Ischemia/reperfusion protection compositions and methods of using
The invention provides for ischemia/reperfusion protection compositions having one or more ketone bodies and melatonin. The invention also provides for methods of using such compositions to reduce or prevent ischemia/reperfusion injury due to blood loss, stroke or cardiopulmonary arrest or surgery.
1. A method for treating an individual who is experiencing or has experienced blood loss, comprising administering a composition to the individual, wherein the composition comprises about 2 M to about 6 M D-beta-hydroxybutyrate or a pharmaceutically acceptable salt thereof, about 25 mM to about 80 mM melatonin or a metabolite, precursor or analog thereof, and at least one solvent.
2. The method of claim 1 , wherein the individual is experiencing or has experienced a major hemorrhagic event.
3. The method of claim 1 , wherein said blood loss in said individual results in a systolic blood pressure of about 70 mm Hg or less.
4. The method of claim 1 , 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.
5. The method of claim 1 , wherein said composition is administered intravenously.
6. The method of claim 1 , wherein said individual's StO 2 levels are less than 75%.
7. The method of claim 6 , wherein said administering results in said individual's StO 2 levels returning to greater than 75%.
8. The method of claim 6 , wherein said individual has been treated when the individual's StO 2 levels are greater than 75%.
9. The method of claim 1 , wherein said individual's lactate levels are greater than 2.1 mg/dl.
10. The method of claim 9 , wherein said administering results in said individuals lactate levels returning to less than 2.1 mg/dl.
11. The method of claim 9 , wherein said individual has been treated when the individual's lactate levels are less than 2.1 mg/dl.
12. The method of claim 1 , further comprising transfusing said individual with blood or plasma.
13. The method of claim 1 , wherein the at least one solvent is water.
14. The method of claim 13 , wherein the at least one solvent further comprises dimethyl sulfoxide (DMSO).
15. The method of claim 13 , wherein the at least one solvent further comprises ethanol.
16. The method of claim 13 , wherein the at least one solvent further comprises dimethylsulfone.
17. The method of claim 13 , wherein the at least one solvent further comprises dimethylformamide (DMF).
18. The method of claim 1 , wherein the at least one solvent comprises water and dimethyl sulfoxide (DMSO).