Hypothermic Oxygenated Perfusion Solution with Carbon Monoxide-Releasing Molecules
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Solution Overview
Problem
Current hypothermic oxygenated perfusion solutions are ineffective in repairing kidneys from donation after circulatory death donors due to inadequate vascular regulation and uneven perfusion, leading to increased discard rates and complications in transplantation.
Innovation Solution
A hypothermic oxygenated perfusion solution containing carbon monoxide-releasing molecules, such as carbon monoxide-releasing molecules-2, -3, or -401, is used to regulate vascular function and improve perfusion, reducing ischemia-reperfusion injury and promoting even distribution of oxygen and carbon monoxide within the kidney.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If traditional static cold storage is used for kidney preservation, then the preservation process is simple and easy to operate, but the kidney quality deteriorates due to ischemia/hypoxia and the discard rate increases
Solution Approach 1:
The patent replaces the traditional static cold storage mechanical system with a dynamic hypothermic oxygenated perfusion system. This system uses a perfusion pump to deliver oxygenated preservation solution at controlled flow rates (10-50 mL/min), maintaining kidney tissue oxygenation and metabolism while preserving the organ ex vivo. The perfusion system transforms the static preservation environment into a dynamic physiological-like environment, improving kidney quality without significantly increasing operational complexity.
2Reliability
If hypothermic oxygenated perfusion technology is applied to kidneys from donation after circulatory death donors, then the repair effect is limited for uncontrollable donors, but the technology complexity increases
Solution Approach 1:
The patent optimizes key perfusion parameters including temperature (4-10°C hypothermia), flow rate (10-50 mL/min), and oxygenation levels to enhance the repair effect for kidneys from donation after circulatory death donors. The preservation solution contains specific concentrations of antioxidants (vitamin C 1-10 mM, vitamin E 0.1-1 mM) and anti-inflammatory agents to counteract reperfusion injury. These parameter optimizations improve repair efficacy without requiring fundamental changes to the perfusion system architecture.
Solution Approach 2:
The patent introduces carbon monoxide-releasing molecules (such as CORM-2, CORM-3, or CORM-401) as intermediary substances in the preservation solution. These molecules provide controlled CO release (10-100 μM concentration) during perfusion, which acts as a signaling molecule to reduce intrarenal resistance, promote vasodilation, and enhance microcirculatory perfusion. This intermediary approach improves repair effects for uncontrollable donors by modulating vascular tone and reducing ischemia-reperfusion injury without requiring complex additional equipment.
3Quantity of substance
If the number of donor organs is expanded to meet transplantation demand, then the organ supply increases, but the discard rate of low-quality kidneys increases due to insufficient preservation technology
Solution Approach 1:
The patent applies hypothermic oxygenated perfusion immediately after kidney retrieval from donation after circulatory death donors, before the kidneys undergo irreversible damage. The perfusion process begins within minutes of organ retrieval and continues for 2-6 hours, performing preliminary repair of ischemic damage, clearing metabolic waste, and restoring microcirculatory function before transplantation. This preliminary action prevents quality deterioration and enables use of kidneys that would otherwise be discarded.
Solution Approach 2:
The patent implements continuous hypothermic oxygenated perfusion throughout the preservation period, maintaining constant oxygen delivery, nutrient supply, and waste removal. The perfusion system operates continuously with real-time monitoring of flow rate, pressure, and temperature, ensuring uninterrupted protective action on the kidney tissue. This continuous useful action prevents quality loss during the extended preservation period required for expanded donor organ utilization.
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 reduces intrarenal resistance, improves perfusion parameters, and enhances kidney quality by promoting vasodilation and reducing oxidative stress, thereby increasing the viability of kidneys for transplantation.
Implementation Method 1
The solution effectively reduces intrarenal resistance, improves perfusion parameters, and enhances kidney quality by promoting vasodilation
Implementation Method 2
The hypothermic oxygenated perfusion technology can effectively realize dynamic preservation of organs ex-vivo at a low temperature while maintaining certain energy metabolism, and alleviate mitochondrial energy metabolism disorder and the generation of a large amount of reactive oxygen species caused by ischemia/hypoxia
Implementation Method 3
The ischemia/hypoxia of organs causes anaerobic metabolism and acidosis of cells, thereby promoting the injury and the death of renal tubular epithelial cells and vascular endothelial cells
Data Source
AI summary
A hypothermic oxygenated perfusion solution for repairing kidney injury and use thereof belongs to the technical field of medical treatment. The hypothermic oxygenated perfusion solution is an organ preservation solution carrying carbon monoxide-releasing molecules. The hypothermic oxygenated perfusion solution can significantly increase the perfusion flow of the kidney, reduce the intrarenal resistance and significantly improve the histopathological integrality. The hypothermic oxygenated perfusion solution is provided for specifically repairing the kidney from donation after circulatory death donors, and has a huge application prospect for clinical transformation.