U.S. patent application number 11/944377 was filed with the patent office on 2008-03-20 for method for preserving organs for transplantation.
Invention is credited to Jackson Streeter.
Application Number | 20080070229 11/944377 |
Document ID | / |
Family ID | 26995155 |
Filed Date | 2008-03-20 |
United States Patent
Application |
20080070229 |
Kind Code |
A1 |
Streeter; Jackson |
March 20, 2008 |
METHOD FOR PRESERVING ORGANS FOR TRANSPLANTATION
Abstract
Methods and apparatus for preserving tissue such as harvested
organs for transplant are described. A preferred method includes
delivering to a harvested organ an effective amount of
electromagnetic energy, the electromagnetic energy having a
wavelength in the visible to near-infrared wavelength range,
wherein delivering the effective amount of electromagnetic energy
includes selecting a predetermined power density (mW/cm.sup.2) of
electromagnetic energy to deliver to the organ while in hypothermic
or normothermic storage. A preferred apparatus includes a container
having a cooling chamber to receive the harvested organ and at
least one light source mounted on the container to illuminate the
interior cooling chamber, said light source emiting light which
produces a biostimulative effect on tissue placed in the cooling
chamber thereby preventing or retarding damage to the tissue during
storage or transport.
Inventors: |
Streeter; Jackson; (Reno,
NV) |
Correspondence
Address: |
KNOBBE MARTENS OLSON & BEAR LLP
2040 MAIN STREET
FOURTEENTH FLOOR
IRVINE
CA
92614
US
|
Family ID: |
26995155 |
Appl. No.: |
11/944377 |
Filed: |
November 21, 2007 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10338949 |
Jan 8, 2003 |
7316922 |
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11944377 |
Nov 21, 2007 |
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60347171 |
Jan 9, 2002 |
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60353639 |
Jan 31, 2002 |
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Current U.S.
Class: |
435/1.1 |
Current CPC
Class: |
A61N 5/0613 20130101;
F25D 3/08 20130101; A01N 1/02 20130101; A01N 1/0294 20130101; F25B
21/02 20130101; F25D 2331/8014 20130101; A61P 43/00 20180101; F25D
2331/804 20130101 |
Class at
Publication: |
435/001.1 |
International
Class: |
A01N 1/00 20060101
A01N001/00; A61P 43/00 20060101 A61P043/00 |
Claims
1. A method of preserving a harvested organ for transplant, the
method comprising delivering an effective amount of electromagnetic
energy to the harvested organ, the electromagnetic energy having a
wavelength in the visible to near-infrared wavelength range,
wherein delivering the effective amount of electromagnetic energy
comprises selecting a predetermined power density of
electromagnetic energy to deliver to the organ.
2. The method of claim 1, wherein the predetermined power density
is selected to be at least about 1 mW/cm.sup.2.
3. The method of claim 1, wherein the predetermined power density
is selected to be in a range from about 0.01 mW/cm.sup.2 to about
100 mW/cm.sup.2.
4. The method of claim 3, wherein the predetermined power density
is selected to be in a range from about 2 mW/cm.sup.2 to about 20
mW/cm.sup.2.
5. The method of claim 1, wherein the electromagnetic energy has a
wavelength in a range from about 630 nm to about 904 nm.
6. The method of claim 1, wherein the electromagnetic energy has a
wavelength of about 830 nm.
7. The method of claim 1, wherein the electromagnetic energy is
pulsed.
8. The method of claim 1, further comprising placing the harvested
organ in a hypothermic environment to arrest function of the organ
and wherein delivering the electromagnetic energy comprises
delivering the electromagnetic energy to the harvested organ in the
hypothermic environment.
9. The method of claim 8, wherein placing the harvested organ in a
hypothermic environment comprises placing the harvested organ in a
portable hypothermic container.
10. The method of claim 1, further comprising: placing the
harvested organ in a normothermic environment; perfusing the
harvested organ with a perfusate; and delivering the
electromagnetic energy to the harvested organ in the normothermic
environment.
11. A method of preserving an organ or tissue for transplantation,
the method comprising: providing the organ or tissue; and
irradiating the organ or tissue with electromagnetic radiation
having a power density in a range between about 0.01 mW/cm.sup.2
and about 100 mW/cm.sup.2.
12. The method of claim 11, wherein the organ or tissue is selected
from the group consisting of: heart, lung, kidney, liver, and
pancreas.
13. The method of claim 11, wherein providing the organ or tissue
comprises placing the organ in a transportable container.
14. The method of claim 13, wherein the container comprises one or
more sources of electromagnetic radiation.
15. The method of claim 14, wherein irradiating the organ or tissue
is performed during storage or transport of the container.
16. The method of claim 13, wherein the organ or tissue is
suspended in a preservation medium within the container.
17. The method of claim 11, wherein irradiating the organ or tissue
is performed while the organ or tissue is being stored or
transported.
18. The method of claim 17, wherein irradiating the organ or tissue
is performed continuously during substantially the entire period of
time that the organ or tissue is being stored or transported.
19. The method of claim 11, wherein irradiating the organ or tissue
is performed after explantation of the organ or tissue from a donor
and before implantation of the organ or tissue into a
recipient.
20. The method of claim 11, wherein irradiating the organ or tissue
is performed while the organ or tissue is at a temperature below
the normal body temperature of the organ or tissue.
21. The method of claim 11, wherein irradiating the organ or tissue
is performed while the organ or tissue is in a normothermic
environment and is perfused with a perfusate.
22. A method of preserving an organ for transplant, the method
comprising: providing the organ explanted from a donor; and
delivering an effective amount of electromagnetic energy to the
organ to extend a time period of safe preservation of the organ
beyond about four hours after the organ was explanted from the
donor.
23. The method of claim 22, wherein the electromagnetic energy has
a wavelength in a range between about 630 nm to about 904 nm and
has a power density in a range between about 0.01 mW/cm.sup.2 and
about 100 mW/cm.sup.2.
24. A method of preserving an organ or tissue for transplantation,
the method comprising: providing the organ or tissue explanted from
a donor; and irradiating the organ or tissue with electromagnetic
radiation while the organ or tissue is being transported from the
donor to a recipient.
25. The method of claim 24, wherein the electromagnetic radiation
has a wavelength in a range between about 630 nm to about 904 nm
and has a power density in a range between about 0.01 mW/cm.sup.2
and about 100 mW/cm.sup.2.
Description
CLAIM OF PRIORITY
[0001] The present application is a divisional application of U.S.
patent application Ser. No. 10/338,949, filed Jan. 8, 2003,
incorporated in its entirety by reference herein, and which claims
priority under 35 U.S.C. .sctn.119(e) to U.S. Provisional
Application Nos. 60/347,171, filed Jan. 9, 2002, and 60/353,639,
filed Jan. 31, 2002, the entireties of which are hereby
incorporated by reference.
FIELD OF THE INVENTION
[0002] The present invention relates to apparatus and methods for
preserving tissue, such as harvested organs for transplant.
BACKGROUND OF THE INVENTION
[0003] Over the past thirty years, solid organ transplantation has
become an increasingly viable treatment option for a variety of
diseases and conditions. For example, in the United States alone,
kidney transplants are now performed at an annual rate of over
9,000, and heart transplants are performed at the rate of over
1,500 per year. However, rejection of the transplanted tissue due
to the recipient's normal immune response and transplant-related
pathophysiology in the graft tissue continues to be a major hurdle
to successful transplantation. In particular, graft tissue quality
is a major factor underlying graft rejection. The method of storing
a donor organ once removed from the donor greatly impacts.
[0004] Typically, once a donor organ is harvested, the organ is
preserved by storage in a portable hypothermic container under
sterile conditions. Thus, methods to preserve donor tissue
integrity have focused primarily on maintenance of properly
hypothermic and sterile conditions. However, tissue integrity
compromised after harvesting and during storage remains a barrier
to improved long-term survival of organ transplants. Even under
carefully monitored hypothermic and sterile conditions, ischemia
and reperfusion injury negatively impact donor tissue quality. In
particular, ischemic damage to the vascular endothelium can result
in accelerated graft atherosclerosis, which adversely affects
ultimate survival of the graft. In addition, compromised donor
tissue contributes to other chronic pathologies in the graft that
result in substantial rates of graft loss.
[0005] The problem of compromised organ tissue integrity is a major
factor contributing to inadequate supplies of organs for
transplant. About one in four patients awaiting cardiac
transplantation dies while waiting for a suitable donated heart,
and similar supply problems plague candidate recipients of other
organs. The waits are due in part to insufficient rates of organ
donation from potential donors, but also due in part to
insufficient progress in developing successful techniques for
preserving donated organs beyond very limited time periods after
harvesting. Recent advances in immunosuppressive therapy that
otherwise after harvesting. Recent advances in immunosuppressive
therapy that otherwise have made organ transplantation more
feasible have merely exacerbated the problems of organ supply.
Thus, a major hurdle in exploiting improved organ transplantation
techniques has been the inability to extend safe preservation of
donated organs beyond the currently accepted time limit of about
four hours. Preservation time limits of a few hours effectively
limit the geographic area within which a donated organ can be
transported and still be successfully transplanted. Such time
limits also make it difficult or impossible to meaningfully
evaluate the donated organ before transplant.
[0006] Known organ preservation approaches typically include
hypothermic arrest and storage in a liquid medium or perfusate,
such as known cardioplegic preservation solutions for hypothermic
preservation of donated hearts. However, such approaches still do
not prevent myocardial damage due to ischemia, reperfusion, fluid
and electrolyte imbalances leading to edema, and metabolic
exhaustion at the cellular level leading to a degradation of
high-energy phosphates, all known to be factors contributing
substantially to tissue damage.
[0007] To avoid the problems associated with hypothermic arrest and
storage, it is known in the art that normothermic preservation
eliminates the need to arrest organ function and the need for
hypothermic storage, and reduces reperfusion injury and other time
dependent tissue injury associated especially with metabolic
rundown and depletion of high-energy phosphates. Thus, known
methods for extending organ preservation involve attempts to
simulate near-normal physiologic conditions, using various
approaches. One approach involves harvesting almost all the donor's
organs and using the system to perfuse the needed organ under
normothermic conditions. However, as an element of routine
transplant practice, this approach is limited because of the myriad
practical difficulties involved in removing and preserving heart,
lungs, liver, pancreas, and kidneys all together and all in
functioning condition. Another related approach to achieving
extended extracorporeal preservation of a donor organ involves
providing continuous sanguineous perfusion, while maintaining the
donor organ in the normal functioning state. Thus, known approaches
include apparatus, methods and physiologic media that create an
extracorporeal circuit for sanguineously perfusing the harvested
organ at normothermic temperatures, thus prolonging preservation of
the harvested organ for up to about twenty-four hours or longer.
However, such approaches remain relatively cumbersome, are
relatively costly, are not readily amenable to transport because
they involve fairly complex perfusion systems, and have met with
limited success.
[0008] In the field of surgery, high-energy laser radiation is now
well accepted as a surgical tool for cutting, cauterizing, and
ablating biological tissue. High-energy lasers are now routinely
used for vaporizing superficial skin lesions and, and to make deep
cuts. For a laser to be suitable for use as a surgical laser, it
must provide light energy at a power sufficient to heat tissue to
temperatures over 50 C. Power outputs for surgical lasers vary from
1-5 W for vaporizing superficial tissue, to about 100 W for deep
cutting.
[0009] In contrast, low level laser therapy involves therapeutic
administration of laser energy to a patient at vastly lower power
outputs than those used in high energy laser applications,
resulting in desirable biostimulatory effects while leaving tissue
undamaged. For example, in rat models of myocardial infarction and
ischemia-reperfusion injury, low energy laser irradiation reduces
infarct size and left ventricular dilation, and enhances
angiogenesis in the myocardium. (Yaakobi et al., J. Appl. Physiol.
90, 2411-19 (2001)). Low level laser therapy has been described for
treating pain, including headache and muscle pain, and
inflammation. The use of low level laser therapy to accelerate bone
remodeling and healing of fractures has also been described. (See,
e.g., J. Tuner and L. Hode, Low LEVEL LASER THERAPY,
Stockholm:Prima Books, 113-16, 1999, which is herein incorporated
by reference).
[0010] However, known low level laser therapy methods are
circumscribed by setting only certain selected parameters within
specified limits. For example, known methods are characterized by
application of laser energy at a set wavelength using a laser
source having a set power output. Specifically, known methods are
generally typified by selecting a wavelength of the power source,
setting the power output of the laser source at very low levels of
5 mW to 100 mW, setting low dosages of at most about 1-10
Joule/cm.sup.2, and setting time periods of application of the
laser energy at twenty seconds to minutes. However, other
parameters can be varied in the use of low level laser therapy. In
particular, known low level laser therapy methods have not
addressed the multiple other factors that may contribute to the
efficacy of low level laser therapy.
[0011] Against this background, a high level of interest remains in
finding new and improved methods for preserving harvested organs
for transplant thus to extend the time period for preservation. A
need thus remains for simple, portable and cost-effective apparatus
and methods that provide the ability to extend the organ
preservation period beyond accepted limits, while avoiding
time-dependent tissue damage due to ischemia and reperfusion, and
depletion of high-energy phosphates. A need also remains for
apparatus and methods that help to overcome organ transplant
rejection, and enhance the survival time of transplanted organs, by
improving the tissue quality of transplanted organs.
SUMMARY OF THE INVENTION
[0012] The light therapy apparatus and methods for preserving
tissue, including organs, for transplant are based in part on the
new and surprising discovery that applying electromagnetic energy
to the tissue during transport, generally following explantation,
appears to prevent or retard tissue damage in a harvested organ,
thus extending the time period of preservation and helping to
overcome transplant rejection by improving tissue quality in
preserved organs. Preferably the electromagnetic energy that is
applied falls within a select wavelength range and at a select
range of power density (i.e., power per unit area)
[0013] In accordance with one embodiment, there is provided an
apparatus for transporting living tissue, such as an organ,
comprising a tissue preserving container having an interior cooling
chamber adapted to receive a tissue, and at least one light source
mounted on the container so as to illuminate the interior cooling
chamber from a multiplicity of directions, where said light source
emits optical radiation which produces a biostimulative effect on a
tissue, thereby preventing or retarding damage to said tissue
during transport.
[0014] Thus, one preferred method relates to preserving organs for
transplant and includes delivering to a harvested organ an
effective amount of electromagnetic energy, the electromagnetic
energy having a wavelength in the visible to near-infrared
wavelength range, wherein delivering the effective amount of
electromagnetic energy comprises selecting a predetermined power
density of electromagnetic energy. The electromagnetic energy is
applied to harvested organs placed in a preservation medium or
perfusate, and may be applied in a hypothermic environment, for
example in a hypothermic container or chamber, or in a normothermic
environment. In a preferred embodiment, the power density is
selected to be about 0.01 mW/cm.sup.2 to about 100 mW/cm.sup.2. To
deliver the predetermined power density of electromagnetic energy
to the organ, such method may further include selecting a power and
dosage of the electromagnetic energy sufficient to deliver the
predetermined power density of electromagnetic energy to the organ.
The electromagnetic energy is then applied to multiple treatment
points across the organ surface.
[0015] The methods are particularly suitable for preserving solid
organs for transplant such as heart, lung, kidney, liver, or
pancreas, but may also be used to preserve other tissues or
organs.
[0016] The methods are further directed toward preventing or
retarding rejection of a transplanted organ in a subject in need
thereof, the method including delivering to a harvested organ
before transplant into the subject an effective amount of
electromagnetic energy wherein delivering the effective amount of
electromagnetic energy comprises selecting a power density of the
electromagnetic energy, preferably about 0.01 mW/cm.sup.2 and less
than about 100 mW/cm.sup.2.
[0017] In one embodiment, an apparatus for preserving tissue, such
as a harvested organ for transplant includes a media storage
container and a primary cover which mates with the media storage
container to form a fluid-tight seal. The media storage container
has a base and side walls extending from the base, and the side
walls have a plurality of openings therethrough, each opening
configured to mate with an electromagnetic energy source, such as a
laser energy source, to form a fluid tight seal. The media storage
container is configured to suspend the harvested organ in a fluid
preservation medium. The media storage container is suspended in a
secondary container having a base and side walls extending
therefrom, the secondary container configured to suspend the media
storage container in a thermoregulatory fluid. A plurality of
electromagnetic energy sources extend from the side walls, each
electromagnetic energy source mating with one of the plurality of
openings on the media storage container side walls to form a fluid
tight seal against the thermoregulatory fluid. A secondary cover
mates with the secondary container. The electromagnetic energy
sources are configured to emit electromagnetic energy having a
wavelength in the visible to near-infrared wavelength range at a
power density selected from the range of about 1 mW/cm.sup.2 to
about 100 mW/cm.sup.2. The apparatus is used to apply
electromagnetic energy at a selected power density to a harvested
organ suspended in a preservation medium in the media storage
container.
BRIEF DESCRIPTION OF THE DRAWINGS
[0018] The FIGURE is a perspective view of one embodiment of an
apparatus for transporting tissue, such as an organ.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0019] The methods to preserve organs for transplant described
herein may be practiced and described using, for example, a low
level laser therapy apparatus such as that shown and described in
U.S. Pat. No. 6,214,035, U.S. Pat. No. 6,267,780, U.S. Pat. No.
6,273,905 and U.S. Pat. No. 6,290,714, which are all herein
incorporated by reference together with the references contained
therein. In a preferred embodiment, they are practiced using an
apparatus such as that shown in the FIGURE.
[0020] In accordance with one embodiment of method to preserve
organs for transplant is a low level laser apparatus including a
handheld probe for delivering the electromagnetic energy to the
organ. The probe includes a laser energy source emitting
electromagnetic energy having a wavelength in the visible to
near-infrared wavelength range, i.e., from about 630 nm to about
904 nm. The probe includes, for example, a single laser diode that
provides about 100 mW to about 500 mW of total power output, or
multiple laser diodes that together are capable of providing at
least about 100 mW to about 500 mW of total power output. Other
embodiments provide lower total power output, for example, about 1
mW or about 25 mW. The actual power output is preferably variable
using a control unit electronically coupled to the probe, so that
power of the light energy emitted can be adjusted in accordance
with power density calculations as described below. The diodes used
are, for example, continuously emitting CGaAlAs laser diodes having
a wavelength of about 830 nm. In one embodiment of portable
apparatus for tissue transport as described infra, a plurality of
such laser probes provide the light energy sources. Alternatively,
the electromagnetic energy source is another type of source, for
example a light-emitting diode (LED), or other light energy source,
having a wavelength in the visible to near-infrared wavelength
range. The level of coherence of a light energy source is not
critical. A light energy source need not provide light having the
same level of coherence as the light provided by a laser energy
source.
[0021] In preferred methods, the electromagnetic energy has a
wavelength in the visible to near-infrared wavelength range, and
within a select range of power density (i.e., light intensity or
power per unit area, in mW/cm.sup.2). The use of power densities
within a particular range, as noted herein, appears to be a factor
in producing beneficial effects for tissues, such as a harvested
organ, thus enhancing preservation of the organ or tissue for
transplant. In a preferred embodiment, the electromagnetic energy
delivered to an organ or tissue has a power density of about 0.01
mW/cm.sup.2 to about 100 mW/cm.sup.2 and, independent of the power
of the electromagnetic energy source used and the dosage of the
energy used, appears to improve the tissue quality of the stored
organ, and appears to enhance the preservation period of organs for
transplant. In an exemplar embodiment, the electromagnetic energy
is applied to an organ stored hypothermically, i.e., under
hypothermic arrest, or at least at a temperature below the normal
body temperature of the organ. Alternatively, the electromagnetic
energy is applied to an organ stored under normothermic conditions,
i.e., at near-normal physiologic temperature and function. Under
normothermic conditions, it is preferred that the electromagnetic
energy is applied to an organ for which a perfusion system and
gas-exchange system are supplied, such as that described in U.S.
Pat. No. 6,046,046, which is herein incorporated by reference.
[0022] In preferred embodiments, the treatment parameters include
one or more of the following and the preferred storage and
transport apparatus have light sources capable of supplying energy
having one or more of the following properties. Preferred power
densities of light at the level of the target cells of the tissue
are between about 0.01 mW/cm.sup.2 and about 100 mW/cm.sup.2,
including about 0.05, 0.1, 0.5, 1, 5, 10, 15, 20, 30, 40, 50, 60,
70, 80, and 90 mW/cm.sup.2. In other embodiments, power densities
above 100 mW/cm.sup.2, including about 250 mW/cm.sup.2 and about
1000 mW/cm.sup.2. In embodiments in which something surrounds the
tissue or organ during treatment, such as when the organ is kept in
contact with a medium such as a preservation medium or perfusate
during storage and/or transport, or where it is placed in a bag or
the like, one should take into account any possible attenuation of
the energy as it travels through such surrounding material. In most
embodiments, however, the power density emitted by the source(s)
will be substantially identical to the power density at the outside
surface of the tissue or organ. To achieve such power densities,
preferred light energy sources, each alone or in combination, are
capable of emitting light energy having a total power output of at
least about 1 mW to about 500 mW, including about 5, 10, 15, 20,
30, 50, 75, 100, 150, 200, 250, 300, and 400 mW, but may also be as
high as about 1000 mW or below 1 mW, such as 0.01 mW. Preferably
the light energy used for treatment has a wavelength in the visible
to near-infrared wavelength range, i.e., from about 630 to about
904 nm, preferably about 780 nm to about 840 nm, including about
790, 800, 810, 820, and 830 nm. The light may contain a large
number of wavelengths within this range, or it may be substantially
monochromatic (i.e. one wavelength or a very narrow band of
wavelengths).
[0023] In a preferred embodiment, the treatment proceeds
continuously during substantially the entire period of time that
the organ or tissue is being stored or transported, for example,
during the time between explantation of the tissue or organ from a
donor to implantation of the tissue or organ into a recipient,
which may be anywhere from a few minutes to several hours. During
the treatment, the light energy may be continuously provided, or it
may be pulsed. If the light is pulsed, the pulses are preferably at
least about 10 ns long, including about 100 ns, 1 ms, 10 ms, and
100 ms, and occur at a frequency of up to about 1 kHz, including
about 1 Hz, 10 Hz, 50 Hz, 100 Hz, 250 Hz, 500 Hz, and 750 Hz.
[0024] Without being bound by theory, it is believed that generally
independently of the power and dosage of the electromagnetic energy
used, electromagnetic energy delivered within a specified range of
power densities provides a biostimulative effect on mitochondria to
avoid degradation of high-energy phosphates that is known to
contribute to tissue damage. The electromagnetic energy may also
help to avoid other degradation mechanisms and/or enhance
protective mechanisms or reactions in the tissue. In any case, the
observed biostimulative effect helps to maintain cellular integrity
and prevents or retards tissue damage during compromise of the
organ's normal physiologic environment, i.e., during disruption of
normal perfusion and function such as may occur during hypothermic
or normothermic storage before transplant.
[0025] The term "organ" as used herein refers to a structure of
bodily tissue in mammal such as a human being wherein the tissue
structure as a whole is specialized to perform a particular body
function. Organs that are transplanted within the meaning of the
present methods include skin, cornea, heart, lung, kidney, liver
and pancreas. Solid organs include the heart, lung, kidney, liver
and pancreas.
[0026] The term "transplant" as used herein refers to any organ or
body tissue that has been transferred from its site of origin to a
recipient site. Specifically in an allograft transplant procedure,
the site of origin of the transplant is in a donor individual and
the recipient site is in another, recipient individual.
[0027] The term "rejection" as used herein refers to the process or
processes by which the immune response of an organ transplant
recipient mounts a reaction against the transplanted organ
sufficient to impair or destroy normal function of the organ. The
immune system response can involve specific (antibody and T
cell-dependent) or non-specific (phagocytic, complement-dependent,
etc.) mechanisms, or both.
[0028] The term "effective" as used herein refers to a
characteristic of an amount of electromagnetic energy wherein the
amount of electromagnetic energy achieves the goal of preventing,
avoiding or retarding tissue damage in tissue, such as a harvested
organ, whether the tissue damage results from ischemia,
reperfusion, degradation of high-energy phosphates, inflammatory
responses, edema, or any other tissue response to a stimulus such
as the disruption of function and the manipulation that attends
harvesting and storage of the organ.
[0029] Thus, in a broad aspect, one preferred method is directed
toward preserving a harvested organ for transplant include
delivering to the harvested organ an effective amount of
electromagnetic energy, the electromagnetic energy having a
wavelength in the visible to near-infrared wavelength range,
wherein delivering the effective amount of electromagnetic energy
comprises delivering a predetermined power density of the
electromagnetic energy to the organ. In a preferred embodiment,
delivering the predetermined power density of electromagnetic
energy to the harvested organ involves selecting the predetermined
power density to be delivered, selecting a power and dosage of the
electromagnetic energy sufficient to deliver the predetermined
power density of electromagnetic energy to the organ, and applying
the electromagnetic energy to at least one treatment point on a
surface of the organ. To deliver the predetermined power density of
electromagnetic energy to the organ, the type and size of the organ
being treated may be considered, and an appropriate dosage and
power of the electromagnetic energy selected. The appropriate
dosage and power of energy are any combination of power and dosage
sufficient to deliver the predetermined power density of
electromagnetic energy to the organ. In addition, the dosage and
power should be sufficient for the electromagnetic energy to
penetrate any body tissue such as connective tissue or fat that may
be interposed between the surface of the organ and the
electromagnetic energy source or any preservation medium or other
material that may come between the tissue and the light source(s).
Further, the selected dosage and power of the electromagnetic
energy should be sufficient to traverse any distance interposed
between the electromagnetic energy source and the surface of the
organ.
[0030] The methods and apparatus are especially suitable for
preserving for transplant any solid organ, such as a heart, a lung,
a kidney, a liver, or a pancreas. However, other tissues and other
organs such as skin and cornea may also be beneficially treated
using the methods and apparatus.
[0031] It is understood that the specific power density selected
for treating any specific harvested organ will be dependent upon a
variety of factors including especially the type (i.e., heart,
liver, etc.) and size of the organ, the wavelength of the
electromagnetic energy selected, whether the electromagnetic energy
is being applied to an organ under hypothermic; arrest or under
normothermic conditions, and the expected preservation time. Thus,
the particular power density and other treatment parameters can be
chosen to tailor the treatment to the individual organ transplant
situation as is understood and determinable by one of skill in the
art.
[0032] To deliver the selected power density of electromagnetic
energy to the interior of a harvested organ, a relatively greater
surface power density of the electromagnetic energy is calculated
taking into account any attenuation of the energy as it travels
from the energy source to a treatment point on the surface of the
organ, and through the organ tissue itself, For example, to deliver
a predetermined power density of electromagnetic energy deeply
within a relatively more massive organ such as a liver will require
a greater surface power density than to deliver the same
predetermined power density to a relatively less massive organ such
as a pancreas. Factors known to affect penetration and to be taken
into account in the calculation of the required surface power
density include pigmentation and blood content, tissue type
(myocardial, renal, etc.), and overall organ size and depth of
internal tissue relative to surface treatment points. For example,
to obtain a desired power density of about 10 mW/cm.sup.2 at a site
within an organ at a depth of 3 cm below the organ surface may
require a surface power density of 400 mW/cm.sup.2. In particular,
the higher the level of pigmentation, the higher the required
surface power density to deliver a predetermined power density of
electromagnetic energy to a subsurface site being treated
[0033] More specifically, to preserve an organ for transplant, the
electromagnetic energy source, for example a hand-held laser probe,
is sterilized and placed in contact with a treatment point on a
surface of the harvested organ. Alternatively the electromagnetic
energy source is positioned over a treatment point on the organ
surface, but held some distance away from the treatment point. A
surface power density calculation is made taking into account
factors including the wavelength of the electromagnetic energy
being used, the power density that has been selected from the power
density range of about 1 mW/cm.sup.2 to about 100 mW/cm.sup.2, the
depth of tissue being treated, the extent and type of any
intervening body tissue such as fat or connective tissue between
the energy source and the organ surface, pigmentation, and the like
that affect energy penetration and thus the power density that is
actually received at the organ treatment point and any depth
therebelow. Power of the energy source being used and the surface
area of the treatment point are accordingly adjusted to obtain a
surface power density sufficient to deliver the predetermined power
density of electromagnetic energy to the organ at a given depth
within the tissue. The electromagnetic energy source is then
energized and the selected power density of electromagnetic energy
delivered to the organ.
[0034] In an exemplary embodiment, the electromagnetic energy is
applied to at least one treatment point on the organ, the treatment
point having a diameter of about 1 cm. Thus, to most completely
treat a harvested organ which typically will have a surface area
substantially larger than a spot of a diameter of about 1 cm in
accordance with this embodiment, the electromagnetic energy is
applied sequentially to a series of multiple treatment spots having
centers that are separated by at least about 1 cm. The series of
treatment spots can be mapped out over the surface of the organ to
aid in an orderly progression of electromagnetic energy
applications that systematically cover the surface area of the
organ as it is being treated from any one approach. Some organs may
be susceptible of treatment from more than one approach, i.e.,
treatment from the frontal and rear aspects of the organ, or from
the frontal and side aspects. As the approach is changed, the
required surface power density to deliver the predetermined power
density of electromagnetic energy to the organ may change:
depending on whether and how the depth of the organ tissue being
treated relative to the organ surface changes, and any change in
the nature and extent of any intervening tissue. Alternatively, the
organ may be treated by applying the electromagnetic energy to two
or more spots simultaneously, or to the entire organ at once.
[0035] Within a preferred power density range, the precise power
density selected for treating the organ is determined according to
the judgment of a trained healthcare provider or light therapy
technician and depends on a number of factors, including the
specific wavelength of electromagnetic energy selected, and
clinical factors such as type of organ being treated, the current
survival time of the organ, the expected preservation time, whether
the organ is being preserved under hypothermic arrest or under
normothermic conditions, and the like. It should be understood that
the power density of electromagnetic energy might be adjusted as
preservation time elapses, or for use in combination with any other
preservation agent or agents, especially agents added to a
preservation medium or perfusate to achieve the desired effect of
reducing tissue damage during preservation. For example, as
preservation time elapses, it will be expected that the number
(i.e., number of treatment points) and/or frequency of
electromagnetic energy treatments should increase, and/or the
selected power density will increase to achieve the desired effect
of reducing tissue damage during preservation. Generally, as long
as the harvested organ remains viable, the electromagnetic energy
therapy can be applied on a regular basis such every quarter- or
half-hour, or hourly, or any other suitable period of time.
[0036] In another aspect, there is provided an apparatus for
preserving a harvested organ for transplant. In an exemplary
embodiment, the apparatus is a "light box," including generally a
media storage container for receiving the harvested organ and
suspending the organ in a fluid preservation medium or perfusate,
and means for applying electromagnetic energy in accordance with
the methods described above, i.e., at a selected power density, and
wavelength, to the organ therein contained. The basic configuration
of one preferred type of "light box" is, for example, described in
U.S. Pat. No. 4,951,482, which is herein incorporated by
reference.
[0037] In an exemplary embodiment, the apparatus is a portable
container suitable for hypothermic transport of donor organs, and
includes a media storage container having a base and side walls
extending from the base. The side walls have a plurality of
openings therethrough, each opening configured to mate with an
electromagnetic energy source, such as a laser probe as described
supra, or LED or other light source, to form a fluid tight seal.
The openings are configured, for example, with threads and an
O-ring type gasket, the threads configured to mate with threads on
an end of a laser probe serving as a laser energy source. The media
storage container is configured to allow for suspension of the
harvested organ in a fluid preservation medium, and a primary cover
mates with the media storage container to form a fluid-tight seal.
In this exemplary embodiment, the apparatus further includes a
secondary container having a base and side walls extending
therefrom, and is configured to suspend the media storage container
in a thermoregulatory fluid. A plurality of electromagnetic energy
sources, for example laser energy sources, extend from the side
walls of the secondary container. In one embodiment, each energy
source mates with one of the plurality of openings on the media
storage container side walls to form a fluid-tight seal against a
thermoregulatory fluid contained in the secondary container.
Similarly, the fluid-tight seal of the primary cover with the media
storage container seals inside of the media storage container
against the thermoregulatory fluid. In accordance with the methods
described herein, the energy source(s) are preferably configured to
emit light energy having one or more of the characteristics
described supra. The energy sources and organ are positioned
relative to one another so that the energy sources direct the
energy at the organ contained in the media storage container. In
one embodiment, a secondary cover mates with the secondary
container to contain a thermoregulatory fluid. The media storage
container is sized appropriately to receive and secure a large
solid organ up to about the size of an adult human liver or lung.
The secondary container is sized appropriately to receive the media
storage container and a sufficient amount of thermoregulatory fluid
to properly maintain the hypothermic arrest of the organ, while yet
remaining sufficiently compact that a single individual adult is
able to carry or otherwise transport the apparatus. It will be
appreciated that the apparatus and methods can be varied for
application to organs maintained in a normothermic environment,
e.g., in an environment at near-normal physiologic temperature
while maintaining near-normal organ function. For example, under
normothermic conditions the light energy will be applied to an
organ for which a perfusion system and gas-exchange system are
supplied, such as that described in U.S. Pat. No. 6,046,046, which
is herein incorporated by reference.
[0038] One preferred embodiment of tissue or organ transport
apparatus is illustrated in the FIGURE. The apparatus includes a
container to receive and hold the tissue or organ. The container
comprises a bottom portion 10 and a cover 12. The bottom portion 10
may be any suitable shape including, but not limited to, those
having a base and at least one wall, such as the generally
cylindrical shape illustrated in the FIGURE. The shape of the
interior of the bottom portion may or may not correspond to its
exterior shape. For example, the bottom portion of an embodiment
may have a generally cubic exterior yet have a hemispherical shaped
interior. In preferred embodiments, the exterior of the bottom
portion 10 has at least one flat surface, preferably opposite the
open end which mates with or engages the cover 12, so as to provide
a stable resting surface for the apparatus. The cover 12 is shaped
so as to mate with the bottom portion. In a preferred embodiment,
the cover 12 and bottom portion 10 form a fluid-tight seal when
placed together to aid in containment of any storage or
preservation medium or bodily fluids that may be associated with
the organ or tissue. The cover 12 and bottom portion 10 need not be
two separate, removable pieces as illustrated; they may be single
piece construction or attached together such as by a hinge or other
such mechanism. The cover 12 and bottom portion 10 may further
comprise a locking or latching mechanism, engaging threads or other
suitable means for securing the two pieces together. A handle may
also be included to assist in transporting the apparatus.
[0039] The cover 12 and/or the bottom portion 10 have at least one
light source 14 mounted thereon to provide the electromagnetic
energy to the tissue. In embodiments having more than one source
14, the light sources may be separate or a single electromagnetic
energy emitter may be used to provide light to two or more sources
14 simultaneously or in some sequence. In preferred embodiments,
the source(s) illuminate the interior from a plurality of
directions. In a preferred embodiment, the source(s) 14 is attached
to a controller (not illustrated) that is set or programmed to
deliver light having characteritics as desired for treatment,
including, but not limited to, wavelength, power, pulse duration,
pulse frequency, and, in some embodiments, to vary the treatment
parameters over time. In one embodiment, the bottom portion 10
further comprises a shelf or elevated portion upon which the organ
or tissue is placed to provide spatial separation between the organ
or tissue and one or more sources 14.
[0040] In preferred embodiments, the interior of at least the
bottom portion 10 forms a cooling chamber to allow for storage and
transport of the tissue received therein at a lowered temperature,
including temperatures sufficient to cause hypothermic arrest. The
cooling chamber is cooled by any suitable method or means. In some
preferred embodiments, one or more walls 16 of the bottom portion
have a cooling means disposed therein, including, but not limited
to, electric (or battery) powered cooling equipment (e.g. heat
pump, refrigeration, Peltier effect), thermoregulatory fluid, ice,
"blue ice", dry ice, and the like.
[0041] In another embodiment, the electromagnetic energy therapy
methods and apparatus are used to enhance growth and function of
organ-derived cell lines used in bioartificial organ support
systems such as that described in U.S. Pat. No. 5,368,555 which is
herein incorporated by reference. For example, the electromagnetic
energy is applied to a hepatic cell line that lines a hollow fiber
cartridge. Biostimulation provided to the hepatocytes or other cell
line enhances growth and function of the hepatocytes to perform key
organ-specific functions in a subject for whom organ function is
compromised. Improving the growth and function of such cell lines
as used within such bioartificial organ support systems mitigates
organ supply problems, especially for patients with acute and
substantial loss of organ function.
[0042] The explanations and illustrations presented herein are
intended to acquaint others skilled in the art with the invention,
its principles, and its practical application. Those skilled in the
art may adapt and apply the invention in its numerous forms, as may
be best suited to the requirements of a particular use.
Accordingly, the specific embodiments of the present invention as
set forth are not intended as being exhaustive or limiting of the
invention.
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