Systems and Methods for Ex Vivo Organ Care

Abstract

The invention, in various embodiments, provides systems, methods and solutions for perfusing an organ ex vivo.

What is claimed: 
     
         1 . A method for evaluating a lung for transplant suitability comprising:
 positioning the lung in an ex vivo perfusion circuit,   flowing a perfusion fluid into the lung through a pulmonary artery interface and flowing the perfusion fluid away from the lung through a pulmonary vein interface, the perfusion fluid being at a physiologic temperature,   providing a gas to the lung through a tracheal interface,   measuring a first composition of a gas component in the perfusion fluid, and   performing an evaluation on the lung based on the first composition.   
     
     
         2 . The method of  claim 1 , wherein the perfusion fluid has a physiologic venous composition. 
     
     
         3 . The method of  claim 1 , wherein the flow of the gas through the tracheal interface comprises about 100% oxygen. 
     
     
         4 . The method of  claim 1 , wherein the flow of the gas through the tracheal interface comprises ambient air. 
     
     
         5 . The method of  claim 1 , wherein the evaluation includes measuring a fractional inspired oxygen concentration. 
     
     
         6 . The method of  claim 1 , wherein the evaluation includes measuring an arterial-venous (AV) oxygen gradient between the perfusion fluid flowing into the lung and the perfusion fluid flowing away from the lung. 
     
     
         7 . The method of  claim 1 , wherein the evaluation includes measuring an alveolar arterial (AA) oxygen gradient. 
     
     
         8 . The method of  claim 1 , wherein the evaluation includes measuring a tidal volume. 
     
     
         9 . The method of  claim 1 , wherein the evaluation includes measuring at least one of a level of oxygen saturation of blood hemoglobin and a partial pressure of oxygen in the perfusion fluid flowing into the lung. 
     
     
         10 . The method of  claim 1 , wherein the evaluation includes measuring at least one of a level of oxygen saturation of blood hemoglobin and a partial pressure of oxygen in the perfusion fluid flowing away from the lung. 
     
     
         11 . The method of  claim 1 , wherein the evaluation includes measuring a positive end expiratory pressure. 
     
     
         12 . The method of  claim 1 , comprising
 measuring a saturation of oxygen in the perfusion fluid flowing through the pulmonary artery interface at a plurality of times during a period of testing,   measuring a saturation of oxygen in the perfusion fluid flowing through the pulmonary vein interface at the plurality of times during the period of testing,   comparing pulmonary artery and pulmonary vein oxygen saturation measurements at each of the plurality of times to determine comparative differences at the plurality of times, and   identifying a maximum difference among the comparative differences.   
     
     
         13 . The method of  claim 12 , wherein the flow of the gas through the tracheal interface comprises about 100% oxygen. 
     
     
         14 . The method of  claim 12 , wherein the flow of the gas through the tracheal interface is less than 100% oxygen. 
     
     
         15 . The method of  claim 12 , wherein the flow of the gas through the tracheal interface is less than 75% oxygen. 
     
     
         16 . The method of  claim 15 , wherein the flow of the gas through the tracheal interface is less than 50% oxygen. 
     
     
         17 . The method of  claim 16 , wherein the flow of the gas through the tracheal interface is less than 25% oxygen. 
     
     
         18 . The method of  claim 17 , wherein the flow of the gas through the tracheal interface contains no oxygen. 
     
     
         19 . The method of  claim 1 , comprising applying a suction force through the tracheal interface to clear lung alveoli of debris. 
     
     
         20 . The method of  claim 1 , comprising causing the lung to inhale breaths that are of variable volume to clear lung alveoli of debris. 
     
     
         21 . The method of  claim 20 , wherein the breaths include a first breath having a volume that is larger than the volume of at least two next breaths. 
     
     
         22 . The method of  claim 1 , comprising
 adjusting a composition of the flow of gas to the lung after measuring the first composition of the gas component,   measuring a second composition of the gas component in the perfusion fluid after adjusting the composition of the flow of gas;   comparing the measurements of the first and second compositions of the gas component; and   performing the evaluation based on the comparison.   
     
     
         23 . A composition for use in a solution for perfusing a lung, comprising one or more carbohydrates that include dextran, and a plurality of amino acids that do not include asparagine, glutamine, or cysteine. 
     
     
         24 . The composition of  claim 23 , further comprising a blood product. 
     
     
         25 . The composition of  claim 23 , further comprising whole blood. 
     
     
         26 . The composition of  claim 25 , further comprising whole blood that has been at least partially depleted of leukocytes. 
     
     
         27 . The composition of  claim 25 , further comprising whole blood that has been at least partially depleted of platelets. 
     
     
         28 . The composition of  claim 23 , further comprising a phosphate. 
     
     
         29 . The composition of  claim 23 , further comprising insulin. 
     
     
         30 . The composition of  claim 23 , further comprising at least one vitamin. 
     
     
         31 . The composition of  claim 23 , further comprising a magnesium ion source. 
     
     
         32 . The composition of  claim 23 , further comprising one or more electrolytes. 
     
     
         33 . The composition of  claim 32 , wherein the one or more electrolytes includes potassium, sodium, calcium, chloride, sulfate, or a combination thereof. 
     
     
         34 . The composition of  claim 23 , further comprising an immunosuppressant. 
     
     
         35 . The composition of  claim 34 , further comprising a steroid. 
     
     
         36 . The composition of  claim 36 , further comprising a colloid. 
     
     
         37 . The composition of  claim 36 , wherein the colloid is selected from dextran, albumen, hyperstarch, and gelatin. 
     
     
         38 . The composition of  claim 37 , comprising dextran. 
     
     
         39 . The composition of  claim 23 , further comprising one or more therapeutic. 
     
     
         40 . The composition of  claim 36  wherein the one or more therapeutic is selected from antimicrobial, antifungal, antiviral, vasodilators, surfactants adapted to resist collapsing of alveoli within the lung, and anti-inflammatory drugs. 
     
     
         41 . The composition of  claim 36 , wherein the one or more therapeutic is a vasodilator. 
     
     
         42 . The composition of  claim 41 , wherein the vasodilator is selected from beta-1-agonist, isoproterenol and prostaglandine. 
     
     
         43 . The composition of  claim 36 , wherein the one or more therapeutic is selected from pentoxifylline, isuprel, flolan, prostacycline and a nitric oxide donor. 
     
     
         44 . The composition of  claim 43 , further comprising a nitric oxide donor selected from L-arginine, nitroglycerine, and nitroprusside. 
     
     
         45 . The composition of  claim 36 , wherein the one or more therapeutic is formulated for delivery through the tracheal interface by one of a nebulizer and a bronchoscope. 
     
     
         46 . The composition of  claim 45 , wherein the one or more therapeutic is selected from prostaglandines and brochodilators. 
     
     
         47 . The composition of  claim 23 , wherein the one or more therapeutic is beta-2 agonist. 
     
     
         48 . The composition of  claim 23 , further comprising a vector loaded with one or more genes. 
     
     
         49 . The composition of  claim 23 , further comprising an aqueous medium. 
     
     
         50 . The composition of  claim 23 , comprising:
 Calcium Chloride dihydrate   Glycine   Alanine   Arginin   Aspartic Acid   Glutamic Acid   Histidine   Isoleucine   Leucine   Methionine   Phenylalanine   Proline   Serine   Thereonine   Fryptophan   Tyrosine   Valine   L-Arginine   Lysine   Magnesium Sulfate Heptahydrate   Potassium Chloride   Sodium Chloride   Dextrose   Sodium Glycerophosphate   Insulin   MVI-Adult   SoluMedrol   Sodium Bicarbonate   
     
     
         51 . The composition of  claim 50 , comprising the following components in the following amounts per about 1000 mL of aqueous medium: 
       
         
           
                 
                 
               
                     
                 
                   Component 
                   Amount 
                 
                     
                 
                   Calcium Chloride dihydrate 
                   about 2100 mg-about 2600 mg 
                 
                   Glycine 
                   about 315 mg-about 385 mg 
                 
                   L-Alanine 
                   about 150 mg-about 200 mg 
                 
                   L-Arginine 
                   about 600 mg-about 800 mg 
                 
                   L-Aspartic Acid 
                   about 220 mg-about 270 mg 
                 
                   L-Glutamic Acid 
                   about 230 mg-about 290 mg 
                 
                   L-Histidine 
                   about 200 mg-about 250 mg 
                 
                   L-Isoleucine 
                   about 100 mg about 130 mg 
                 
                   L-Leucine 
                   about 300 mg-about 380 mg 
                 
                   L-Methionine 
                   about 50 mg-about 65 mg 
                 
                   L-Phenylalanine 
                   about 45 mg-about 60 mg 
                 
                   L-Proline 
                   about HOmg-about 140 mg 
                 
                   L-Serine 
                   about 80 mg-about 105 mg 
                 
                   L-Thereonine 
                   about 60 mg-about 80 mg 
                 
                   L-Tryptophan 
                   about 30 mg-about 40 mg 
                 
                   L-Tyrosine 
                   about 80 mg-about HOmg 
                 
                   L-Valine 
                   about 150 mg-about 190 mg 
                 
                   Lysine Acetate 
                   about 200 mg-about 250 mg 
                 
                   Magnesium Sulfate Heptahydrate 
                   about 350 mg-about 450 mg 
                 
                   Potassium Chloride 
                   about 15 mg-about 25 mg 
                 
                     
                 
             
                
                
                
               
               
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         52 . The composition of  claim 51 , further including a priming solution comprising the following components in the following relative amounts: 
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   Component 
                   Amount 
                 
                     
                     
                 
                     
                   Sodium Chloride 
                   about 4.8 g 
                 
                     
                   Potassium Chloride 
                   about 185 mg{circumflex over ( )} 
                 
                     
                   Magnesium Sulfate heptahydrate 
                   about 185 mg 
                 
                     
                   Sodium Glycerophosphate 
                   about 900 mg 
                 
                     
                     
                 
             
                
                
                
               
               
                
                
                
                
                
               
            
           
         
       
     
     
         53 . The composition of  claim 52 , wherein the priming solution further includes about 10 g to about 30 g of dextran. 
     
     
         54 . The composition of  claim 53 , wherein the priming solution further includes aqueous fluid. 
     
     
         55 . The composition of  claim 54 , wherein the components of the priming solution are in relative amounts per about 500 mL of aqueous fluid. 
     
     
         56 . The composition of  claim 23 , wherein the composition, when perfused with whole blood through a lung, prolongs the lung's ability to continue performing physiologic oxygen and carbon dioxide gas exchange ex vivo at a physiologic temperature.