter. A supply conduit 20 of this
diameter will
have a refrigerant pressure drop of only approximately 0.042 atmospheres per
100
centimeters. The return flow path through a catheter body 1 ~3 of this
diameter will
have a refrigerant pressure drop of only approximately 0.064 atmospheres per
100
centimeters.
The compressor outlet I4 is attached in fluid flow comi:nunication, by known
means, to a proximal end of the refrigerant supply c.oraduit '20 disposed
coaxially
t 5 within said catheter body 18. The distal end of the refrigerant supply
conduit 20 is
attached to an expansion element, which in this embodiment is a capillary tube
22
having a lenght of approximately i 5 to 2~ centimeters. '1°he capillary
tube 22 can be
made of polyimide or nitinol, or other suitahle material, and it can be a
separate
element attached to the supply conduit 20, or it can be an integral portion of
the
20 supply conduit 20. For the internal carotid artery application, the
capillary tube 22
will have an outside diameter of approximately 0.6 millgrraeter arad an inside
diameter
of approximately 0.25 millimeter. The expansion element, such as the capillary
tube
22, has an outlet wtthan a Chamber Of a flexible heat transfer element such as
the
hollow flexible tube 24. The tube 24 shown in this embodiment is flexible but
25 essentially straight in its unflexed state. The heat transfer element must
be flexible, to
enable passage through the vascular system of the patient o the i:eeding
artery of the
selected organ. For the internal carotid application the i'Iexible tube 24
will have a
tength of approximately 1 S eentameters, an outside diameter of approximately
1.9
millimeters and an inside diameter of approximately l..S millimeters. The heat
3o transfer element also includcs a plug 26 in the distal end of the flexible
tube 24. The
plug 26 can be epoxy potting material, plastic, or a metal such as stainless
steel or
CA 02470150 2004-07-02
W~ 9913'7226 hCTNS99/Ot275
gold. A tapered transition of epoxy potting material can be provided between
the
catheter body 18 and the flexible tube 24.
A refrigerant, such as freon, is compressed, condensed, and pumped through
the refrigerant supply conduit 20 to the expansion elemaent, or capillary
tube, 22. The
5 refrigerant vaporizes and expands into the interior chamber of the heat
transfer
element, such as the flexible tube 24, thereby cooling the heat transfer
element 24.
Blood in the feeding artery flows around the heal transfer element 24, thereby
being
cooled. The blood then continues to flow distally into the selected organ,
thereby
cooling the organ.
to A second embodiment of the heat transfer element is shown in Figure 2. This
embodiment can be constructed of a tubular material such as nitinol, which has
a
temperature dependent shape memory. The heat transfer element 28 can be
originally
shaped like the flexible tube 24 shown in Figure I, at room
tempea°ature, but trained to
take on the coiled tubular shape shown in Figure 2 at a lower temperature.
This
t 5 allows easier insertion of the catheter assembly 10 through the vascular
system of the
patient, with the essentially straight but flexible tubular shape, similar to
the flexible
tube 24. Then, when the heat transfer element is at the desired location in
the feeding
artery, such as the internal carotid artery, refrigerant .flow is commenced.
As the
expanding refrigerant, such as a 50/50 mixture of pentafluoroethane and l,I,l
2o trifluoroethane or a SOI~O mixture of difluoromethane and
per~tafluoroethane, cools
tine heat transfer element down, the heat transfer elemeaat takes on the shape
of the
heat transfer coil 28 shown in Figure 2. This enhances the heat transfer
capacity,
while limiting the length of the heat transfer element.
A third embodiment of the expansion element and the heat transfer element is
25 shown in Figure 3. This eanbodiment of the expansion eierrtent is an
orifice 30, shown
at the distal end of the refrigerant supply conduit 20. The outlet of the
orifice 30
discharges into an expansion chamber 32. In tnis embodiment, the heat transfer
element is a plurality of hollow tubes 34 leading from ties expansion chamber
32 to
the refrigerant return lumen 19 of the catheter body 18. 'Chis embodiment of
the heat
3o transfer element 34 can be constrtacted of a tubular material such as
nitinol, which has
a temperature dependent shape memory, or some other tubular material having a
permanent bias toward a curved shape. The heat transfer element tubes 34 can
be
9
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w~ 99137226 PC:TlUS99/01275
essentially straight, originally, at room temperature, but trained to take on
the
outwardly flexed "basket" shape shown in Figure 3 at a lower temperature.
'this
allows easier insertion of the catheter assembly 10 through the vascular
system of the
patient, with the essentially straight but flexible tubes. Then, when the heat
transfer
s element 34 is at the desired location in the feeding artc;ry, suct°~
as the internal carotid
artery, refrigerant flow is commenced. As the expanding refrigerant cools the
heat
transfer element 34 down, the heat transfer element takes on the basket shape
shown
in Figure 3. This enhances the heat transfer capacity, while limiting the
length of the
heat transfer element.
A fourth errrbodiment of the heat transfer elemene is shown in Figure 4. This
embodiment can be constructed of a material such as nitinol. The heat transfer
element 36 can be originally shaped as a long loop extending from the distal
end of
the catheter body 1 g, at room temperature, but trained to take on the coiled
tubular
shape shown in Figure 4 at a tower temperature, with, the heat transfer
element 36
t 5 coiled around the capillary cube 22. 'This allows easier insertion of the
catheter
assembly 10 through the vascular system of the patient, with the essentially
straight
but flexible tubular loop shape. Then, when the heat transfer element 36 is at
the
desired location in the feeding artery, such as the internal carotid artery,
refrigerant
flow is commenced. A.s the expanding refrigerant cools the :heat transfer
element
2o down, the heat transfer element takes on the shape of the coil 35 shown in
Figure 4.
This enhances the heat transfer capacity, while limiting the length of the
heat transfer
element 36. Figure 4 further illustrates that a thermocouple 3& can be
incorporated
into the catheter body I li for temperature sensing purpos~a.
Yet a fifth embodiment of the heat transfer element is shown in Figures 5, 6,
2s and 7. In this embodiment, an expansion element, such as a capillary tube
or oaifice,
is incorporated within the distal end of the 6;atheter body I$. This
embodiment of the
heat transfer element can be constructed of a rraaterial such as nitirtol. The
heat
transfer element is originally shaped as_a long Loop 40 extending from the
distal end of
the catheter body 1 g, at roorrt temperature. The long loon 40 has two sides
42, 44,
3o which are substantially straight but flexible at morn temperatzare. The
sides 42, 44 of
the long loop 40 can be trained to take on the double helical shape shown in
Figure 6
at a lower temperature, with the two sides 42, 44 of the heat transfer element
40 coiled
CA 02470150 2004-07-02
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W~ 99137226 PCTJtJS99/OI275
around each other. Alternatively, the sides 42, 44 of the long loop 40 can be
trained to
take on the looped coil shape shown in Figure 7 at a lower temperature, with
each of
the two sides 42, 44 of the heat transfer element 40 coiled independently.
Either of
these shapes allows easy insertion of the catheter assembly 10 through the
vascular
s system of the patient, with the essentially straight but flexible tubular
loop shape.
Then, when the heat transfer element 40 is at the desirc;d location in the
feeding artery,
such as the internal carotid artery, refrigerant flow is commenced. As the
expanding
refrigerant cools the heat transfer element down, the heat transfer element 40
takes on
the double helical shape shown in Figure 6 or the looped coil shape shown in
Figure 7.
to Both of these configurations enhance the heat transfer capacity, while
limiting the
length of the heat transfer element 40.
As shown in figures 8 through 11, the heat transfer element 24 can have
external fins 46, 48 attached thereto, such as by welding or brazing, to
promote heat
transfer. Use of such fins allows the use of a shorter heat trftnsfer element
without
~ 5 reducing the heat transfer surface area, or increases the heat transfer
surface area for a
given length. In Figures 8 and 9, a plurality of longitudinal fins 46 are
attached to the
heat transfer element 24. The heat transfer element 24 in such an embodiment
can
have a diameter of approximately I .0 millimeter, while each of the fins 46
can have a
width of approximately 0.5 millimeter and a thiclrness of approximately 0.12
20 millimeter. This will give the heat transfer element an overall diameter of
approximately 2.0 millimeters, still allowing the cathebter to be inserted
into the
internal carotid artery.
in Figures 10 and I1, a plurality of annular fins 4g are attached to the heat
transfer element 24. "The heat transfer element 24 in such an embodiment can
have a
25 diameter of approximately 1.0 millimeter, while each of the 4g can have a
width
of approximately 0.5 millimeter and a thickness of approximately 0.12
millimeter.
This will give the heat transfer element an overall diameter of approximately
2.0
millimeters, still allowing the catheter to be inserted into the internal
carotid artery.
3o While the particular invention as herein shown and disclosed in detail is
fully
capable of obtaining the ob,~ects and providing the advantages her~.inbefore
stated, it is
to be understood that this disclosure is merely illustrative of the presently
preferred
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embodiments of the invention and that no limitations are intended other than
as
described in the appended claims.
12
