U.S. patent number 3,914,954 [Application Number 05/285,739] was granted by the patent office on 1975-10-28 for procedure for conservation of living organs and apparatus for the execution of this procedure.
Invention is credited to Roland Karl Doerig.
United States Patent |
3,914,954 |
Doerig |
October 28, 1975 |
Procedure for conservation of living organs and apparatus for the
execution of this procedure
Abstract
Apparatus and process are provided for the conservation of
living organs by using a cooled perfusing means enriched with a
respiratory gas in a thermally insulated receptacle with a pumping
device driven by a gas and which regulates the perfusing medium
according to the flow-resistance in the organ.
Inventors: |
Doerig; Roland Karl (CH-8037
Zurich, CH) |
Family
ID: |
25695571 |
Appl.
No.: |
05/285,739 |
Filed: |
September 1, 1972 |
Foreign Application Priority Data
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Sep 2, 1971 [CH] |
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13000/71 |
Mar 24, 1972 [CH] |
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4479/72 |
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Current U.S.
Class: |
435/284.1;
62/384; 62/306 |
Current CPC
Class: |
A01N
1/0247 (20130101); A01N 1/0289 (20130101) |
Current International
Class: |
A01N
1/02 (20060101); B01F 003/04 () |
Field of
Search: |
;62/384,304,306 ;128/1R
;195/1.7 |
References Cited
[Referenced By]
U.S. Patent Documents
Primary Examiner: O'Dea; William F.
Assistant Examiner: Capossela; Ronald C.
Attorney, Agent or Firm: McGlew and Tuttle
Claims
What we claim is:
1. Apparatus for conservation, storage and transfer of living
organs which comprises a perfusion medium for carrying respiratory
gas under pressure to said living organs, an organ chamber having
one-way valve means for flow of said perfusion medium into the
organ chamber, conduit means for connecting said living organ to
said one-way valve means, check-valve means for the passage of said
perfusion medium containing respiratory gas therethrough from said
organ chamber, a pump chamber having gas inlet means for directing
respiratory gas into said pump chamber, vent means for venting gas
from said pump chamber, including pressure sensitive valve means
connected to said pump chamber for venting gas therefrom when the
pressure in said pump chamber reaches a predetermined level whereby
said perfusion medium is adapted to be circulated through said
living organ in said organ chamber by the pressure of said
respiratory gas in said pump chamber.
2. The apparatus according to claim 1, wherein said vent means is
disposed adjacent said gas inlet means, including a vent passage
with a flexible diaphragm therein having a flow opening
therethrough, an adjustable valve member having a valve surface
adapted to rest against said diaphragm to close said opening, said
diaphragm being flexible under pressure to move away from the valve
surface and open a passage therethrough and regulate the size of
the opening of said passage.
3. The apparatus according to claim 1 wherein said apparatus
includes filtering means for cleaning the perfusion medium.
4. The apparatus according to claim 1, wherein said apparatus
includes an outer top wall, an outer bottom wall and at least one
outer side wall, and said pump chamber is disposed in said
apparatus adjacent said organ chamber and separated therefrom by an
inner partition wall connected to said top wall and substantially
parallel to said side wall, said pump chamber has an inner bottom
wall connected to said inner partition wall and said outer said
wall, said one-way valve means is disposed in said inner partition
wall, and said conduit means for connecting said living organ to
said one-way valve means has a bladder connected thereto for
relieving pressure therein, said check-valve means is disposed in
said inner bottom wall of said pump chamber, and filter means are
disposed between said check-valve means in said inner bottom wall
and said outer bottom wall of said apparatus for cleansing
perfusion medium after circulation through said living organ
therein.
5. The apparatus according to claim 1, wherein said apparatus has
an outer top wall, an outer bottom wall, and at least one side
wall, and said pump chamber is disposed in said apparatus beneath
said organ chamber and separated therefrom by an inner partition
wall connected to said side wall and substantially parallel to said
bottom wall, a platform mounted in said organ chamber for
supporting said living organ therein, said one-way valve means is
mounted between said inner partition wall and said platform,
conduit means for connecting said living organ to said one-way
valve means, said check-valve means is disposed at said inner
partition wall in said pump chamber, and filter means are disposed
between said check-valve means and said one-way valve-means for
cleaning perfusion medium after circulation through said living
organ therein, said gas inlet means is adjustably mounted in said
inner partition wall, at least one vent passage is provided in said
inner partition wall adjacent said gas inlet means,
pressure-sensitive valve means supported on a movable spring member
are provided for closing said gas inlet means when pressure in said
organ chamber reaches a predetermined level, an elastic membrane is
disposed in said organ chamber covering said gas inlet means and
said vent passage including said flexible diaphragm.
6. The apparatus according to claim 1, wherein said vent means for
venting gas from said pump chamber includes a valve tube mounted in
the top of said chamber, a gas outlet in said tube outside said
pump chamber, a magnet member mounted at the end of said tube
outside said pump chamber, a valve bolt slidably mounted within
said tube, said bolt having a magnetizable valve holding plate
attached to the end of said bolt outside said pump chamber for
closing said valve tube.
7. Apparatus for conservation, storage and transfer of living organ
which comprises a perfusion medium for carrying respiratory gas
under pressure to said living organ, an organ chamber having
one-way valve means for flow of said perfusion medium into the
organ chamber adapted to contain said perfusion medium, air inlet
means for introducing air into said organ chamber beneath the
surface of said perfusion medium and air outlet means for venting
air from said organ chamber above the surface of said perfusion
medium, conduit means for connecting said living organ to said
one-way valve means, check-valve means for the passage of said
perfusion medium containing respiratory gas therethrough from said
organ chamber, a pump chamber having gas inlet means for directing
gas into said pump chamber, vent means for venting gas from said
pump chamber including a vent passage with a flexible diaphragm
therein having a flow opening therethrough, an adjustable valve
member having a valve surface adapted to rest against said
diaphragm to close the opening, said diaphragm being flexible under
pressure to move away from the valve surface and open a passage
therethrough and regulate the size of the opening of the passage,
an elastic membrane disposed in said pump chamber covering said gas
inlet means and said vent passage including said flexible
diaphragm, and a thermally insulated chamber for retaining cooling
and gas generating means therein, whereby said perfusion medium is
adapted to be circulated through said living organ by the pressure
of said respiratory gas contained in said pump chamber.
8. The apparatus according to claim 7, wherein said thermally
insulated chamber is adapted to contain solid CO.sub.2 and said gas
generating means is solid CO.sub.2.
Description
The invention concerns a procedure for preservation of living
organs by using a cooled perfusion enriched with a respiratory gas
as well as an apparatus for the execution of this procedure.
The existing apparatus for perfusion and for the conservation of
organs are mainly used for stationary operating due to their size
and large weight and because electric energy is needed for running
them. Another disadvantage is the fact that the rate of flow of the
perfusion pump is manual and fixed by the circumstance that the
living organ is endangered, if the pressure of solution in the
vessel rises.
The main problem is that the organs have to be transported, because
the donor and the receptor of a living organ, e.g. a human kidney,
are usually in different places. Therefore it is often not possible
to use the offered organ because without preservation an organ
remains vital only for a very short time and transport in existing
devices is not possible due to the aforementioned reasons.
The present invention solves this problem and removes the
disadvantages of the existing devices. The invention makes it
possible to produce a portable, apparatus for perfusion,
independent from electricity and with pumping characteristics that
save the organ, with all the necessary provisions for
regulation.
This invention is characterized by automatic regulation of the
perfusion which is adapted to the flow resistance in the organ,
using a perfusing pump, which is driven by a gas, e.g., by a
respiratory gas.
The operation of the perfusion pump and the cooling of the
perfusate are achieved by CO.sub.2 -gas resulting from dry ice. The
dry ice can even be used to run a pumping device to oxygenate the
perfusate. The cooling temperature of the perfusate is kept
constant by changing the position or the insulation of the dry ice
compartment in relation to the organ and pump compartment.
The operation of the perfusion pump may be changed from the
CO.sub.2 -gas to a respiratory gas. In this case, the respiratory
gas after passing the pump is used to oxygenate the perfusate. The
apparatus for the execution of this procedure is characterised by a
thermally insulated receptacle which contains one compartment for
the pump, one for the organ and, if necessary, one for the dry ice.
The pump compartment is provided with an inflow and an outflow
valve for the perfusate the gas enters through a gas inlet and is
vented through a pressure or volume monitored outlet valve.
Further the device is provided with regulators for monitoring the
physiologic pulse form, the pulse frequency, the rate of flow and
the maximal pressure of perfusion for a pulsating or non pulsating
organ perfusion, as well as for operating under hyperbaric
conditions in the organ compartment.
In the drawings examples for the execution of the invention are
illustrated.
FIG. 1 shows a section through a perfusion apparatus with a
pressure monitored outlet valve for the gas.
FIG. 2 shows a variation of the perfusion apparatus in FIG. 1.
FIG. 3 shows a perfusion apparatus driven by dry ice.
FIG. 4 shows a part of a perfusion apparatus with a magnetic outlet
valve.
The apparatus for perfusion shown in FIG. 1 consists of a
receptacle with thermoinsulation 2. It is divided into a pumping
compartment 3 and an organ compartment 4. In the pump compartment 3
there are the passive inflow valve 5 and the passive outflow valve
6 for the perfusate 21, the gas inlet 7 and the gas outlet 8 as
well as the pressure monitored outlet valve 9 for the Gas. The
latter is composed of a mobile part in the form of a prestressed
monostabile membrane 10 with an opening 11 for the gas and a fixed
part 12, the valve fitting. A monostabile membrane is a membrane,
which after deflecting to one side returns automatically into the
original position.
The gas inlet 7 is directed through a tube 13 which carries the
fixed part 12 of the outlet valve 9 for the gas. This tube 13 is
inserted with an outer thread 13a into an inner thread on the
receptacle 1. By turning the tube 13 the position of the part 12
and at the same time the stressing of the membrane 10 can be
changed. Above the gas outlet 8 a surplus-pressure valve 14 is
mounted.
The organ compartment 4 includes the organ 15, which is to be
conserved. This organ is connected with its artery 16 to a linking
tube 17 for the perfusate. The vein 18 is open to the organ
compartment 4. A section of the linking tube 17 is elastically
widened (19). The organ 15 enclosed in the organ compartment 4 is
subjected to the pressure of an air cushion 20. The liquid for
perfusion, shortened to "the perfusate" 21, has a different level
in the pumping compartment 3 to that in the organ compartment 4. A
filter 22 is installed in the perfusion circuit.
The apparatus for perfusion functions in the following way: From a
pressure flask, not shown in the drawings, a respiratory gas enters
the tube 13 through the gasinlet 7 and continues from there to the
pump compartment 3, where it bubbles through the perfusate 21,
which is thereby enriched with the gas. The gas is collected above
the perfusate and, of the outlet valve 9 for the gas is closed,
builds up a pressure in the pump compartment 3. This pressure pumps
the perfusate through the passive outflow valve 6 via the linking
tube 17 into the artery 16 of the organ 15. The organ is perfused
in direction of the arrows. The perfusate flows out of the vein 18
into the organ compartment 4, where it collects at the bottom. By
increasing the volume of the perfusate in the organ compartment the
overlying air cushion 20 becomes compressed. By achieving the
desired pressure in the pump compartment 3 the prestressed membrane
10 is suddenly lifted from the fixed part 12 of the outletvalve 9
and takes position 10a. The gas is vented through the opening 11
and the gasoutlet 8. The pressure in the pump compartment 3
decreases. The previously compressed air cushion 20 in the organ
compartment 4 pushes the perfusate through the inflow valve 5 back
into the pump compartment 3. By running through the filter 22 the
perfusate is cleaned. As soon as the pressure in the organ
compartment 4 and in the pump compartment 3 falls to the original
level, the membrane 10 returns to the starting position 10 and
closes the outlet valve 9 for the gas. The gas is still running
through the gas inlet 7 and a new pumping rate starts. By turning
the tube 13 the stressing of the membrane 10 can be changed. If the
fixed part 12 on the outlet valve 9 is lifted, the valve 9 already
opens at a lower pressure. By this means the maximal pulse pressure
can be lowered, the rate of flow reduced and the pulse frequency
raised. The pulse form and the volume of perfusion per time unit
are monitored according to these conditions. They can also be
altered in a similar manner by regulating the gas in flow. If the
flow resistance in the organ 15 rises, then, at a constant gas in
flow, the desired pressure in the pump compartment 3 is reached
sooner and after a smaller rate of flow per pumping stroke. By
means of the pressure monitored membrane 10 the pump regulates
automatically, like a heart, the pulse frequency and the rate of
flow adapted to the flow resistance in the organ 15. The maximal
pulse pressure per pumping stroke is unchanged. This safely avoids
the dangerous destruction of the organ 15 caused by over-pressure
during perfusion. As a further advantage the best corresponding
volume of flow in relation to the organ resistance is maintained.
The elastic sections 19 in the wall of the linking tube 17 for the
perfusate, mounted after the outflow valve 6, absorb the pulse
strokes and, if the elasticity is very high, a pulseless,
continuous perfusion of the organ can be achieved, despite the
pulsations from the pump.
A surplus-pressure valve 14 is provided at the gasoutlet 8 to
obtain a hyperbaric perfusion. In contrast to FIG. 1 referring now
to the perfusion apparatus shown in FIG. 2, the gas, after entering
through the tube 13, is separated from the perfusate 21 by an
elastic membrane 23. The gas collects between membrane 10 and the
elastic membrane 23 until the pressure opens the gas-outlet valve
9. The gas is vented through the gas outlet 8a and bubbles through
the perfusate into the organ compartment 4. The counterpressure is
effected by the contracting elastic membrane 23. The gas pressure
pushes the perfusate from the pump compartment 3 through the filter
22, via outflow-valve 6a and the elastic enlargement 19 of the
linking tube 17 into the artery 16 of the Organ 15. After perfusing
the Organ in direction of the arrows the perfusate flows out of the
vein 18 into the organ compartment 4 and from there via
inflow-valve 5a in the pump compartment 3.
At the membrane 10 an additional inlet-valve 24 for the gas is
mounted, which at the end of a pumping stroke is lifted together
with the opening membrane 10 and closes the gasinlet on the tube
13. By this means the gas-supply is interrupted until the next
pumping stroke and the driving gas can be economized.
The perfusion-apparatus shown in FIG. 3, contrary to the other two
models can be driven with CO.sub.2 -gas resulting from dry ice 32
or with a respiratory gas from a pressure flask. Besides the pump
compartment 3 and the organ compartment 4 there is an additional
pressure compartment 31 for the dry ice 32. This
dry-ice-compartment 31 is thermally insulated against the organ
compartment 4 by the insulation 33. A tube 34 is connected to the
compartment 31 at the joint 13 on the gas inlet 7. The gas entering
through the tube 13 is separated from the perfusate 21 by an
elastic membrane 23 as in FIG. 2. For the oxygenation of the
perfusate with air an air-outlet valve 36 and an air-inlet-tube 37
are provided. They open the organ compartment 4 to the open air
outside. For operation with respiratory gas from a pressure flask,
e.g., if they lack dry ice in a hospital, the connections
illustrated by dashed lines are necessary: A connecting tube 38
between air-inlet-tube 37 and gas-outlet 8 as well as a connection
39 to a pressure flask not shown in the drawings. A
surplus-pressure valve 35 in the linking tube 34 may be mounted for
safety. The apparatus for perfusion in FIG. 3 functions in the
following way: The CO.sub.2 -gas resulting from the dry ice 32 in
compartment 31 by warming up, runs through the linking tube 34 into
the gasinlet 7 of the perfusion pump and causes a pressure on the
elastic membrane 23, if the gas-inlet valve 9 is closed. The
perfusate 21 is thereby transported from the pump compartment 3
through the outflow-valve 6 into the artery 16 of the organ 15. The
perfusate flowing out of the vein 18 raises the level of the
perfusate in the organ compartment 4 and presses the air in the
upper part of the compartment 4 out through the air-outlet valve
36. The prestressed membrane 10 is suddenly lifted from the valve
fitting 12, if the desired pressure is achieved in the pump
compartment 3. The CO.sub.2 -gas is vented through the opening 11
and the gas-outlet 8. The elastic membrane 23, liberated from the
gas pressure, contracts and the perfusate 21 flows from the organ
compartment 4, via inflow-valve 5 and filter 22 in the pump
compartment 3. The level of the perfusate in the organ compartment
4 falls back to the position illustrated by dashed lines. A low
pressure is built up in the upper part of the organ compartment 4
if the air-outlet valve 36 is closed. The air from outside is
sucked in through the air-inlet-tube 37, bubbles through the
perfusate 21 and oxygenates it. If the pressure in the pump
compartment 3 is lowered to the original value, the membrane 10
returns to the starting position and closes the gas-outlet valve 9.
The driving gas continues to run through the gas inlet 7 and a new
pumping rate starts. In this way the perfusion apparatus works
completely automatically as long as there remains any dry ice in
compartment 31.
If necessary the perfusion apparatus may be run with a respiratory
gas from a pressure flask. In this case the linking tube 34 is
moved from the joint connection 13 and replaced by the connexion
39, which leads to the flask containing the respiratory gas. The
gas-outlet 8 on the pump compartment 3 is joined to the
air-inlet-tube 37 via connecting-tube 38, which conducts the vented
respiratory gas into the organ-compartment 4, where it bubbles
through the perfusate 21 and oxygenates it. The air is vented
through the air-outlet valve 36. The necessary cooling in this
arrangement is effected with normal ice in compartment 31, i.e., if
using a respiratory gas for operation. The perfusing pump works
just the same way as when operating with dry ice. The desired
constant cooling temperature of the perfusate 21 is effected by a
corresponding position and insulation of the dry-ice-compartment 31
in relation to the compartment for the organ 4 and the pump 3. The
thickness of the insulation 33 is correspondingly selected.
FIG. 4 shows a variation of the pressure monitored outlet-valve 9
for the gas with a magnetic control. This consists of a fixed
cylindrical tube 25 with a lateral gas outlet 26 and of a mobile,
inserted bolt 27 on which a holding plate of metal 28 is mounted at
the upper end. With help of this plate 28 the bolt 27 is held down
by a magnet 29, the magnet being mounted at the upper end of the
tube 25 and in this way closing the gas-outlet 26. When the desired
pressure in the pump-compartment 3 is reached, Then the bolt 27
with holding-plate 28 is suddenly separated from the magnet 29. The
bolt 27 is lifted and the gas is vented through the gas-outlet 26.
The magnet 29 pulls the bolt 27 downwards and closes the
gas-outlet-valve 9 suddenly, if the pressure in the
pump-compartment 3 falls to the starting level. The gas supply is
achieved through a separated gas-inlet 7.
The simple procedure, as well as the low weight and the smal price
of the apparatus and the dry-ice, which supplies the energy for
cooling, perfusion and oxygenation, the few necessary components
for construction together with the completely automatic and safe
operating of the apparatus allow a serial-production of a compact,
portable safely operating and cheap, disposable perfusion-apparatus
in which living human and animal organs can be transported
anywhere.
* * * * *