Methods and solutions for tissue preservation

Abstract

Described herein are compositions and methods particularly useful in the medical arts. The compositions and methods may be used in connection with the preservation of a portion of a mammal, for example, tissues, organs, appendages, limbs, extremities, stem cells, myocytes, bone marrow, skeletal muscle as well as an array of other medical procedures, such as cardiac surgery, transplantation and/or preservation. In various embodiments, the inventive composition may be hyperoxygenated and be formulated to resemble the biochemistries of natural intracellular fluids. The inventive composition includes active ingredients to reduce ischemic, hypothermic and reperfusion injury during transplantation, thereby resulting in improved post-transplant graft function and quality, when used in connection with organ transplantation and storage procedures, for example cardiac transplantation.

1 . A method of preserving a portion of a mammal, comprising:
 placing the portion of the mammal in contact with a preservation solution of  claim 17 , whereby the portion of the mammal is preserved, comprising:
 a quantity of water, and 
 a quantity of dissolved oxygen, 
   wherein the quantity of dissolved oxygen is sufficient to hyper-oxygenate the water.   
     
     
         2 - 14 . (canceled) 
     
     
         15 . A method of preserving a myocyte and/or a stem cell, comprising:
 placing the myocyte and/or stem cell in contact with a preservation solution of  claim 17 , whereby the myocyte and/or stem cell is preserved, comprising:
 a quantity of water, and 
 a quantity of dissolved oxygen, 
   wherein the quantity of dissolved oxygen is sufficient to hyper-oxygenate the water.   
     
     
         16 . (canceled) 
     
     
         17 . A tissue preservation solution adapted to preserve a portion of a mammal, comprising:
 a quantity of water;   a quantity of dissolved oxygen,   wherein the quantity of dissolved oxygen is sufficient to hyper-oxygenate the water; and   an energy source capable of being metabolized through the tricarboxylic acid cycle.   
     
     
         18 . The solution of  claim 17 , wherein the quantity of dissolved oxygen produces an oxygen tension of from about 490 mmHg to about 590 mmHg. 
     
     
         19 . (canceled) 
     
     
         20 . The solution of  claim 17 , wherein the energy source is selected from the group consisting of a quantity of glucose, a quantity of glutamate, a quantity of glutamine, a quantity of glycine and combinations thereof. 
     
     
         21 . The solution of  claim 20 , wherein the quantity of glucose is from about 19 mmol/L to about 21 mmol/L. 
     
     
         22 . The solution of  claim 20 , wherein the quantity of glutamate is from about 0.8 mmol/L to about 1.5 mmol/L. 
     
     
         23 . The solution of  claim 20 , where in the quantity of glutamine is from about 1.7 mmol/L to about 3.0 mmol/L. 
     
     
         24 . The solution of  claim 20 , wherein the quantity of glycine is from about 9.5 mmol/L to about 11.0 mmol/L. 
     
     
         25 . The solution of  claim 17 , wherein the energy source is a quantity of glucose, and the solution further comprises a quantity of insulin. 
     
     
         26 . The solution of  claim 25 , wherein the quantity of glucose is from about 19 mmol/L to about 21 mmol/L and the quantity of insulin is from about 49 U/L to about 51 U/L. 
     
     
         27 . The solution of  claim 17 , further comprising a reductant. 
     
     
         28 . The solution of  claim 27 , wherein the reductant is selected from the group consisting of allopurinol, glutathione and combinations thereof. 
     
     
         29 . The solution of  claim 28 , wherein the allopurinol is present in an amount of from about 0.8 mmol/L to about 1.2 mmol/L. 
     
     
         30 . The solution of  claim 28 , wherein the glutathione is present in an amount of from about 2.7 mmol/L to about 3.6 mmol/L. 
     
     
         31 . The solution of  claim 17 , further comprising an electrolyte. 
     
     
         32 . The solution of  claim 31 , wherein the electrolyte is formulated to resemble the biochemistry of a natural intracellular fluid. 
     
     
         33 . The solution of  claim 31 , wherein the electrolyte is selected from the group consisting of sodium chloride (NaCl), potassium chloride (KCl), magnesium sulfate (MgSO 4 ), potassium phosphate (KH 2 PO 4 /K 2 HPO 4 ), and combinations thereof. 
     
     
         34 . The solution of  claim 33 , wherein the NaCl is present in an amount of from about 3.75 mmol/L to about 4.50 mmol/L. 
     
     
         35 . The solution of  claim 33 , wherein the KCl is present in an amount of from about 115 mmol/L to about 125 mmol/L. 
     
     
         36 . The solution of  claim 33 , wherein the MgSO 4  is present in an amount of from about 2.1 mmol/L to about 2.8 mmol/L. 
     
     
         37 . The solution of  claim 33 , wherein the KH 2 PO 4 /K 2 HPO 4  is present in an amount of from about 3.5 mmol/L to about 4.0 mmol/L. 
     
     
         38 . The solution of  claim 17 , wherein the solution has an osmolarity of from about 325 mOsm to about 335 mOsm. 
     
     
         39 . The solution of  claim 17 , wherein the solution has a pH of from about 6.5 to about 7.0. 
     
     
         40 . The solution of  claim 17 , wherein the solution has a viscosity relative to water that is less than 1.5. 
     
     
         41 . The solution of  claim 17 , further comprising a quantity of adenosine. 
     
     
         42 . The solution of  claim 41 , wherein the quantity of adenosine is from about 2.5 mmol/L to about 4.0 mmol/L. 
     
     
         43 . The solution of  claim 17 , further comprising a quantity of a buffer. 
     
     
         44 . The solution of  claim 43 , wherein the buffer is 4-2-hydroxyethyl-1-piperazineethanesulfonic acid, present in an amount from about 20 mmol/L to about 21 mmol/L. 
     
     
         45 . A tissue preservation solution comprising:
 a quantity of water;   a quantity of dissolved oxygen;   an energy source capable of being metabolized through the tricarboxylic acid cycle;   a reductant; and   an electrolyte formulated to resemble the biochemistry of a natural intracellular fluid,   wherein the quantity of dissolved oxygen produces an oxygen tension of about 490 mmHg to about 590 mmHg, the osmolarity is from about 325 mOsm to about 335 mOsm, and the pH is from about 6.5 to 7.0.