Methods and compositions comprising a nitrite-reductase promoter for treatment of medical disorders and preservation of blood products
The invention provides methods, compositions, and medical kits comprising a nitrite-reductase promoter, such as an allosteric modulator of hemoglobin, for use in treating medical disorders and preservation of blood products. In one aspect, the invention provides methods, compositions, and medical kits comprising an inorganic nitrite salt and a nitrite-reductase promoter, such as an allosteric modulator of hemoglobin, for use in treating medical disorders, such as cancer, cardiovascular disorders, ischemic conditions, hemolytic conditions, and bacterial infections. Exemplary inorganic nitrite salts include sodium nitrite and arginine nitrite. Exemplary allosteric modulators of hemoglobin described herein include alkyl-substituted and acyl-substituted di-nitroheterocycles.
1. A method of treating a patient suffering from hemorrhagic shock, comprising:
administering to a patient in need thereof whole blood and a therapeutic agent, wherein the patient receives, by intravenous injection, a single composition comprising the whole blood and the therapeutic agent, wherein the therapeutic agent is:
or a pharmaceutically acceptable salt or solvate thereof, and
wherein administering the whole blood and the therapeutic agent achieves an improved systemic and microvascular hemodynamic response compared to a blood transfusion, with or without nitrite supplementation.
2. The method of claim 1 , wherein the therapeutic agent is
3. A method of performing a blood transfusion to a patient suffering from hemorrhagic shock, comprising:
administering to a patient in need thereof a whole blood and a therapeutic agent, wherein the patient receives, by intravenous injection, a single composition comprising the whole blood and the therapeutic agent, wherein the therapeutic agent is:
or a pharmaceutically acceptable salt or solvate thereof, and
wherein administering the whole blood and the therapeutic agent achieves an improved systemic and microvascular hemodynamic response compared to a blood transfusion, with or without nitrite supplementation.
4. The method of claim 3 , further comprising administering an alkali metal nitrite to the patient.
5. The method of claim 3 , further comprising administering sodium nitrite to the patient.
6. The method of claim 3 , wherein the therapeutic agent is