U.S. patent number 3,892,628 [Application Number 05/316,612] was granted by the patent office on 1975-07-01 for preservation of organs.
This patent grant is currently assigned to Baxter Laboratories, Inc.. Invention is credited to Kay L. Knudson, Gale H. Thorne, Orin Lew Wood.
United States Patent |
3,892,628 |
Thorne , et al. |
July 1, 1975 |
Preservation of organs
Abstract
Apparatus and method of preserving life organs, the apparatus
having an organ container in which the organ may be subjected to
elevated pressure, a pump pulsatilely delivering perfusate into the
organ and an oxygenator to oxygenate the perfusate effluent from
the organ. A constant pressure bias maintains a minimum pressure on
the perfusate between pulses. A fluid flow control system delivers
driving fluid in a pulsed manner to the pump at a selected rate and
at selected pulse duration. The method includes delivering pulsed
oxygenated perfusate to the organ and uniformly conducting
perfusate away from the organ and providing a constant pressure
bias on the perfusate. Loss or gain of liquid volume caused by
waste secretion by the organ is compensated for.
Inventors: |
Thorne; Gale H. (Bountiful,
UT), Wood; Orin Lew (Salt Lake City, UT), Knudson; Kay
L. (Murray, UT) |
Assignee: |
Baxter Laboratories, Inc.
(Morton Grove, IL)
|
Family
ID: |
26980507 |
Appl.
No.: |
05/316,612 |
Filed: |
December 19, 1972 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
|
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863869 |
Oct 6, 1969 |
3738914 |
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Current U.S.
Class: |
435/1.2 |
Current CPC
Class: |
A61M
1/32 (20130101) |
Current International
Class: |
A61M
1/32 (20060101); C12k 009/00 () |
Field of
Search: |
;195/1.7,127
;23/258.5 |
References Cited
[Referenced By]
U.S. Patent Documents
Other References
Eiseman et al., Surgery, Vol. 60, pages 1183-1186, Dec.
1966..
|
Primary Examiner: Huff; Richard L.
Attorney, Agent or Firm: Ellis; Garrettson
Parent Case Text
This application is a division of application Ser. No. 863,869,
filed Oct. 6, 1969, now U.S. Pat. No. 3,738,914.
Claims
What is claimed and desired to be secured by United States Letters
Patent is:
1. In a method of artificially perfusing a life organ which method
includes delivery of perfusate to the organ the improvement of:
developing a pulsatile pressure in the perfusate delivered to the
organ and imposing a minimum pressure bias on the delivered
perfusate circulated through the organ between pressure pulses.
2. A method of articially preserving life organs, comprising the
steps of:
placing the organ into a container;
pulsatilely pumping perfusate into the organ, while maintaining a
minimum pressure bias on the perfusate between pulses and
conducting the perfusate uniformly from the organ;
oxygenating the perfusate drawn from the organ with an oxygenator;
and
controlling the temperature and the pulse rate of the perfusate
conducted to the organ.
3. In a method as defined in claim 2, wherein said placing step
comprises subjecting the organ to elevated pressures within the
container.
4. In a method as defined in claim 2 wherein said oxygenating step
comprises disposing the container at a greater elevation than the
oxygenator and delivering the perfusate from the organ to the
oxygenator by force of gravity.
5. In a method as defined in claim 2 further comprising conducting
organ secretions away from the organ out of the container.
6. In a method as defined in claim 5 further comprising
compensating for the volume of secretions conducted away from the
organ by increasing the volume of perfusate available to the organ.
Description
BACKGROUND
Field of the Invention
The present invention relates to treatment of organs and more
particularly to the clinical and laboratory preservation and
perfusion of life organs.
BRIEF SUMMARY OF THE INVENTION
The present invention is directed to an improved method of
artificially perfusing a life organ and includes the delivery of
perfusate to the organ with pulsatile pressure while imposing a
minimum pressure bias on the delivered perfusate between pressure
pulses. This increases perfusate circulation through the organ
between pulses as well as during the pulses.
BRIEF DESCRIPTION OF THE FIGURES
FIG. 1 is a schematic representation of one presently preferred
system according to the present invention;
FIGS. 2 and 3 are schematic circuit diagrams, each illustrating a
presently preferred control unit which may respectively comprise
part of the system of FIG. 1; and
FIG. 4 is a schematic circuit diagram of another presently
preferred control unit which may also be used in the system of FIG.
1.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
FIG. 1
Referring now to FIG. 1, the organ preservation system, generally
designated 20, is powered by a pneumatic source 22 which is
preferably compressed oxygen. If desired, conventional laboratory
supplied pneumatic source capable of generating pressures on the
order of about 20 to 25 p.s.i. could be used. The compressed oxygen
is communicated through line 24 to a control unit generally
designated 26. The control unit 26 has a plurality of dials 28, 34
and 36 and gauges 30 and 31 which accommodate selective adjustment
and monitoring of the compressed oxygen communicated through the
line 24. Also, the control unit 26 pulses the input oxygen and
communicates the pulsed oxygen to the output 32 of the unit 26.
Significantly, dials 34 and 36 may be used to control the pulse
rate and period of systole, respectively, of the output of the
control unit. An on-off switch 27 and gauge switches 134 and 138
are also provided. A more detailed discussion of the structure and
operation of the control unit 26 will be subsequently more fully
described in connection with FIG. 2.
The pulsed output pressure, termed systolic pressure, from the
control unit 26 is communicated through line 38 to a pump 40. One
suitable embodiment of the pump 40 includes a cylindrical flexible
pump bladder (not shown) fitted with silicone rubber tricuspid type
check valves (not shown) in both ends to insure flow only in the
desired direction. The rigid pump housing 46 encloses the bladder
and seals the bladder at both ends, the pulsating pneumatic
pressures from the control unit 26 being communicated between the
pump bladder and the interior of the pump housing 46.
Perfusate, such as whole blood, disposed within the bladder of the
pump 40, is communicated through the conduit 42 to the simulated
aorta 44 with each high pressure pulse through the line 38. The
simulated aorta 44 is a perfusate or blood-receiving chamber and
has a tubular silicone bladder (not shown) enclosed in a rigid
cylindrical housing 48. The interior of the cylindrical housing 48
is in communication with a constant biasing pressure through line
50 which is, in turn, coupled with the control unit 26. The
pressure in line 50 has a pre-selected magnitude which exerts a
biasing force upon the blood in the aorta 44. The bias pressure is
preferably selectively adjustable in a range of about 0 to 200
millimeters of mercury above ambient. Thus, the forward bias
pressure on the blood will serve as a minimum or diastolic
pressure.
The blood forced through the aorta 44 by the pump 40 is
communicated through line 52 to a temperature bath 54. Although any
suitable temperature bath could be used, one suitable type includes
a coil of line 52 disposed within a constant temperature water
bath.
Blood emitted from the temperature bath 54 is then communicated
through a port 56 to the interior of an organ container 58. Organ
container 58 is preferably formed of transparent material such as,
for example, acrylic plastic so that the organ (not shown) therein
may be readily visually observed without disrupting the
environment. The container 58 is constructed so as to accommodate
elevated internal pressures such as on the order of about three
atmospheres (45 p.s.i.g.). Also, the interior of the container 58
is preferably regulated in temperature with conventional heat
exchange apparatus 238 (FIG. 4). Thus, the container 58 secures an
organ (not shown) in a selected temperature and pressure
environment.
Preferably, a tube 60 is connected to the organ (not shown) so as
to receive excreted waste or by-products of the organ perfusion,
such as urine or bile (when the organ is respectively kidney or
liver). The secretions are conducted to an accumulator 62 where
they are made available for examination and/or laboratory testing.
The secretions may or may not be returned to the system as
perfusate depending upon the preservation requirements of the
particular organ.
After the pulsed blood has been circulated through the organ, the
blood is then carried away from the organ through line 64 to an
oxygenator 66. The oxygenator 66 may be of any suitable
conventional type, for example, a membrane oxygenator. Fresh oxygen
is communicated to the oxygenator 66 through line 68 from the
control unit 26. In the oxygenator 66, carbon dioxide in the blood
is exchanged for oxygen, carbon dioxide rich fluid being
communicated away from the oxygenator 66 through line 70 to the
control unit 26.
The oxygenated blood effluent from the oxygenator 66 is conducted
by line 72 to simulated atrium 74. Significantly, an additional
supply of blood or other perfusate is also in communication with
the atrium 74 through line 76. The supply is maintained in a
reservoir 78 to compensate for any reduction in blood volume in the
system resulting from secretion of fluids through the line 60 to
the accumulator 62. Also, it should be appreciated that the
container 58 is disposed at a greater vertical height than the
oxygenator 66 and the oxygenator 66 is, in turn, disposed at a
greater height than the atrium 74. Thus, the flow of blood from the
organ in the container 58 through the oxygenator 66 and to the
atrium 74 is gravity flow.
Atrium 74 is a flexible silicone rubber receiver or chamber for
receiving the blood or other perfusate from the oxygenator 66 and
the reservoir 78. Atrium 74 carries a substantial supply of blood
and, therefore, ensures a non-interrupted venous inflow of blood to
the pump 40 and also provides a relatively uniform pressure head
for passive filling of the pump 40. Thus, the atrium 74 cooperates
with the pump 40 to closely simulate natural physiologic
conditions.
Briefly summarizing the method of preserving an organ in the
container 58, the system is primed with perfusate such as whole
blood and purged of all air or gas in the blood circulatory system.
Pneumatic pressure, such as compressed oxygen, is pulsed by the
control unit 26 which, in turn, actuates the pump 40 forcing blood
into the aorta 44 and, thereafter, through the temperature control
bath 54 into the organ (not shown). A bias pressure on the aorta 44
regulated through the control unit 26 ensures a minimum diastolic
pressure in the system.
Any liquid waste or like product created by the organ in the
container 58 during perfusion and preservation is delivered by the
organ secretion ducts to the tube 60 which conducts the secretion
to the accumulator 62. The secretion is then readily available for
examination and/or laboratory testing or it may be returned to the
system as perfusate. A perfusate reservoir 78 regulates and
maintains a fixed volume of blood within the system and thus
compensates any fluid removed through the tube 60 as a
secretion.
A pressure head is developed at the oxygenator 66 and the atrium 74
by locating the organ container 58 at a greater vertical height
than the oxygenator 66, oxygenator 66 being in turn at a greater
vertical height than atrium 74. The developed pressure head is
sufficient to drive the blood through the oxygenator 66. Also, the
control system 26 is manually set to regulate and control the rate
of oxygenation as required by the organ.
The oxygenated blood entering the atrium 74 is made available to
the pump 40 in a continuous uninterrupted manner so that the pump
40 may be efficiently filled with blood when the pneumatic line 38
is vented to ambient pressure, as between succesive systolic
pressure pulses. When the pneumatic line 38 is vented to ambient
pressure, the pressure head in the atrium 74 opens the upper pump
valve (not shown) and allows the pump to be refilled preparatory to
initiation of another cycle of pumping.
The Control Unit Embodiment of FIG. 2
Referring to FIG. 2, the control unit 26 comprises a pressure
source 22 which, as above described, may be compressed oxygen. It
is presently preferred that the pressure from source 22 enter the
control unit 26 at about 20 p.s.i.g. (pounds per square inch
gauge). The pressure from the source 22 is communicated through
line 90 to an oscillator circuit 92. Oscillator circuit 92 has an
or/nor gate 94 one side of which is in communication with lines 90.
The other side of the or/nor gate 94 is in communication through
line 96 with a pneumatic capacitor 98. A needle valve 100 controls
the flow of fluid from the capacitor 98 to a fixed resistor 102 and
also to or/nor gate 104.
The regulated pressure supplied to the gate 94 passes freely
through the gate until sufficient control pressure builds up in the
capacitor 98 to switch the gate 94 off. When the gate 94 is off,
the capacitor 98 discharges through the needle valve 100 and vents
through the restrictor 102. When the pressure in pneumatic
capacitor 98 reaches a predetermined minimum level, the gate 94
switches on again to conduct the 20 p.s.i.g. pressure through line
96 to again allow the pressure to build up in the capacitor 98.
During the period when the gate is off the 20 p.s.i.g. pressure is
conducted through line 106 to the gate 104. Thus, 20 p.s.i.g.
pressure is alternately conducted to the gate 104 and vented
through the resistor 102. The rate of alternation is termed the
"pulse rate" and the pulse rate is determined by the setting on the
needle valve 100, needle valve 100 controlling the rate of charge
and discharge of the capacitor 98. The needle valve 100 may be
manually set by turning knob 34 (FIG. 1).
A pressure regulator 108 reduces the 20 p.s.i.g. input pressure to
10 p.s.i.g. and thereafter conducts the reduced pressure through
line 110 to the gate 104. A high pressure pulse in the line 106
switches the gate 104 to the on position so that the 10 p.s.i.g.
pressure through line 110 is conducted through line 112 as a pulse
to the switching valve or fluid valve 116.
Fluid valve 116 responds to the pressure pulse from gate 104 by
opening communication between line 118 and the output 32 of the
control unit 26 (see also FIG. 1). Line 118 communicates pressure
from the source 22, a regulator 120 being interposed into the line
to accommodate selective regulation of the pressure to the pump 40
(FIG. 1).
When gate 104 is switched off, i.e., when the oscillator 92 vents
through the fixed resistor 102, the fluid valve 116 will be
operated to vent the increased pressure developed in the pump 40.
Fluid valve 116 is biased toward the vent position by fluid
pressure existing in line 122. A pressure regulator 124 is disposed
in the line 122 and controls the amount of pressure delivered to
the right side of the fluid valve 116. Thus, the setting on
regulator 120 determines the pressure which is necessary to move
the valve 116 from the extreme left position to the extreme right
position to communicate driving fluid pressure to the output 32.
The time period during which driving fluid is communicated through
the output 32 is increased by increasing the pressure setting on
the regulator 124. Hence, regulator 124 determines the period or
duration of the systolic pressure.
A pneumatic capacitor 126 is interposed between the regulator 124
and the pressure source 22 to dampen minor fluctuations in the
pressure line caused by the oscillator circuit 92.
Fluid pressure from the source 22 is communicated through line 128
to the aorta 44 (FIG. 1) as above described. A regulator 130
controlled by knob 28 (FIG. 1) is disposed in the line 128 and is
adjustable to set the bias fluid pressure in line 128 to a
predetermined minimum diastolic pressure.
Pressure gauge 30 is coupled to a switch 134 (see also FIG. 1)
disposed in line 136. When switch 134 is in one position, the
driving pressure to the pump 40 is registered on the gauge 30. When
the switch is placed in the other position, the bias pressure to
the aorta 44 is indicated on the gauge 30. The other gauge 31 is
coupled to a switch 138 which is disposed in line 140. In one
position the switch 138 causes the gauge 31 to register the supply
pressure from the pressure source 22 and, in the opposite position,
causes gauge 31 to register the pressure on the right side of fluid
valve 116.
The Embodiment of FIG. 3
The control unit embodiment generally designated 144 and best
illustrated in FIG. 3 is, in many respects, substantially identical
to the control unit 26, like parts having like numerals throughout.
The control unit 144 has a fluid valve control subsystem generally
designated 149 and including a fluid valve 146 which is biased by
spring 148 toward the vent position. Thus, in the absence of a high
pressure systolic pulse at the left-hand side of the fluid valve
146, the pump 40 (FIG. 1) will be vented through the valve 146. The
spring bias eliminates the requirement for a regulated fluid
pressure source to switch the fluid valve to vent (i.e., to
terminate the systole output).
The period of systole output is controlled by the or/nor gates 150
and 152 and the needle valve 154 as will now be described. The
pulse signals of the oscillator 92 switch the gate 150 to the on
condition, causing fluid in line 156 to be conducted through the
gate 150 and through restrictor 158 to the input 160 of gate 152.
It should be observed that the fluid in line 156 is communicated
from a pneumatic capacitor 162 which is, in turn, connected to
input line 164. Capacitor 162 provides a more constant pressure to
the oscillator circuit 92. Input line 164 is in communication with
the fluid supply 22 when switch 166 is in the illustrated on
position. Switch 166 permits regulation of the supply pressure
prior to placing the control unit 144 in the on condition. The
pressure regulation is accommodated by regulator 168. Fluid from
the pressure source is initially filtered through filter 170 and,
when switch 166 is in the illustrated closed position, the
regulated fluid pressure is conducted through line 164 to the
capacitor 162 and made available to the gate 150.
When gate 150 is in the on condition, as above described, a
pressure pulse will appear at gate 152 switching gate 152 to the on
condition. Thus, the gate 150 isolates the systole control
subsystem 149 from the oscillator circuit 92.
When gate 152 is in the on condition, the fluid in line 156 is
communicated through line 172 to the left-hand side of fluid valve
146 causing the valve to communicate the fluid pressure in line 118
to the pump at output 32 (see FIG. 1). Significantly, the amount of
pressure required to place gate 152 in the on condition is governed
by the needle valve 154. Thus, the needle valve 154 is adjusted to
regulate the period of systolic output of the fluid valve 146. When
gate 152 is again switched to the off condition, the spring 148
will return the fluid valve 146 to the vent position, fluid in the
left-hand side of the valve 146 being vented through restrictor
174.
It should be appreciated in the control unit 144 that the gauge 31
and the switch 138 are connected so that in one position gauge 31
monitors the pressure as regulated prior to placing the switch 166
in the on condition and, in the opposite position, monitors the
pressure as supplied to the oscillator circuit. The control unit
144 has the advantage of more positive control of the switching
action of the fluid valve 146.
The Control Unit Embodiment of FIG. 4
The control unit illustrated in FIG. 4 and generally designated 180
is similar to the control units 26 and 144 above described, like
parts having like numerals throughout. The control unit 180 differs
in that it provides a parallel circuit operating and controlling
two fluidic pumps simultaneously Also, the unit 180 is constructed
for operation under hyperbaric conditions.
Most of the components of the control unit 180 are carried within a
hyperbaric chamber 182 which may be formed of acryllic plastic and
which is constructed so as to maintain a hyperbaric environment.
The chamber 182 also contains the organ container 56 (not shown in
FIG. 4).
The unit 180 comprises an oscillator circuit 184 which is
substantially similar to the oscillator circuit 92 above described,
circuit 184 comprising a gate 94, a fluidic capacitor 98 and a
needle valve 100. The control unit 180 differs from control unit 92
in that a restrictor 186 is disposed between the line 106 and
restrictor 102. Restrictor 186 minimizes the volume of pneumatic
fluid required by the unit 180 and allows the size of the capacitor
98 to be minimized. The operation of oscillator 184 is essentially
identical to the operation of oscillator 92 above described.
The output of oscillator 184 in line 106 is simultaneously
communicated to each of two fluid valve control subsystems 149
which may be substantially identical to the fluid valve control
subsystem 149 above described and illustrated in FIG. 3. The
subsystems 149 are connected in parallel and relate one with
another with line 192 which equalizes the fluid pressure between
gates 150 and also with line 194 which communicates fluid in line
156 to gates 152 simultaneously. Each of the fluid valves 146 is
connected to a separate pump 196 and 198.
With continued reference to FIG. 4, fluid from the source 22 is
communicated through the filter 170 to the regulator 168 as above
described (FIG. 3). The system is operated when the switch 166 is
moved from the off positioin illustrated in FIG. 4 to the on
position opposite the position illustrated in FIG. 4. In the on
position the oscillator 184 is energized and a pulsatile signal is
developed by the subcircuits 149 to drive the pumps 196 and 198.
The input pressure through the regulator 168 is also communicated
through line 200 to switch 202 so that gauge 204 measures the
pressure communicated through line 206 to the oxygenator 66. A
restrictor 208 dampens pressure fluctuation in the line servicing
the pressure gauge 204 protecting it from shock damage.
The pressure from the supply 22 is also conducted to regulators 210
and 212 which control the pumping pressure to pumps 198 and 196
respectively. A switch 214 is provided to selectively turn the pump
198 on or off so that a single pump may be operated if desired.
Also, switch 216, in one position, allows the pressure available to
pump 196 to be registered on the gauge 218 and, in the opposite
position, allows the pressure in pump 198 to be monitored on gauge
218.
Gauge 218 is connected to switch 220 which in the illustrated
position monitors the pressure on the selected one of the pumps 198
or 196 and, in the opposite position, monitors the pressure to the
aorta. A regulator 222 controls the pressure supplied to the
oxygenator 66 and a flow meter 224 monitors and controls the rate
of flow to the oxygenator. Diodes 226 and 228 prevent application
of negative pressure on the gauge 218 to avoid damaging the
gauge.
A regulator 230 sets and controls the pressure in the hyperbaric
chamber 182 and relief valve 232 functions as a safety valve to
avoid overpressurizing the chamber 182. The pressure in the chamber
182 is monitored by a gauge 234 which is protected from pressure
fluctuation by a restrictor 236.
If desired, as illustrated in FIG. 4, the hyperbaric chamber 182
may be provided with a heat exchanger 238 to maintain a constant
predetermined temperature within the chamber 182 and/or of the
perfusate.
The operation of the control circuit 180 is substantially similar
to the operation of the control circuit 144 (FIG. 3) above.
However, the unit 180 simultaneously drives two pumps which may be
connected to the same or different organs. The system accommodates
preservation of an organ in a manner closely approaching actual
physiological conditions and accommodates a wide variety of
controls to achieve maximum preservation effect.
The invention may be embodied in other specific forms without
departing from the spirit or essential characteristics thereof. The
present embodiments are, therefore, to be considered in all
respects as illustrative and not restrictive, the scope of the
invention being indicated by the appended claims rather than by the
foregoing description, and all changes which come within the
meaning and range of equivalency of the claims are therefore to be
embraced therein.
* * * * *