Ischemia/reperfusion protection compositions and methods of using

1. A composition consisting of D-beta-hydroxybutyrate or a pharmaceutically acceptable salt thereof, melatonin or a metabolite, precursor or analog thereof, and, optionally, a pharmaceutically acceptable carrier.

2. A method for treating an individual who is experiencing or has experienced blood loss, comprising administering a composition comprising about 4 M D-beta-hydroxybutyrate or a pharmaceutically acceptable salt thereof, and about 43 mM melatonin or a metabolite, precursor or analog thereof to said individual.

3. The method of claim 2 , wherein the individual is experiencing or has experienced a major hemorrhagic event.

4. The method of claim 2 , wherein said individual has lost a blood volume of at least about 10%.

5. The method of claim 2 , wherein said individual has lost a blood volume of at least about 20%.

6. The method of claim 2 , wherein said individual has lost a blood volume of at least about 30%.

7. The method of claim 2 , wherein said blood loss in said individual results in a systolic blood pressure of about 70 mm Hg or less.

8. The method of claim 2 , wherein said D-beta-hydroxybutyrate or pharmaceutically acceptable salt thereof is administered to said individual in an amount sufficient to achieve a concentration in the blood of about 3 mM to about 15 mM, and wherein said melatonin or a metabolite, precursor or analog thereof is administered to said individual in an amount sufficient to achieve a concentration in the blood of about 20 μM to about 150 μM.

9. The method of claim 2 , wherein said composition is administered at a volume of about 0.3 to about 2 milliliters (mls) per kilogram (kg) of weight of said individual.

10. The method of claim 2 , wherein said composition is administered at a volume of about 0.3 to about 2 mLs per kg of weight of said individual per hour.

11. The method of claim 2 , wherein said composition is administered at a volume of about 0.3 to about 2 mLs per kg of weight of said individual followed by administration of said composition at a volume of about 0.3 to about 2 mLs per kg of weight of said individual per hour.

12. The method of claim 2 , wherein said composition is administered intravenously.

13. The method of claim 2 , wherein said composition is administered intraosseously.

14. The method of claim 2 , wherein said individual's StO 2 levels are less than 75%.

15. The method of claim 14 , wherein said administering results in said individual's StO 2 levels returning to greater than 75%.

16. The method of claim 2 , wherein said individual has been treated when the individual's StO 2 levels are greater than 75%.

17. The method of claim 2 , wherein said individual's lactate levels are greater than 2.1 mg/dl.

18. The method of claim 17 , wherein said administering results in said individuals lactate levels returning to less than 2.1 mg/dl.

19. The method of claim 2 , wherein said individual has been treated when the individual's lactate levels are less than 2.1 mg/dl.

20. The method of claim 2 , wherein said administering prevents the base deficit of said individual from reaching 6 mEq/L.

21. The method of claim 2 , further comprising transfusing said individual with blood or plasma.

22. The method of claim 21 , wherein said transfusing is performed after said composition is administered.

23. A method for treating an individual whose StO 2 levels are less than 75%, comprising identifying an individual whose StO 2 levels are less than 75%; and administering a composition comprising about 4 M D-beta-hydroxybutyrate or a pharmaceutically acceptable salt thereof and about 43 mM melatonin or a metabolite, precursor or analog thereof to said individual.

24. A method for treating an individual who has a base deficit level of greater than 6 mEq/L, comprising identifying an individual whose base deficit level is greater than 6 mEq/L; and administering a composition comprising D-beta-hydroxybutyrate or a pharmaceutically acceptable salt thereof and about 43 mM melatonin or a metabolite, precursor or analog thereof to said individual.

25. The composition of claim 1 , wherein said composition is substantially free of inorganic anions.

26. The composition of claim 1 , wherein said pharmaceutically acceptable salt is Na-D-beta hydroxybutyrate.

27. The composition of claim 1 , wherein said melatonin or a metabolite, precursor or analog thereof is 5-methoxy-N-acetyltryptamine.

28. The composition of claim 1 , wherein said composition is substantially free of Cl − .

29. The composition of claim 1 , further comprising a solubilizer and/or a stabilizer.

30. The composition of claim 29 , wherein said solubilizer is DMSO.

31. The composition of claim 1 , further comprising a therapeutic compound.

32. An article of manufacture comprising the composition of claim 1 .

33. A method for treating an individual who is experiencing or has experienced blood loss, comprising administering a composition consisting of D-beta-hydroxybutyrate or a pharmaceutically acceptable salt thereof, melatonin or a metabolite, precursor or analog thereof, and, optionally, a pharmaceutically acceptable carrier to said individual.

34. The method of claim 33 , wherein the individual is experiencing or has experienced a major hemorrhagic event.

35. The method of claim 33 , wherein said individual has lost a blood volume of at least about 10%.

36. The method of claim 33 , wherein said individual has lost a blood volume of at least about 20%.

37. The method of claim 33 , wherein said individual has lost a blood volume of at least about 30%.

38. The method of claim 33 , wherein said blood loss in said individual results in a systolic blood pressure of about 70 mm Hg or less.

39. The method of claim 33 , wherein said D-beta-hydroxybutyrate or pharmaceutically acceptable salt thereof is administered to said individual in an amount sufficient to achieve a concentration in the blood of about 3 mM to about 15 mM, and wherein said melatonin or analog thereof is administered to said individual in an amount sufficient to achieve a concentration in the blood of about 20 μM to about 150 μM.

40. The method of claim 33 , wherein said composition is administered at a volume of about 0.3 to about 2 milliliters (mls) per kilogram (kg) of weight of said individual.

41. The method of claim 33 , wherein said composition is administered at a volume of about 0.3 to about 2 mLs per kg of weight of said individual per hour.

42. The method of claim 33 , wherein said composition is administered at a volume of about 0.3 to about 2 mLs per kg of weight of said individual followed by administration of said composition at a volume of about 0.3 to about 2 mLs per kg of weight of said individual per hour.

43. The method of claim 33 , wherein said composition is administered intravenously.

44. The method of claim 33 , wherein said composition is administered intraosseously.

45. The method of claim 33 , wherein said individual's StO 2 levels are less than 75%.

46. The method of claim 45 , wherein said administering results in said individual's StO 2 levels returning to greater than 75%.

47. The method of claim 33 , wherein said individual has been treated when the individual's StO 2 levels are greater than 75%.

48. The method of claim 33 , wherein said individual's lactate levels are greater than 2.1 mg/dl.

49. The method of claim 48 , wherein said administering results in said individuals lactate levels returning to less than 2.1 mg/dl.

50. The method of claim 33 , wherein said individual has been treated when the individual's lactate levels are less than 2.1 mg/dl.

51. The method of claim 33 , wherein said administering prevents the base deficit of said individual from reaching 6 mEq/L.

52. The method of claim 33 , further comprising transfusing said individual with blood or plasma.

53. The method of claim 52 , wherein said transfusing is performed after said composition is administered.