Cardiac Preservation Solution Mitigating Ischemic Necrosis

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Solution Overview

Problem

Current solutions for preserving cardiac grafts are limited to a short duration of 4 to 6 hours, necessitating the development of a method to extend preservation time while maintaining organ viability for transplantation.

Innovation Solution

An aqueous solution containing 100 mM to 130 mM of Na+, 12 mM to 15 mM of K+, 0.25 mM to 1.3 mM of Ca++, 0.25 μM to 1.5 μM of cyclosporin A, and 0.25 μM to 1.5 μM of taxol, which acts synergistically to inhibit mitochondrial pore transition permeability and stabilize cellular microtubules, thereby enhancing cardioprotection during hypothermic ischemia.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of moving object

If conventional preservation solutions are used, then the organ can be preserved for 4-6 hours, but the preservation duration is too short for extended transplantation logistics

Engineering Contradiction:

Improvepreservation durationVSAvoidorgan viability

Core Design Contradiction:

Duration of action of moving objectVSReliability

Solution Approach 1:

The preservation solution combines multiple protective agents (cyclosporin A and taxol) with electrolytes and metabolic substrates to create a composite formulation that addresses multiple preservation mechanisms simultaneously, extending viable preservation time while maintaining organ functionality

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The solution modifies chemical parameters by incorporating specific concentrations of cyclosporin A (0.25-1.5 μM) and taxol (0.25-1.5 μM) to alter the preservation mechanism, enabling extended duration without compromising viability through synergistic pharmacological action

Inventive Principle:

Principle #35Parameter changes

2Duration of action of moving object

If preservation time is extended, then transplantation logistics are improved, but tissue damage increases

Engineering Contradiction:

Improvepreservation durationVSAvoidtissue damage

Core Design Contradiction:

Duration of action of moving objectVSObject-affected harmful factors

Solution Approach 1:

The solution applies preliminary protective action by incorporating cyclosporin A and taxol before ischemic damage occurs, preventing mitochondrial pore transition and stabilizing microtubules in advance to counteract the harmful effects of extended ischemia

Inventive Principle:

Principle #9Preliminary anti-action

Solution Approach 2:

The formulation provides beforehand cushioning against ischemic damage through the synergistic action of cyclosporin A and taxol, which protect cellular structures and metabolic pathways before irreversible damage can occur during extended preservation

Inventive Principle:

Principle #11Beforehand cushioning (Prior cushioning)

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 solution effectively prolongs the preservation duration of cardiac organs by maintaining viability and reducing tissue damage during cold ischemia, with cyclosporin A and taxol at optimal concentrations of 1 μM each, demonstrating improved cardiomyocyte survival and reduced necrosis in both cell and whole heart models.

Implementation Method 1

cyclosporin A and taxol, which acts synergistically to inhibit mitochondrial pore transition permeability

Methodology Applied

Scientific EffectMitochondrial pore transition inhibition:

Implementation Method 2

cyclosporin A and taxol, which acts synergistically to inhibit mitochondrial pore transition permeability and stabilize cellular microtubules

Methodology Applied

Scientific EffectMicrotubule stabilization:

Data Source

PatentUS10440947B2Aqueous solution for preserving an organ and uses during hypothermic ischemia

Publication Date: 2019.10.15 INST NAT DE LA SANTE & DE LA RECHERCHE MEDICALE (INSERM)

AI summary

The present invention relates to an aqueous solution for organ preservation, in particular for the myocardium, the solution comprising:100 mM to 130 mM of Na+;12 mM to 15 mM of K+;0.25 mM to 1.3 mM of Ca++;0.5 μM to 1.5 μM of cyclosporin A; and0.5 μM to 1.5 μM of taxol,and it also relates to the joint use of cyclosporin A and taxol in a solution for in vitro preservation of an organ, in particular the myocardium.