A method for organ arrest, protection and preservation and reducing tissue injury

Abstract

The invention relates to compositions and methods for Inducing organ arrest, maintaining arrest and reanimating in a subject that has suffered a life threatening disease or injury; preparing, harvesting, storing organs, tissues and cells; reducing the harmful effects of at least one of anaesthesia, surgery, clinical intervention, and cardiopulmonary bypass on injuring the tissues, organs and cells of a subject; or reducing the harmful effects of surgery or clinical intervention on injuring the organs and brain in the whole body of a subject. The composition comprises (i) a compound selected from at least one of a potassium channel opener, a potassium channel agonist and an adenosine receptor agonist; (ii) an antiarrhythmic agent or a local anaesthetic; and (iii) citrate.

1 . A composition comprising (i) a compound selected from at least one of a potassium channel opener, a potassium channel agonist and an adenosine receptor agonist; (ii) an antiarrhythmic agent or a local anaesthetic; and (iii) a citrate. 
     
     
         2 . A composition according to  claim 1 , in which component (i) is an adenosine receptor agonist. 
     
     
         3 . A composition according to  claim 2 , in which the adenosine receptor agonist is adenosine or a derivative thereof. 
     
     
         4 . A composition according to  claim 23 , in which the concentration of adenosine or a derivative thereof in the composition is 0.0000001 mM to 100 mM. 
     
     
         5 . A composition according to  claim 1 , in which component (ii) is lidocaine or a derivative thereof. 
     
     
         6 . A composition according to  claim 5 , in which the concentration of lidocaine or a derivative thereof in the composition is 0.0000001 mM to 100 mM. 
     
     
         7 . A composition according to  claim 1 , in which the citrate is selected from citrate phosphate dextrose (CPD), magnesium citrate, sodium citrate, potassium citrate and sildenafil citrate. 
     
     
         8 . A composition according to  claim 1 , in which the concentration of a citrate is 0.0000001 mM to 100 mM. 
     
     
         9 . A composition according to  claim 1 , in which the composition further comprises a source of magnesium. 
     
     
         10 . A composition according to  claim 9 , in which the concentration of the source of magnesium is 2000 mM or less. 
     
     
         11 . A composition according to  claim 1 , in which the composition further comprises an anti-inflammatory agent. 
     
     
         12 . A composition according to  claim 1 , in which the composition further comprises a pharmaceutically acceptable carrier. 
     
     
         13 . A composition according to  claim 12 , in which the pharmaceutically acceptable carrier comprises a buffer. 
     
     
         14 . A composition according to  claim 1 , in which the composition further comprises an antioxidant. 
     
     
         15 . A composition according to  claim 1 , in which the composition comprises 0.1 to 40 mM of adenosine, 0.1 to 80 mM of lidocaine or a salt thereof, 0.1 to 2000 mM of a source of magnesium, 0.1 to 20 mM of a citrate and 0.9 to 3% of an ionic solution. 
     
     
         16 .- 17 . (canceled) 
     
     
         18 . A method of inducing organ arrest, maintaining arrest and reanimating in a subject that has suffered a life threatening disease or injury comprising the administration of (i) a compound selected from at least one of a potassium channel opener, a potassium channel agonist and an adenosine receptor agonist; (ii) an antiarrhythmic agent or a local anaesthetic; and (iii) a citrate to the subject. 
     
     
         19 . (canceled) 
     
     
         20 . A method for reducing the harmful effects of at least one of anaesthesia, surgery, clinical intervention and cardiopulmonary bypass on injuring the tissues, organs and cells of a subject comprising the administration of (i) a compound selected from at least one of a potassium channel opener, a potassium channel agonist and an adenosine receptor agonist; (ii) an antiarrhythmic agent or a local anaesthetic; and (iii) a citrate to the subject. 
     
     
         21 . A method according to  claim 20 , wherein the tissues, organs, and cells is a brain or heart. 
     
     
         22 . A method according to  claim 20 , in which components (i) to (iii) are administered simultaneously, sequentially or separately. 
     
     
         23 . A method according to  claim 20 , in which the administration is in one shot as a bolus or in two steps as a bolus followed by infusion.