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Updated: Jan 10, 2026
Innovative Strategies for Organ Preservation in Heart Transplantation: Uniform Cooling Preservation and Ex-situ Normothermic Perfusion
Published on: November 28, 2025
Extended Preservation of Heart Grafts: LYPS Solution Maintains Cardiac Function During 20-Hour Static Cold Storage
Marie Védère1, Evan Faure1, Christophe Chouabe1
1CARMEN Laboratory, INSERM, INRAE, Université Claude Bernard Lyon 1, University of Lyon, 69500 Lyon, France.
Insights
A new heart preservation solution, LYPS (Lyon Preservation Solution), significantly improves graft viability by protecting against ischemia-reperfusion injury and enhancing mitochondrial function, offering better outcomes for heart transplantation.
Area of Science:
- Cardiology
- Transplantation Immunology
- Biochemistry
Background:
- Heart transplantation success is limited by donor organ shortages and damage from ischemia-reperfusion injury.
- Current preservation solutions inadequately maintain myocardial viability, impacting post-transplant function.
- Standardized strategies are needed to improve donor heart preservation.
Purpose of the Study:
- To evaluate an improved preservation solution, LYPS (Lyon Preservation Solution), for its efficacy in protecting myocardial grafts.
- To compare LYPS against established solutions (Celsior, St. Thomas) in preserving heart function and viability.
- To investigate LYPS's effects on mitochondrial function and electrophysiology during cold storage and reperfusion.
Main Methods:
- In vitro assessment of extracellular solutions on cardiac cell lines (H9C2) under simulated ischemia-reperfusion.
- Ex vivo evaluation of LYPS, Celsior, and St. Thomas solutions in isolated pig hearts subjected to cold static storage.
- Assessment of heart function, mitochondrial viability, and cardiomyocyte electrophysiology post-preservation.
Main Results:
- LYPS demonstrated superior protection against cell death and mitochondrial membrane potential loss compared to Celsior and St. Thomas solutions.
- LYPS outperformed St. Thomas in preserving mitochondrial function and limiting troponin I release.
- LYPS-treated hearts exhibited improved functional recovery, contractility, and rhythmicity upon reperfusion.
Conclusions:
- LYPS effectively preserves myocardial viability and function during long-term cold storage, outperforming current standards.
- The solution shows promise for enhancing donor heart quality and improving heart transplantation outcomes.
- Potential mechanisms involve modulation of the repolarizing IK1 current and mitochondrial metabolic activation.
Abstract:
Heart transplantation is severely limited by the shortage of suitable donor grafts, partly due to myocardial vulnerability to ischemia-reperfusion injury and the lack of standardized preservation strategies. Current solutions only partially maintain myocardial viability, compromising post-transplant function. To address this issue, we made further improvements to our preservation solution, LYPS (Lyon Preservation Solution), based on mitochondrial metabolic activation and the limitation of membrane depolarization. We first evaluated commonly used extracellular solutions (Celsior and St. Thomas (ST)) on cardiac cell lines (H9C2) exposed to 20 h of cold (4 °C) simulated ischemia followed by 2 h of simulated reperfusion. In parallel, the same three solutions were compared in isolated pig hearts subjected to 20 h of cold static storage followed by reperfusion, with a group directly reperfused with blood at 37 °C serving as the control. Heart function was assessed using a non-working heart preparation, while mitochondrial functions and electrophysiological analysis were evaluated via biopsies and isolated cardiomyocytes. LYPS provided superior protection against cell death and mitochondrial membrane potential loss in vitro, outperformed ST in preserving mitochondrial function, and limited troponin I release by the heart. During reperfusion, LYPS-treated hearts showed improved functional recovery and contractility and better rhythmicity with almost no defibrillation requirements. These effects may involve the modulation of the repolarizing IK1 current. Overall, LYPS effectively preserves myocardial viability and function, representing a promising strategy to enhance graft quality during long-term cold preservation, even through using cold static storage.
