Compositions and methods for organ preservation

Abstract

Disclosed herein are solutions for use with machine perfusion of one or more organs. In some embodiments, the solutions comprise acellular cross-linked hemoglobin in a physiologically acceptable medium. Also disclosed herein are methods for machine perfusion of one or more organs, for example utilizing the disclosed perfusion solutions. In some embodiments, the methods include perfusing an organ with an oxygenated solution (such as the disclosed solutions) which is at a temperature between about 12-37° C., for example at a temperature of about 21° C.

1 - 2 . (canceled) 
     
     
         3 . An organ perfusion solution comprising 3-4 g/dL acellular cross-linked hemoglobin and 10-40 g/L hydroxyethyl starch in a physiologically acceptable medium, wherein the solution has a pH of about 7.55-7.85 at room temperature, an osmolality of about 290-300 mOsm/kg, and a colloid osmotic pressure of about 35-65 mm Hg. 
     
     
         4 . The solution of  claim 3 , wherein the solution has a pH of about 7.6-7.7, an osmolality of about 295-297, and a colloid osmotic pressure of about 58-60. 
     
     
         5 . The solution of  claim 3 , wherein the cross-linked hemoglobin comprises cross-linked bovine hemoglobin having an average molecular weight of about 200-270 kD. 
     
     
         6 . The solution of  claim 5 , wherein the cross-linked bovine hemoglobin comprises cross-linked hemoglobin having an average molecular weight of about 250 kD. 
     
     
         7 . The solution of  claim 6 , wherein the cross-linked bovine hemoglobin is glutaraldehyde cross-linked hemoglobin. 
     
     
         8 - 9 . (canceled) 
     
     
         10 . The solution of  claim 3 , wherein the physiologically acceptable medium comprises about 100-140 mM sodium ions, about 8-18 mM potassium ions, about 30-90 mM chloride ions, and about 0.2-0.7 mM calcium ions. 
     
     
         11 . The solution of  claim 10 , wherein the physiologically acceptable medium comprises about 100-110 mM sodium ions, about 15-18 mM potassium ions, about 30-40 mM chloride ions, and about 0.2-0.3 mM calcium ions. 
     
     
         12 - 13 . (canceled) 
     
     
         14 . The solution of  claim 3 , further comprising one or more of a reducing agent, a buffer, an antibiotic, insulin, dexamethasone, or a combination thereof. 
     
     
         15 . The solution of  claim 14 , wherein the reducing agent comprises glutathione, N-acetyl-L-cysteine, or a combination thereof. 
     
     
         16 . The solution of  claim 3 , comprising 3-4 g/dL cross-linked hemoglobin, 25-85 mM NaCl, 1-3 mM KCl, 6-20 mM KH 2 PO 4 , 20-70 mM sodium gluconate, 5-21 mM sodium lactate, 1-4 mM magnesium gluconate, 0.6-1.2 mM CaCl 2  dihydrate, 11-16 mM NaOH, 1-4 mM adenine, 2-8 mM dextrose, 0.5-3 mM glutathione, 2-8 mM HEPES, 1-4 mM ribose, 7-30 mM mannitol, 10-40 g/L hydroxyethyl starch, and 40-160 mg/dL N-acetyl-L-cysteine. 
     
     
         17 . The solution of  claim 16 , comprising 3-4 g/dL cross-linked hemoglobin, 25-30 mM NaCl, 1-2 mM KCl, 17-19 mM KH 2 PO 4 , 55-65 mM sodium gluconate, 6-8 mM sodium lactate, 3-4 mM magnesium gluconate, 0.6-0.8 mM CaCl 2  dihydrate, 15-16 mM NaOH, 3-4 mM adenine, 6-8 mM dextrose, 2-3 mM glutathione, 6-8 mM HEPES, 3-4 mM ribose, 20-25 mM mannitol, 35-40 g/L hydroxyethyl starch, and 40-60 mg/dL N-acetyl-L-cysteine. 
     
     
         18 . The solution of  claim 17 , comprising about 3.25 g/dL cross-linked hemoglobin, 28.25 mM NaCl, 1 mM KCl, 18.75 mM KH 2 PO 4 , 60 mM sodium gluconate, 6.75 mM sodium lactate, 3.75 mM magnesium gluconate, 0.725 mM CaCl 2  dihydrate, 15.62 mM NaOH, 3.75 mM adenine, 7.5 mM dextrose, 2.25 mM glutathione, 7.5 mM HEPES, 3.75 mM ribose, 22.5 mM mannitol, 37.5 g/L hydroxyethyl starch, and 50 mg/dL N-acetyl-L-cysteine. 
     
     
         19 - 23 . (canceled) 
     
     
         24 . The solution of  claim 3 , wherein the solution is oxygenated with a gas mixture having an FiO 2  of 40-80%. 
     
     
         25 . The solution of  claim 24 , wherein the solution is oxygenated with a gas mixture having an FiO 2  of about 60%. 
     
     
         26 - 30 . (canceled) 
     
     
         31 . An organ perfusion apparatus comprising a perfusion liquid reservoir, wherein the reservoir comprises the solution of  claim 3 . 
     
     
         32 . (canceled)