Impact of storage temperature on the development of different cell death pathways and cardiac functions

• Published in: Archives of cardiovascular diseases 2024-06, Vol.117 (6-7), p.S179-S180
• Main Authors: Védère, Marie, Charouit, Yanis, Faure, Evan, Lo Grasso, Megane, Ferrera, Rene, Baetz, Delphine
• Format: Article
• Language: English
• ISSN: 1875-2136; 1875-2128
• DOI: 10.1016/j.acvd.2024.05.038

The world of heart transplantation is cruelly impacted by a shortage of grafts. This can be explained by the poor quality of preservation of heart grafts before transplantation and the absence of consensus in the solutions used worldwide. We developed a new original preservation solution named LYPS (for LYon Preservative Solution). Our objective was to compare LYPS to clinical solutions and to determine the impact of temperature on cell death pathways and their impact on heart functional recovery. We used a mimetic cold-ischemia-reperfusion H9C2 cellular model (20h preservation at 5-10-15-20 and 25°C, followed by 2h of reoxygenation at 37°C). Cell necrosis, apoptosis, and mitochondrial membrane potential were evaluated by flow cytometry. In parallel, an ex vivo retrograde perfusion rat heart model was used. Hearts were submitted to static preservation in LYPS, Celsior or Plegisol at 4°C and 15°C, then reperfused for 1h where cardiac functions are assessed. A preservation time kinetic was carried out to determine the maximum time at which the rat heart could be resuscitated to regain function (4-8-12-16-20h). In vitro results showed that, after 20h of cold hypothermia (5°C) preservation and 2h of reoxygenation, necrosis (2.8% LYPS vs. 79.3%, Plegisol, 61.6%, Celsior and 90% UW, respectively) and apoptosis were significantly reduced in LYPS comparing to other solutions. LYPS was effective in preserving DyM (85% in LYPS vs. 5% in other solutions). Moreover, mid-thermie seemed to be associated with less cell death with all solutions used (for ex: 90% at 4°C vs. 31% at 20°C in Plegisol). Preliminary ex vivo results show that, for short storage times (4h), there is no significant difference impact of the solution used on the cardiac functions but when the storage time is extended to 8 or 12hours, storage in LYPS seems to ensure a better functional recovery in comparison with Plegisol solution. Our preliminary data show that LYPS offers a cellular protection that allow a good preservation of cells during 20h where commercial solutions failed. Moreover, LYPS seems to offer better functional protection in ex vivo model, when preservation time is extended.