METHOD AND APPARATUS FOR ADMINISTERING NITRIC OXIDE WITH SUPPLEMENTAL DRUGS

1 . A method of providing a therapeutic composition comprising:

administering a ROS reducing drug;

administering exogenous nitric oxide; and

reducing symptoms of oxidative stress and/or fibrosis in a patient.

2 . The method of claim 1 further comprising

mixing a first gas including oxygen and a second gas including a nitric oxide-releasing agent within a receptacle to form a gas mixture, wherein the receptacle includes an inlet, an outlet and a reducing agent; and

contacting the nitric oxide-releasing agent in the gas mixture with the reducing agent to generate nitric oxide

3 . The method of claim 1 wherein administering exogenous NO is in combination with a prostacyclin drug, anti-fibrotic drug, anti-hypertensive drug, or calcium channel blocker.

4 . The method of claim 1 wherein the exogenous NO is inhaled.

5 . The method of claim 1 wherein the symptoms of oxidative stress include memory loss and/or brain fog.

6 . The method of 1 , wherein the symptoms of oxidative stress include fatigue.

7 . The method of 1 , wherein the symptoms of oxidative stress include muscle and/or joint pain.

8 . The method of 1 , wherein the symptoms of oxidative stress include decreased eye sight.

9 . The method of claim 1 wherein the symptoms of oxidative stress include headaches and sensitivity to noise.

10 . The method of claim 1 wherein the symptoms of oxidative stress include susceptibility to infections.

11 . The method of claim 1 , wherein the nitric oxide-releasing agent is nitrogen dioxide.

12 . The method of claim 1 , further comprising delivering a hydrogen gas.

13 . The method of claim 12 , wherein the hydrogen acts to eliminate peroxynitrite, thereby reducing adverse effects of nitric oxide.

14 . The method of claim 1 , wherein the ROS is a result of a disease.

15 . The method of claim 1 , wherein the ROS is drug-induced.

16 . The method of any one of claim 1 , wherein the second gas includes an inert gas or oxygen.

17 . The method of claim 1 , wherein the concentration of nitric oxide in the gas mixture delivered is at least 0.01 ppm and at most 2 ppm.

18 . The method of claim 1 , wherein the patient is treated for symptoms of interstitial lung disease, oxygen-induced inflammation, cardiac ischemia, myocardial dysfunction, ARDS, pneumonia, pulmonary embolism, COPD, emphysema, fibrosis, sleep apnea or mountain sickness due to high altitude.

19 . The method of claim 2 , wherein delivering the gas mixture including nitric oxide from the receptacle to the mammal includes passing the gas mixture through a delivery conduit located between the receptacle and a patient interface.

20 . The method of claim 19 , wherein the volume of the receptacle is greater than the volume of the delivery conduit.

21 . The method of claim 19 , wherein the volume of the receptacle is at least two times the volume of the delivery conduit.

22 . The method of claim 2 , wherein delivering the gas mixture including nitric oxide from the receptacle to the mammal includes intermittently providing the gas mixture to the mammal.

23 . The method of claim 2 , wherein delivering the gas mixture including nitric oxide from the receptacle to the mammal includes pulsing the gas mixture.

24 . The method of claim 23 , wherein pulsing includes providing the gas mixture for one or more pulses of 1 to 6 seconds.

25 . The method of claim 23 , wherein the volume of the receptacle is greater than the volume of the gas mixture in a pulse.

26 . The method of claim 23 , wherein the volume of the receptacle is at least twice the volume of the gas mixture in a pulse.

27 . The method of claim 23 , wherein the gas mixture is stored in the receptacle between pulses.

28 . The method of claim 2 , comprising storing the gas mixture in the receptacle for a predetermined period of time, and wherein the predetermined period is at least 1 second.

29 . The method of claim 23 , wherein pulsing includes providing the gas mixture for two or more pulses and the concentration of nitric oxide in each pulse varies by less than 10%.

30 . The method of claim 23 , wherein pulsing includes providing the gas mixture for two or more pulses and the concentration of nitric oxide in each pulse varies by less than 10 ppm.

31 . The method of claim 2 , comprising communicating the first gas through a gas conduit to the receptacle and supplying the second gas into the gas conduit immediately prior to the receptacle.

32 . The method of claim 2 , comprising supplying the second gas at the receptacle.

33 . The method of claim 1 , further comprising administering exogenous NO in an amount effective to modulate the hormesis characteristics of NO.

34 . The method of claim 1 wherein the nitric oxide is provided in an effective amount to minimize hemolysis during sepsis.

35 . The method of claim 1 , wherein the nitric oxide is administered to neonates.

36 . The method of claim 1 , wherein the nitric oxide is administered to pediatric patients.

37 . The method of claim 1 , wherein the nitric oxide is administered to adults.

38 . The method of claim 1 , wherein the nitric oxide is provided through a cartridge having a length, width, and thickness, an outer surface, and an inner surface, and can be substantially cylindrical in shape.

39 . The method of claim 38 , wherein the thickness between the inner and outer surface is constant, thereby providing a uniform exposure to the reducing agents.

40 . The method of claim 38 , wherein the cartridge is configured to utilize the whole surface area in converting nitric oxide-releasing agents to NO.

41 . A method of providing a therapeutic composition comprising:

administering an anti-fibrotic drug;

administering inhaled nitric oxide; and

reducing symptoms of oxidative stress and/or fibrosis in a patient.

42 . A method of providing a therapeutic composition comprising:

administering a calcium channel blocker;

administering inhaled nitric oxide; and

reducing symptoms of oxidative stress and/or fibrosis in a patient.

43 . A method of providing a therapeutic composition comprising:

administering an anti-hypertensive drug;

administering inhaled nitric oxide; and

reducing symptoms of oxidative stress and/or fibrosis in a patient.

44 . The method of claim 41 , wherein the anti-fibrotic drug is an IPF drug.

45 . The method of claim 42 , wherein the calcium channel blocker is nifedipine.

46 . The method of claim 43 , wherein the anti-hypertensive drug is riociguat.

47 . A method of providing a therapeutic composition comprising:

administering a prostacyclin;

administering inhaled nitric oxide;

and allowing the nitric oxide to provide an additive effect to reduce symptoms of oxidative stress and/or fibrosis in a patient.

48 . A method of providing a therapeutic composition comprising:

administering a caspase regulator;

administering inhaled nitric oxide; and

modulating cellular apoptosis in a patient.

49 . A method for providing a therapeutic composition comprising:

identifying a mammal having or at risk of developing a haemolytic condition;

positioning a mammal for nitric oxide treatment;

administering exogenous nitric oxide; and

reducing symptoms of hemolysis in the mammal.

50 . The method of claim 50 , wherein the hemolysis resulted from venom.

51 . The method of claim 50 , wherein the venom is from a snake, scorpion, or sea anemone.

52 . The method of claim 50 , wherein the hemolysis resulted from a bacterial infection.

53 . The method of claim 50 , wherein the hemolysis is caused by proteolysis.

54 . A method of providing a therapeutic composition comprising:

identifying a mammal having or at risk of developing an ischemic condition;

administering exogenous nitric oxide; and

administering a drug with the nitric oxide to modulate remote ischemic conditioning pathway.

55 . The method of claim wherein exogenous NO is administered over approximately a 30 minute period at low dose effective to cause accumulation of hypoxia inducible factor(s) and PHDs to promote ROS signalling.

56 . The method of claim 54 , further comprising improving organ preservation by down regulating mitochondrial metabolic activity.

57 . The method of claim 55 , wherein modulating hypoxia inducible factor(s) causes erythropoietin production to stimulate red cell production.

58 . The method of claim 1 , further comprising modulating a platelet derived growth factor pathway to reduce symptoms of fibrosis in a patient.