Nitric Oxide Administration for ECMO Circuit and Organ Preservation

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Solution Overview

Problem

Current methods for reducing ischemia-reperfusion injury and maintaining organ viability during transplantation are inadequate, and existing ECMO systems face issues with clogging due to platelet activation, leading to inefficiencies and tissue damage.

Innovation Solution

Administering nitric oxide (NO) to ex vivo fluids and monitoring its levels to adjust administration based on NO markers, such as methemoglobin, to prevent clogging in ECMO circuits and enhance organ preservation by reducing oxidative stress and microcirculation alterations.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Use of energy by moving object

If traditional oxygen perfusion is used to reduce ischemic damage, then oxygen supply is improved, but tissue damage increases due to reperfusion injury

Engineering Contradiction:

Improveoxygen supplyVSAvoidreperfusion injury

Core Design Contradiction:

Use of energy by moving objectVSObject-affected harmful factors

Solution Approach 1:

The patent applies preliminary action by administering nitric oxide to organs and tissues before reperfusion occurs. This pre-treatment creates a protective state that prevents reperfusion injury when oxygenated blood is restored, rather than waiting for the injury to occur and then treating it

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

Nitric oxide serves as an intermediary substance that mediates between the harmful reperfusion event and the tissue. It acts as a signaling molecule that triggers protective cellular responses, including activation of protective enzymes and reduction of oxidative stress, thereby protecting tissues from reperfusion injury

Inventive Principle:

Principle #24Intermediary (Mediator)

2Duration of action of moving object

If organs are preserved in cold physiologic fluid, then metabolic activity is reduced, but preservation duration is limited and success decreases with time

Engineering Contradiction:

Improvepreservation durationVSAvoidtransplant success

Core Design Contradiction:

Duration of action of moving objectVSReliability

Solution Approach 1:

The patent applies parameter changes by altering the chemical environment during preservation through nitric oxide administration. This changes the physiological state of preserved organs, activating protective pathways that extend viable preservation time beyond what cold storage alone can achieve

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The system employs feedback mechanisms by monitoring organ viability parameters during preservation and adjusting nitric oxide administration accordingly. This closed-loop approach ensures optimal protective effects are maintained throughout the preservation period

Inventive Principle:

Principle #23Feedback

3Quantity of substance

If ECMO systems use filters to remove blood clots, then blood purification is improved, but circuit clogging occurs due to platelet activation

Engineering Contradiction:

Improveblood purificationVSAvoidplatelet activation

Core Design Contradiction:

Quantity of substanceVSObject-generated harmful factors

Solution Approach 1:

The patent converts the harmful effect of platelet activation into a beneficial outcome by using the activated platelets as a delivery mechanism. Nitric oxide causes platelet activation that triggers release of protective factors and prevents further thrombus formation, transforming the potentially harmful activation into a protective response

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The system changes the chemical parameters of blood in the ECMO circuit by introducing nitric oxide. This alters platelet behavior and coagulation parameters, preventing the cascade that leads to circuit clogging while maintaining necessary filtration functions

Inventive Principle:

Principle #35Parameter changes

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The NO administration method effectively reduces platelet activation, extends ECMO circuit life, and improves organ viability by minimizing ischemia-reperfusion injury and microcirculation alterations, thereby enhancing the success of organ transplants.

Implementation Method 1

it is expected that NO administration to blood in an ECMO circuit will reduce platelet activation in the blood, and thus help prevent clogging in the ECMO circuit

Methodology Applied

Scientific EffectPlatelet activation inhibition:

Implementation Method 2

enhance organ preservation by reducing oxidative stress and microcirculation alterations

Methodology Applied

Scientific EffectOxidative stress reduction: Oxidation

Implementation Method 3

monitoring NO and/or a NO marker (e.g., methemoglobin) in the ex vivo fluid

Methodology Applied

Scientific EffectMethemoglobin formation: Oxidation

Data Source

PatentUS12052987B2Administration and monitoring of nitric oxide in ex vivo fluids

Publication Date: 2024.08.06 MALLINCKRODT PHARMACEUTICALS IRELAND LTD

AI summary

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.