Administration and monitoring of nitric oxide in ex vivo fluids

Inventors

Potenziano, Jim • Hansell, Douglas R. • Griebel, Jeff • Costa, Eddie • Cooper, Lisa • Newman, David William

Assignees

Mallinckrodt Pharmaceuticals Ireland Ltd

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.

Core Innovation

The invention provides systems and methods for delivering nitric oxide (NO) to ex vivo fluids used in extracorporeal membrane oxygenation (ECMO) blood and in organ preservation contexts, including organ perfusion and persufflation, and fluids used during ventilation. The disclosure includes delivering NO to the ex vivo fluid while enabling monitoring and control of NO-related parameters and other clinical or chemical parameters relevant to organ preservation.

A primary embodiment is a method of preserving an ex vivo liver for transplant by persufflating the liver with a persufflation gas comprising nitric oxide (NO). The method monitors one or more persufflation parameters in the liver and/or in a preservation fluid used to store the liver during persufflation, where the one or more persufflation parameters includes an indicator of tissue damage.

The disclosed control strategy adjusts the amount of NO provided to the liver by the persufflation gas based on the monitoring of the one or more persufflation parameters. In particular, the indicator of tissue damage includes aspartate aminotransferase (AST), alanine aminotransferase (ALT), or combinations thereof, and dependent aspects further relate to monitoring NO markers such as methemoglobin and adjusting NO delivery based on NO concentration and/or gas flow rate.

Claims Coverage

The document provides one independent claim centered on NO-containing persufflation for ex vivo liver preservation, with additional features that refine monitoring and adjustment. The inventive features focus on monitoring tissue-damage indicators and adjusting NO delivery based on the monitored parameters.

Overall, the claim coverage requires NO-containing persufflation of an ex vivo liver for transplant, monitoring persufflation parameters in the liver and/or preservation fluid, and adjusting the delivered NO amount based on those monitored parameters. The monitored tissue-damage indicator is specified to include AST and/or ALT, with dependent features further specifying monitoring of methemoglobin and control via NO concentration and/or gas flow rate.

Stated Advantages

Documented Applications