Perfusion Solution for Donor Organ Preservation
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Solution Overview
Problem
Current preservation methods for donor organs, particularly hearts from donation after cardiac death (DCD) donors, are limited in extending viability beyond 4 hours and fail to ensure consistent functional recovery post-transplantation due to challenges with warm ischemia and reperfusion injury.
Innovation Solution
A sterile aqueous perfusion solution with specific ion and buffer compositions, including sodium, potassium, magnesium, calcium, TRIS, bicarbonate, aspartate, glucose, insulin, adenosine, and reduced glutathione, oxygenated to 50-100% O2, is used to perfuse donor hearts, avoiding phosphate to prevent magnesium phosphate precipitation and promoting energy recovery and metabolic stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If hypothermic preservation is used to extend organ viability, then preservation time is prolonged, but functional recovery after transplantation is inconsistent
Solution Approach 1:
The patent modifies the chemical composition parameters of the preservation solution by incorporating specific concentrations of potassium (10-20 mM), magnesium (5-10 mM), calcium (0.2-1.0 mM), and buffers (TRIS, bicarbonate) to optimize cellular metabolism during preservation. This chemical parameter optimization enables prolonged preservation time while maintaining consistent functional recovery by creating a physiological environment that supports cellular viability throughout the preservation period.
Solution Approach 2:
The invention uses a composite preservation solution containing multiple complementary components: cardioplegic agents for cardiac arrest, buffers (TRIS and bicarbonate) for pH maintenance, energy substrates (glucose, aspartate), and antioxidants (reduced glutathione, adenosine). This composite formulation works synergistically to extend preservation time while ensuring reliable functional recovery by addressing multiple cellular needs simultaneously.
2Reliability
If warm perfusion is used to maintain physiological pressure and flow, then organ viability is improved, but device complexity and cost increase
Solution Approach 1:
The patent replaces complex mechanical perfusion systems with a chemically-based preservation solution that utilizes the organ's own vascular anatomy. The solution is perfused through the heart's natural coronary arteries and veins, eliminating the need for external heart-lung machines and complex mechanical perfusion devices. This substitution maintains organ viability through optimized chemical composition while dramatically reducing device complexity.
Solution Approach 2:
The invention introduces a chemically optimized preservation solution as an intermediary between the donor organ and the preservation process. This solution acts as a mediator that provides nutrients, removes waste products, and maintains cellular function without requiring complex mechanical intervention. The solution itself becomes the transport medium, simplifying the overall system by eliminating the need for external pumping and monitoring devices.
3Stability of the object's composition
If phosphate is included in the perfusion solution, then buffering capacity is improved, but magnesium phosphate precipitation occurs
Solution Approach 1:
The patent removes phosphate from the perfusion solution formulation to eliminate the harmful precipitation reaction between magnesium and phosphate. The buffering capacity is maintained through alternative buffers (TRIS and bicarbonate) that do not interact with magnesium to form precipitates. This extraction of the problematic component resolves the precipitation issue while preserving the essential buffering function through different chemical agents.
Solution Approach 2:
The invention replaces phosphate-based buffering with alternative buffer systems (TRIS and bicarbonate) that provide similar pH control functionality without the harmful side effect of magnesium precipitation. These alternative buffers serve as functional copies that achieve the same buffering objective through different chemical mechanisms, avoiding the incompatibility issue entirely.
4Ease of manufacture
If 4 hours cold ischemia limit is enforced, then organ preservation is simplified, but transplantation window is restricted
Solution Approach 1:
The patent optimizes the chemical composition parameters of the preservation solution to extend the functional preservation window beyond the traditional 4-hour limit. By incorporating specific concentrations of potassium, magnesium, calcium, and metabolic substrates, the solution maintains cellular viability for extended periods. This parameter optimization increases transplantation availability by providing a longer window for organ transport and matching while maintaining preservation simplicity through a single, chemically optimized formulation.
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
This solution prolongs donor organ preservation beyond standard limits, facilitates aerobic metabolism, enhances functional and metabolic recovery, and supports successful transplantation by reducing ischemic damage and reperfusion injury, while being simple and practical for clinical application.
Implementation Method 1
The solution is oxygenated using 50-100% O2
Implementation Method 2
TRIS (tris[hydorxymethyl]aminomethane hydrochloride) or a similar buffer, preferably 20 mM TRIS, between 10 and 30 mM sodium bicarbonate
Implementation Method 3
perfusion through the vascular bed of the organ with a buffered salt solution containing nutrients
Implementation Method 4
The osmolarity of the solution was 330 mOsm/L
Data Source
AI summary
The invention provides a perfusion stock composition, for preserving a donor organ for transplantation, comprising: a source of 60 to 100 mM Na+; a source of 10 to 20 mM K+; a source of 5 to 10 mM Mg2+; a source of 0.25 to 0.75 mM Ca 2+; 10 to 40 mM Tris(hydroxymethyl)aminomethane hydrochloride (Tris or THAM), 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES), 3-(N-morpholino)propanesulfonic acid (MOPS), 2-(N-mo:rpholino)ethanesulfonic acid (IviES), NjN-bis-(2-hy-droxyethyl)-2-aminoethansulfonic acid (BES), or N/-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid (TES); a source of 10 to 30 mM HC03−; 1 to 30 mM glucose; 1 to 20 U/L insulin; 1 to 10 mM fructose diphosphate or a salt thereof; 1 to 40 mM aspartate or glutamate; 1 to 10 mM adenosine, cAMP or cGMP; 1 to 10 mM reduced glutathione; and 30 to 100 mM lactobionate or mamlitol; and optionally a diluent. The invention also provides a perfusion composition, a kit, a method, and a perfusion apparatus, each related to the perfusion stock composition.