Method for ex-vivo organ care and for using lactate as an indication of donor organ status

• US 8,304,181 B2
• Filed: 04/25/2007
• Issued: 11/06/2012
• Est. Priority Date: 10/07/2004
• Status: Active Grant

• Current Assignee: TransMedics, Inc. (TransMedics Group, Inc.)
• Original Assignee: TransMedics, Inc. (TransMedics Group, Inc.)
• Inventors: Hassanein, Waleed, Khayal, Tamer, Elbetanony, Ahmed, Lezberg, Paul, Cecere, Giovanni, Sousa, Dennis, Hansen, Elizabeth
• Primary Examiner(s): FORD, ALLISON M
• Application Number:
  US11/790,405
• Publication Number:
  US 20070275364A1
• Time in Patent Office: 2,022 Days
• Field of Search: None
• US Class Current: 435/1.1
• CPC Class Codes: A01N 1/02 Preservation of living parts
• CPC Class Codes: A01N 1/0247 for perfusion, i.e. for circulating fluid through organs, blood vessels or other living parts

Abstract

The invention provides, in various embodiments, systems, devices and methods relating to ex-vivo organ care. In certain embodiments, the invention relates to maintaining an organ ex-vivo at near-physiologic conditions. The present application describes a method for using lactate measurement in the arterial and the venous blood lines of the Organ Care System Heart perfusion device to evaluate the: 1) The overall perfusion status of an isolated heart and 2) The metabolic status of an isolated heart and 3) the overall vascular patency of an isolated donor heart. This aspect of the present invention uses the property of myocardial cell'"'"'s unique ability to produce/generate lactate when they are starved for oxygen and metabolize/utilize lactate for energy production when they are well perfused with oxygen.

Claims

1. A method of evaluating an ex vivo heart for transplantation suitability comprising:

a) placing a heart in a protective chamber of an organ care system,

b) connecting the heart to a perfusion fluid circuit to perfuse fluid to the heart,

c) pumping a perfusion fluid to the heart,

d) monitoring lactate in the heart to assess heart status, said monitoring comprising;

i) measuring a first lactate value of the perfusion fluid in an arterial conduit,

ii) measuring a first lactate value of the perfusion fluid in a venous conduit, and

iii) comparing the first lactate value in the arterial conduit to the first lactate value in the venous conduit to measure a first V-A lactate differential;

iv) repeating steps i)-iii) one or more additional times, at later points in time, to measure subsequent V-A lactate differentials over time;

e) correlating the change between the V-A lactate differentials over time with suitability of the heart for transplantation.

2. The method of claim 1, wherein the V-A lactate differentials are measured at regular intervals.

3. The method of claim 1, wherein the first V-A lactate differential is measured about 60 minutes or less prior to measuring a second V-A lactate differential.

4. The method of claim 1 wherein the total length of time that the lactate values are monitored is more than one hour.

5. The method of claim 1, further comprising:

f) measuring the perfusion pressure in the arterial conduit.

6. The method of claim 5, further comprising:

g) correlating the perfusion pressure in the arterial conduit and the change in the V-A lactate differentials over time to coronary vascular patency of the heart.

7. A method of evaluating an ex vivo heart for transplantation suitability comprising:

a) placing a heart in a protective chamber of a portable organ care system,

b) flowing a perfusion fluid in a conduit circuit including the heart,

c) measuring a lactate value of the perfusion fluid in an arterial conduit,

d) measuring a lactate value of the perfusion fluid in a venous conduit,

e) comparing the lactate value in the arterial conduit to the lactate value in the venous conduit to obtain a first V-A lactate differential,

f) repeating steps c)-e) at a later point in time to obtain a second V-A lactate differential, and

g) correlating the change between the first V-A lactate differential and the second V-A lactate differential to the suitability of the heart for transplant.

8. The method of claim 7, further comprising:

h) measuring the perfusion pressure in the arterial conduit.

9. The method of claim 8, further comprising:

i) correlating the perfusion pressure in the arterial conduit and the change in the V-A lactate differentials over time to coronary vascular patency of the heart.

10. A method for evaluating an ex vivo heart for transplantation suitability comprising:

a) placing a heart in a protective chamber of an organ care system,

b) pumping a perfusion fluid into the heart via a retrograde perfusion of an aorta of the heart,

c) providing a flow of the perfusion fluid away from the heart via a right ventricle of the heart,

d) measuring a lactate value of the fluid leading to the aorta of the heart,

e) measuring a lactate value of the fluid leading away from the right ventricle of the heart,

f) comparing the lactate value of the fluid leading to the aorta to the lactate value of the fluid leading away from the right ventricle to obtain a first V-A lactate differential,

g) repeating steps c)-f) at a later point in time to obtain a second V-A lactate differential, and

h) correlating the change between the first V-A lactate differential and the second V-A lactate differential to the suitability of the heart for transplant.

11. The method of claim 10, wherein step f) involves subtracting the lactate value of the perfusion fluid leading to the aorta of the heart from the lactate value of the perfusion fluid leading away from the heart to determine the V-A lactate differential.

12. The method of claim 10, further comprising:

i) measuring the pressure of the fluid leading to the aorta of the heart.

13. A method for evaluating an ex vivo heart for transplantation suitability comprising:

a) placing a heart in a protective chamber of an organ care system,

b) pumping a perfusion fluid into the heart via an arterial conduit,

c) providing a flow of the perfusion fluid away from the heart via a venous conduit,

d) measuring the lactate value of the fluid leading to the heart,

e) measuring the lactate value of the fluid leading away from the heart,

f) comparing the lactate value of the fluid leading to the heart to the lactate value leading away from the heart to obtain a first V-A lactate differential;

g) repeating steps d)-f) at a later point in time to obtain a second V-A lactate differential; and

h) correlating the change between the first V-A lactate differential and the second V-A lactate differential to suitability of the heart for transplant.

14. The method of claim 13, wherein step f) involves subtracting the lactate value of the perfusion fluid leading to the aorta of the heart from the lactate value of the perfusion fluid leading away from the heart to determine the V-A lactate differential.

15. The method of claim 13 further comprising:

i) measuring the pressure of the fluid leading to the aorta of the heart, and

j) correlating the pressure of the fluid leading to the heart and the change in the V-A lactate differentials over time to suitability of the heart for transplantation.

16. A method for evaluating an ex vivo heart for transplantation suitability, said method comprising:

a) placing a heart in a protective chamber of an organ care system,

b) maintaining the heart in a functioning and viable state, said maintaining including

(i) perfusing the heart with a perfusion fluid,

(ii) measuring a lactate value of the perfusion fluid in an arterial conduit,

(iii) measuring a lactate value of the perfusion fluid in a venous conduit,

(iv) comparing the lactate value in the arterial conduit to the lactate value in the venous conduit to obtain a first V-A lactate differential,

(v) repeating steps (ii)-(iii) at a later point in time to obtain a second V-A lactate differential,

c) correlating the change between the first V-A lactate differential and the second lactate V-A differential to the suitability of a heart for transplant.

17. The method of claim 16, wherein the V-A lactate differentials are measured at a regular intervals.

18. The method of claim 17 wherein the regular interval is less than about 60 minutes.

19. The method of claim 17 wherein the total length of time that the lactate values are measured is more than one hour.

20. A method of evaluating an ex vivo heart for transplantation comprising:

a) placing a heart in a protective chamber of an organ care system,

b) connecting the heart to a perfusion fluid circuit to perfuse fluid to the heart,

c) pumping a perfusion fluid through the heart,

d) measuring a first lactate value of the perfusion fluid in an arterial conduit,

e) measuring a first lactate value of the perfusion fluid in a venous conduit,

f) comparing the lactate value in the arterial conduit to the lactate value in the venous conduit to obtain a first V-A lactate differential;

g) repeating steps d)-f) at a later point in time to obtain a second V-A lactate differential, and

h) correlating the change between the first V-A lactate differential and the second V-A lactate differential to the suitability of the heart for transplantation.

21. The method of claim 20, wherein the later point in time is 60 minutes or less.