Systems And Methods To Improve Organ Or Tissue Function And Organ Or Tissue Transplant Longevity

Abstract

The present invention provides for systems and methods for inhaled CO therapy to prevent, attenuate, or delay processes that accelerate the loss of organ or tissue function, thereby increasing the lifespan of transplanted organs or tissues, or slowing the decline of native organs or tissues, or delaying the need for replacement of diseased native organs with organ transplants. Such biological processes that are prevented, attenuated, or delayed include chronic persistent inflammation, fibrosis, scarring, as well as immunologic or autoimmune attack.

1 - 40 . (canceled) 
     
     
         41 . A method for the combined administration and monitoring of carbon monoxide (CO), the method comprising (a) administering CO to a patient or organ, (b) measuring or monitoring CO levels and/or one or more CO markers, and (c) adjusting the CO administration based on the measuring or monitoring of CO levels and/or one or more CO markers. 
     
     
         42 . The method of  claim 41 , wherein the CO is administered to an organ ex vivo. 
     
     
         43 . The method of  claim 42 , wherein the organ is in preservation or storage media comprising about 50 to about 2,000 ppm CO. 
     
     
         44 . The method of  claim 43 , wherein the media comprises about 50 to about 500 ppm CO. 
     
     
         45 . The method of  claim 42 , wherein gas comprising about 50 ppm to about 2,000 ppm CO is bubbled into the media. 
     
     
         46 . The method of  claim 45 , further comprising bubbling one or more of O 2 , NO or N 2  into the media. 
     
     
         47 . The method of  claim 45 , wherein the CO is bubbled into the media before the organ is placed in the media. 
     
     
         48 . The method of  claim 45 , wherein the CO is bubbled into the media when the organ is first placed in the media or shortly thereafter. 
     
     
         49 . The method of  claim 43 , wherein the media comprises one or more of adenine-containing cold preservation buffer, lactobionate/raffinose solution or Histidine-Tryptophan Ketoglutarate. 
     
     
         50 . The method of  claim 43 , wherein the media comprises one or more of Celsior® solution, Perfadex® solution, Euro-collins solution, and modified Euro-Collins solution. 
     
     
         51 . The method of  claim 42 , wherein the organ undergoes machine perfusion with oxygen supplementation. 
     
     
         52 . The method of  claim 51 , wherein the oxygen supplementation includes one or more of O 2 , NO, N 2  and/or other gases. 
     
     
         53 . The method of  claim 42 , wherein the organ comprises one or more of kidney, lung, heart, liver, pancreas, bone marrow, gastrointestinal tract, and skin. 
     
     
         54 . The method of  claim 41 , wherein the CO is administered to a patient by an extracorporeal perfusion machine. 
     
     
         55 . The method of  claim 54 , wherein the patient is an organ or tissue transplant recipient. 
     
     
         56 . The method of  claim 55 , wherein the organ or tissue comprises one or more of kidney, liver, lung, pancreas, heart, bone marrow, intestinal tissue, and skin. 
     
     
         57 . The method of  claim 54 , wherein the concentration of CO is about 50 ppm to about 500 ppm. 
     
     
         58 . The method of  claim 41 , wherein the CO marker comprises carboxyhemoglobin (CO-Hb). 
     
     
         59 . The method of  claim 58 , further comprising administering the CO until CO-Hb concentration levels reach about 6% to about 15%. 
     
     
         60 . The method of claim  1 , wherein the CO is provided by gas source tank.