Administration And Monitoring Of Nitric Oxide In Ex Vivo Fluids

Abstract

Described are systems and methods for monitoring administration of nitric oxide (NO) to ex vivo fluids. Examples of such fluids include blood in extracorporeal membrane oxygenation (ECMO) circuits or perfusion fluids used for preserving ex vivo organs prior to transplanting in a recipient. The systems and methods described herein provide for administering nitric oxide to the fluid, monitoring nitric oxide or a nitric oxide marker in the fluid, and adjusting the nitric oxide administration.

What is claimed is: 
     
         1 . A method of preserving a liver for transplant, the method comprising:
 persufflating a liver with a persufflation gas comprising nitric oxide (NO);   monitoring one or more persufflation parameters in (i) the liver and/or (ii) a preservation fluid used to store the liver during persufflation, wherein the one or more persufflation parameters is selected from the group consisting of NO, a NO marker, an indicator of tissue damage, and combinations thereof; and   adjusting the amount of NO provided to the liver by the persufflation gas based on the monitoring of the one or more persufflation parameters.   
     
     
         2 . The method of  claim 1 , wherein the concentration of NO in the persufflation gas is in the range from 0.1 ppm to 300 ppm. 
     
     
         3 . The method of  claim 1 , wherein the persufflation gas further comprises oxygen. 
     
     
         4 . The method of  claim 1 , wherein the one or more persufflation parameters is monitored continuously. 
     
     
         5 . The method of  claim 1 , further comprising perfusing the liver with a perfusion fluid comprising NO and/or a NO donor. 
     
     
         6 . The method of  claim 5 , further comprising:
 monitoring one or more perfusion parameters in (i) the liver and/or (ii) the perfusion fluid, wherein the one or more perfusion parameters is selected from the group consisting of NO, a NO marker, an indicator of tissue damage, and combinations thereof; and   adjusting the amount of NO and/or NO donor provided to the liver by the perfusion fluid based on the monitoring of the one or more perfusion parameters.   
     
     
         7 . The method of  claim 5 , wherein the liver is perfused with the perfusion fluid before the liver is persufflated with the persufflation gas. 
     
     
         8 . The method of  claim 5 , wherein the perfusion fluid comprises red blood cells. 
     
     
         9 . The method of  claim 8 , further comprising oxygenating the perfusion fluid before perfusing the liver. 
     
     
         10 . The method of  claim 6 , wherein adjusting one or more of (i) the amount of NO provided to the liver by the persufflation gas or (ii) the amount of NO provided to the liver by the perfusion fluid comprises:
 adjusting a NO concentration in a flow of gas delivered to the persufflation gas and/or perfusion fluid, and/or   adjusting a flow rate of the gas delivered to the persufflation gas and/or perfusion fluid.   
     
     
         11 . The method of  claim 1 , wherein monitoring the indicator of tissue damage comprises monitoring one or more of aspartate aminotransferase (AST) or alanine aminotransferase (ALT). 
     
     
         12 . The method of  claim 1 , wherein the viability of the liver is increased. 
     
     
         13 . A method of preserving a lung for transplant, the method comprising:
 perfusing a lung with a perfusion fluid comprising nitric oxide (NO) and/or a NO donor, and/or ventilating the lung with a ventilation gas comprising NO;   monitoring one or more parameters of the perfusion fluid and/or monitoring one or more parameters of the ventilation gas and/or monitoring one or more parameters of the lung,
 wherein the one or more parameters of the perfusion fluid is selected from the group consisting of NO, a NO marker, an indicator of tissue damage, and combinations thereof, 
 wherein the one or more parameters of the ventilation gas is selected from the group consisting of NO, NO 2 , and combinations thereof; and 
 wherein the one or more parameters of the lung is selected from the group consisting of NO, a NO marker, an indicator of tissue damage, a pulmonary parameter, and combinations thereof; and 
   adjusting one or more of (i) the amount of NO and/or NO donor provided to the lung by the perfusion fluid based on the monitoring of the one or more parameters of the perfusion fluid and/or the monitoring of the one or more parameters of the lung; or (ii) the amount of NO provided to the lung by the ventilation gas based on the monitoring of the one or more parameters of the ventilation gas and/or the monitoring of the one or more parameters of the lung.   
     
     
         14 . The method of  claim 13 , wherein the lung is perfused and ventilated simultaneously. 
     
     
         15 . The method of  claim 13 , wherein the perfusion fluid comprises red blood cells. 
     
     
         16 . The method of  claim 13 , wherein pulmonary vascular resistance is monitored and the amount of NO provided to the lung by the ventilation gas is adjusted based on the monitoring of pulmonary vascular resistance. 
     
     
         17 . The method of  claim 13 , wherein the one or more parameters is monitored continuously. 
     
     
         18 . The method of  claim 13 , wherein adjusting one or more of (i) the amount of NO provided to the lung by the perfusion fluid or (ii) the amount of NO provided to the lung by the ventilation gas comprises:
 adjusting a NO concentration in a flow of gas delivered to the perfusion fluid and/or ventilation gas, and/or   adjusting a flow rate of the gas delivered to the perfusion fluid and/or ventilation gas.   
     
     
         19 . The method of  claim 18 , wherein NO concentration in the gas delivered to the perfusion fluid and/or ventilation gas is in the range from 0.1 ppm to 300 ppm. 
     
     
         20 . The method of  claim 13 , wherein the viability of the lung is increased.