SYSTEMS AND METHODS FOR EX VIVO LUNG CARE

• US 20090197292A1
• Filed: 04/08/2008
• Published: 08/06/2009
• Est. Priority Date: 01/31/2008
• Status: Active Grant

• Current Assignee: TransMedics, Inc. (TransMedics Group, Inc.)
• Original Assignee: TransMedics, Inc. (TransMedics Group, Inc.)
• Inventors: Sullivan, John, Murray, Paul, Kyi, Stanley, Fattah, Ihab Abdel, Havener, Robert, Hassanein, Waleed, Khayal, Tamer, Newell, Scott, Anderson, Mark, Bringham, Richard, Fishman, Robert, Van Driel, Michael, De Remer, Matthew, Bishop, Tom, Taylor, Ron, Harriott, Doug, Abdelazim, Anas
• Granted Patent: US 10,750,738 B2
• Time in Patent Office: Days
• US Class Current: 435/29
• CPC Class Codes: A01N 1/02 Preservation of living parts
• CPC Class Codes: A01N 1/021 Preservation or perfusion media, liquids, solids or gases used in the preservation of cells, tissue, organs or bodily fluids
• CPC Class Codes: A01N 1/0247 for perfusion, i.e. for circulating fluid through organs, blood vessels or other living parts

Abstract

Methods and systems of maintaining, evaluating, and providing therapy to a lung ex vivo. The methods and systems involve positioning the lung in an ex vivo perfusion circuit; circulating a perfusion fluid through the lung, the fluid entering the lung through a pulmonary artery interface and leaving the lung through a left atrial interface; and ventilating the lung by flowing a ventilation gas through a tracheal interface. Maintaining the lung for extended periods involves causing the lung to rebreath a captive volume of air, and reaching an equilibrium state between the perfusion fluid and the ventilation gas. Evaluating the gas exchange capability of the lung involves deoxygenating the perfusion fluid and measuring a time taken to reoxygenate the perfusion fluid by ventilating the lung with an oxygenation gas.

Claims

1. A method of evaluating a lung comprising:

circulating a perfusion fluid through the lung, the fluid entering the lung through a pulmonary artery interface and leaving the lung through a left atrial interface;

ventilating the lung by flowing a ventilation gas through a tracheal interface;

deoxygenating the perfusion fluid until a predetermined first value of oxygen content in the perfusion fluid is reached; and

reoxygenating the perfusion fluid by ventilating the lung with an oxygenation gas until a predetermined second value of oxygen content in the perfusion fluid is reached, wherein a condition of the lung can be determined based on a time taken for the lung to cause the oxygen content in the perfusion fluid to change from the first value of oxygen content to the second value of oxygen content.

2. The method of claim 1, wherein the perfusion fluid is deoxygenated by ventilating the lung with a deoxygenation gas comprising CO₂.

3. The method of claim 2 wherein the deoxygenation gas comprises about 6% CO₂.

4. The method of claim 1, wherein the perfusion fluid is deoxygenated by circulating the perfusion fluid through a gas exchange device, the gas exchange device being in fluid communication with a deoxygenation gas comprising CO₂ and N₂, the gas exchange device removing oxygen from the perfusion fluid by gas exchange between the deoxygenation gas and the perfusion fluid.

5. The method of claim 4, wherein the deoxygenation gas comprises about 6% CO₂ and about 94% N₂.

6. The method of claim 1, wherein the perfusion fluid is deoxygenated by ventilating the lung with a deoxygenation gas comprising CO₂ and N₂.

7. The method of claim 1, wherein the perfusion fluid contains red blood cells and the predetermined first value of oxygen content in the perfusion fluid corresponds to about a 73% saturation of the red blood cells

8. The method of claim 1, wherein the perfusion fluid contains red blood cells and the predetermined second value of oxygen content in the perfusion fluid corresponds to about a 93% saturation of the red blood cells.

9. The method of claim 1, wherein the oxygenation gas is air.

10. The method of claim 1, wherein the oxygenation gas contains between about 25% and 100% oxygen.

11. The method of claim 1, wherein the perfusion fluid flows through the perfusion circuit at a rate of about 1.5 liters per minute.

12. The method of claim 1, wherein the lung is evaluated while the lung is being transported.

13. The method of claim 1, wherein the perfusion fluid is maintained at a near physiologic temperature.

14. The method of claim 1, wherein the perfusion fluid comprises a blood product.

15. The method of claim 14, wherein the perfusion fluid is at least partially depleted of leukocytes.

16. The method of claim 14, wherein the perfusion fluid is at least partially depleted of platelets.

17. The method of claim 1, wherein the perfusion fluid comprises whole blood.

18. The method of claim 1, further comprising delivering one or more therapeutics to the lung during perfusion.

19. The method of claim 18, wherein the one or more therapeutics are selected from antimicrobials, vasodilators, and anti-inflammatory drugs.

20. The method of claim 18, wherein the one or more therapeutics are selected from the group consisting of prostaglandins, prostacyline, dextran, isuprel, flolan, and nitric oxide donors.

21. The method of claim 18, wherein the one or more therapeutics are delivered through the tracheal interface through one of a nebulizer and a bronchoscope.

22. The method of claim 1 further comprising measuring an oxygen content of the perfusion fluid to determine when the first and second predetermined values of oxygen content in the perfusion fluid are reached.

23. The method of claim 22, wherein the oxygen content of the perfusion fluid is measured by determining a saturation level of red blood cells in the perfusion fluid using a pulse oxymeter.

24. A system for evaluating a lung comprising:

an ex vivo perfusion circuit for circulating a perfusion fluid through the lung, the fluid entering the lung through a pulmonary artery interface and leaving the lung through a left atrial interface; and

a ventilation circuit for flowing a ventilation gas into and out of the lung through a tracheal interface, wherein the system is configured to deoxygenate the perfusion fluid until a predetermined first value of oxygen content in the perfusion fluid is reached and to reoxygenate the perfusion fluid by ventilating the lung with an oxygenation gas until a predetermined second value of oxygen content in the perfusion fluid is reached, and wherein the system is further configured to determine a condition of the lung based on a time taken for the lung to cause the oxygen content in the perfusion fluid to change from the first value of oxygen content to the second value of oxygen content.

25. The system of claim 24, wherein the system is configured to deoxygenate the perfusion fluid by ventilating the lung with a deoxygenation gas comprising CO₂ and N₂.

26. The system of claim 24, wherein the ventilation circuit further includes a gas exchange device, and the system is configured to deoxygenate the perfusion fluid by circulating the perfusion fluid through the gas exchange device while passing a deoxygenation gas comprising CO₂ and N₂ through the gas exchange device, the gas exchange device being adapted to remove oxygen from the perfusion fluid by gas exchange between the deoxygenation gas and the perfusion fluid.

27. A system for evaluating a lung comprising:

means for circulating a perfusion fluid through the lung, the fluid entering the lung through a pulmonary artery interface and leaving the lung through a left atrial interface; and

means for flowing a ventilation gas into and out of the lung through a tracheal interface, wherein the system is configured to deoxygenate the perfusion fluid until a predetermined first value of oxygen content in the perfusion fluid is reached and to reoxygenate the perfusion fluid by ventilating the lung with an oxygenation gas until a predetermined second value of oxygen content in the perfusion fluid is reached, and wherein the system is further configured to determine a condition of the lung based on a time taken for the lung to cause the oxygen content in the perfusion fluid to change from the first value of oxygen content to the second value of oxygen content.

28. A lung care system comprising:

an ex vivo perfusion circuit for circulating a perfusion fluid through the lung, the fluid entering the lung through a pulmonary artery interface and leaving the lung through a left atrial interface; and

a ventilation circuit for flowing a ventilation gas into and out of the lung through a tracheal interface,

wherein the system includes a lung maintenance mode and a lung evaluation mode,

the lung maintenance mode being configured to ventilate the lung through the tracheal interface by flowing a captive volume of a ventilation gas back and forth between the lung and a variable volume chamber, and

the evaluation mode being configured to;

deoxygenate the perfusion fluid until a predetermined first value of oxygen content in the perfusion fluid is reached;

reoxygenate the perfusion fluid by ventilating the lung with an oxygenation gas until a predetermined second value of oxygen content in the perfusion fluid is reached; and

determine a condition of the lung based on a time taken for the lung to cause the oxygen content in the perfusion fluid to change from the first value of oxygen content to the second value of oxygen content.