Methods of administering nitric oxide to arterial or arterialized blood

Abstract

The present invention provides methods of administering nitric oxide (NO) to a patient, the method comprising delivering nitric oxide-containing gas directly into arterial or arterialized blood. The methods of the present invention may be used in the treatment or prevention of a variety of diseases and disorders responsive to nitric oxide, including those resulting from ischemia or hypoxia.

What is claimed is: 
     
         1 . A method of treating a disease, disorder or condition responsive to nitric oxide in a patient in need thereof, comprising:
 oxygenating withdrawn blood through an oxygen permeable membrane of an oxygen transfer unit within an oxygenation compartment of an extracorporeal membrane oxygenation system (ECMO) to produce arterialized blood;   administering a therapeutically effective amount of nitric oxide (NO)-containing gas directly into the oxygenated blood of the patient through an NO permeable membrane of an NO transfer unit of a gas transfer unit downstream of the oxygen transfer unit; and   infusing the blood produced in step b) into the patient.   
     
     
         2 . The method of  claim 1 , wherein the blood is infused into the patient via an arterial cannula. 
     
     
         3 . The method of  claim 1 , wherein any remaining oxygen is removed from the oxygen transfer unit though an oxygen venting device and any remaining NO is removed from the NO transfer unit through an NO venting device. 
     
     
         4 . The method of  claim 1 , wherein the administration is a bolus administration of the nitric oxide-containing gas. 
     
     
         5 . The method of  claim 1 , wherein a delivery concentration of nitric oxide-containing gas is in a range of 0.1-500 ppm. 
     
     
         6 . The method of  claim 1 , wherein the administration is a continuous administration. 
     
     
         7 . The method of  claim 1 , wherein the treated disease, disorder or condition is ischemia or hypoxia. 
     
     
         8 . The method of  claim 1  wherein the nitric oxide-containing gas is administered before onset of the disease, disorder or condition. 
     
     
         9 . The method of  claim 1  wherein the nitric oxide-containing gas is administered after onset of the disease, disorder or condition. 
     
     
         10 . The method of  claim 1 , wherein the NO transfer unit is inside the oxygenation compartment. 
     
     
         11 . The method of  claim 1 , wherein the NO transfer unit is outside the oxygenation compartment. 
     
     
         12 . The method of  claim 1  further comprising:
 introducing the oxygen into the oxygen transfer unit from an oxygen source in fluid communication with the oxygen transfer unit through an inlet in the oxygen transfer unit; and 
 introducing the NO into the NO transfer unit from a NO delivery device in fluid communication with the NO transfer unit through an inlet in the NO transfer unit. 
 
     
     
         13 . The method of  claim 12  further comprising generating and/or storing NO in a NO generator/reservoir connected to the NO delivery device. 
     
     
         14 . An extracorporeal membrane oxygenation (ECMO) system comprising:
 a chamber, wherein blood enters an oxygenation compartment though an inlet in the chamber;   an oxygen transfer unit having an oxygen permeable membrane, wherein the oxygen transfer unit is within the oxygenation compartment; and   a nitric oxide (NO) transfer unit having an NO permeable membrane,   wherein the oxygen transfer unit is separated from an upstream portion of the chamber by the oxygen permeable membrane which exchanges oxygen for carbon dioxide in the blood to produce arterialized blood, and the NO transfer unit is separated from a downstream portion of the chamber by the NO permeable membrane which exchanges NO for oxygen in the arterialized blood.   
     
     
         15 . The ECMO system of  claim 14  further comprising an oxygen venting device in fluid communication with the oxygen transfer unit through an outlet of the oxygen transfer unit operable to receive any remaining oxygen and an NO venting device in fluid communication with the NO transfer unit through the outlet of the NO transfer unit operable to receive any remaining NO. 
     
     
         16 . The ECMO system of  claim 14 , wherein the NO transfer unit is inside the oxygenation compartment. 
     
     
         17 . The ECMO system of  claim 14 , wherein the NO transfer unit is outside the oxygenation compartment. 
     
     
         18 . The ECMO system of  claim 14  further comprising:
 an oxygen source in fluid communication with the oxygen transfer unit through an inlet in the oxygen transfer unit; and 
 an NO delivery device in fluid communication with the NO transfer unit through an inlet in the NO transfer unit. 
 
     
     
         19 . The ECMO system of  claim 18  further comprising a NO generator/reservoir connected to the NO delivery device for generating and/or holding the NO. 
     
     
         20 . The ECMO system of  claim 18 , wherein the NO delivery device is a metering device, an injector or a pump.