Systems, methods, compositions and solutions for perfusing an organ

Abstract

The disclosure, in various embodiments, provides systems, methods, and solutions for perfusing an organ. The present application describes illustrative methods for perfusing an ex-vivo organ in a functioning state under physiological or near physiological conditions, including receiving an ex-vivo organ in an organ care system, the ex-vivo organ coupled to a perfusion circuit, infusing a solution into the system, combining the solution with a perfusion fluid to create a mixed solution, pumping the mixed solution to the ex-vivo organ, and receiving the mixed solution from the ex-vivo organ.

1 . A method for perfusing an ex-vivo heart, the method comprising:
 receiving an ex-vivo heart in an organ care system, wherein the ex-vivo heart is coupled to a perfusion circuit;   receiving a first solution in a first chamber of the organ care system;   receiving a second solution in a second chamber of the organ care system;   infusing, into a first fluid line in fluid communication with the first chamber and the second chamber, the first solution and the second solution;   combining, in a second fluid line of the perfusion circuit, the first solution and the second solution with a perfusion fluid to create a mixed solution; and   circulating the mixed solution through the perfusion circuit, the circulating comprising:
 pumping, via the second fluid line of the perfusion circuit, the mixed solution to the ex-vivo heart; and 
 receiving, in a third fluid line of the perfusion circuit, the mixed solution from the ex-vivo heart. 
   
     
     
         2 . The method of  claim 1 , comprising:
 receiving a priming solution in the perfusion circuit.   
     
     
         3 . The method of  claim 2 , wherein the priming solution comprises mannitol, sodium chloride, potassium chloride, magnesium sulfate heptahydrate, and sodium glycerophosphate. 
     
     
         4 . The method of  claim 2 , comprising:
 combining the priming solution with the perfusion fluid.   
     
     
         5 . The method of  claim 4 , wherein the perfusion fluid comprises whole blood or synthetic blood. 
     
     
         6 . The method of  claim 5 , comprising:
 at least partially depleting the whole blood of leukocytes or platelets before combining the perfusion fluid with the at least one of the first solution, the second solution, or the priming solution.   
     
     
         7 . The method of  claim 2 , comprising:
 circulating the priming solution through the perfusion circuit in a forward flow direction.   
     
     
         8 . The method of  claim 2 , comprising:
 circulating the priming solution through the perfusion circuit in a retrograde flow direction.   
     
     
         9 . The method of  claim 1 , wherein one of at least the first solution or the second solution comprises:
 one or more cardio stimulants comprising a catecholamine, a peptide, a polypeptide, a β1/β2-adrenoreceptor blocking agent, bupranolol, pindolol, alprenolol, a cardiac glycoside, digitalis, palustrin, or ferulic acid;   a plurality of amino acids selected from the group consisting of alanine, arginine, aspartic acid, glutamic acid, histidine, isoleucine, leucine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, and lysine that do not include asparagine, glutamine, and cysteine; and   one or more electrolytes.   
     
     
         10 . The method of  claim 1 , comprising:
 receiving a composition or a third solution comprising a component sensitive to sterilization in at least one of the first solution or the second solution after at least one of the first solution or the second solution has been sterilized.   
     
     
         11 . The method of  claim 10 , wherein the component sensitive to sterilization comprises insulin. 
     
     
         12 . The method of  claim 10 , wherein the at least one of the first solution or the second solution receives the composition or the third solution via a fourth fluid line. 
     
     
         13 . The method of  claim 1 , comprising:
 infusing the first solution or the second solution into the perfusion circuit at a rate of between about 10 mL/hr to about 40 mL/hr.   
     
     
         14 . The method of  claim 13 , comprising:
 infusing the first solution or the second solution into the perfusion circuit at a rate of about 30 mL/hr.   
     
     
         15 . The method of  claim 13 , comprising:
 infusing the first solution into the perfusion circuit at a first rate; and   infusing the second solution into the perfusion circuit at a second rate different from the first rate.   
     
     
         16 . The method of  claim 1 , comprising:
 circulating the mixed solution through the perfusion circuit at a rate of about 1 L/min.   
     
     
         17 . A method comprising:
 receiving an ex-vivo organ in an organ care system, wherein the ex-vivo organ is coupled to a perfusion circuit;   receiving a first solution in a first chamber of the organ care system;   receiving a second solution in a second chamber of the organ care system;   infusing, into the perfusion circuit, the first solution and the second solution at a rate of between about 10 mL/hr to about 40 mL/hour, wherein after the infusing, the first solution and the second solution are combined with the perfusion fluid to create a mixed solution; and   circulating a perfusion fluid through the perfusion circuit, wherein the circulating comprises:
 pumping, via a first fluid line of the perfusion circuit, the mixed solution to the ex-vivo organ; and 
   receiving, in a second fluid line of the perfusion circuit, the mixed solution from the ex-vivo organ.   
     
     
         18 . The method of  claim 17 , comprising:
 receiving a priming solution in the perfusion circuit.   
     
     
         19 . The method of  claim 18 , wherein the priming solution comprises mannitol, sodium chloride, potassium chloride, magnesium sulfate heptahydrate, and sodium glycerophosphate. 
     
     
         20 . The method of  claim 18 , wherein one of at least the first solution or the second solution comprises:
 a plurality of amino acids comprising alanine, arginine, histidine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and lysine that do not include asparagine, glutamine, and cysteine; and   one or more electrolytes.   
     
     
         21 . A method for perfusing an ex-vivo organ, the method comprising:
 receiving an ex-vivo organ in a chamber of an organ care system, wherein the ex-vivo organ is coupled to a perfusion circuit;   circulating a priming solution through the perfusion circuit;   after circulating the priming solution through the perfusion circuit, infusing a first solution and a second solution into the perfusion circuit at a rate of between about 10 mL/hr to about 40 mL/hour, wherein after the infusing, the first solution and the second solution are combined with the perfusion fluid to create a mixed solution; and   circulating a perfusion fluid through the perfusion circuit at a rate of between about 1 L/min and about 5 L/min.   
     
     
         22 . The method of  claim 21 , comprising:
 circulating the priming solution through the perfusion circuit in a forward flow direction.   
     
     
         23 . The method of  claim 21 , comprising:
 circulating the priming solution through the perfusion circuit in a retrograde flow direction.   
     
     
         24 . The method of  claim 21 , comprising:
 infusing the first solution into the perfusion circuit at a first rate; and   infusing the second solution into the perfusion circuit at a second rate different from the first rate.   
     
     
         25 . The method of  claim 21 , comprising:
 infusing the first solution or the second solution into the perfusion circuit at a rate of about 30 mL/hr.   
     
     
         26 . The method of  claim 21 , wherein the priming solution comprises mannitol, sodium chloride, potassium chloride, magnesium sulfate heptahydrate, and sodium glycerophosphate. 
     
     
         27 . The method of  claim 21 , wherein one of at least the first solution or the second solution comprises:
 one or more cardio stimulants comprising a catecholamine, a peptide, a polypeptide, a β1/β2-adrenoreceptor blocking agent, bupranolol, pindolol, alprenolol, a cardiac glycoside, digitalis, palustrin, and ferulic acid;   a plurality of amino acids selected from the group comprising alanine, arginine, aspartic acid, glutamic acid, histidine, isoleucine, leucine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, and lysine that do not include asparagine, glutamine, and cysteine; and   one or more electrolytes.