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Etude des biomarqueurs tissulaires et endothéliaux et profil métabolomique du greffon cardiaque en condition de perfusion ex vivo hypothermique

Year: 2025
Type: dissertation
Abstract: Ex situ hypothermic oxygenated perfusion (HOPE) prior to transplantation is a promising technique for cardiac graft (CG) preservation. However, the assessment of CG viability during HOPE is not routinely performed in clinical practice. The aim of this study was to investigate the endothelial and myocardial biomarkers evolution during hypothermic preservation.Materials and Methods:Eighteen pigs were divided into three groups: BH (“beating heart”, standard cardiac procurement using cardioplegia followed by 4-hour HOPE of the CGs with preservation solution, n=6), SCS (“static cold storage”, standard cardiac procurement using cardioplegia followed by 4-hour static preservation of the CGs in preservation solution, n=6), and DCD (“controlled circulatory death”, cardiac procurement following a DCD procedure followed by 4-hour HOPE of the CGs with preservation solution, n=6). Myocardial and endothelial biomarkers dissolved in the perfusate were quantified during hypothermic preservation. Metabolomic analyses were performed on perfusate samples collected at 0, 60, 120, and 240 minutes. The CGs were subsequently reperfused using a normothermic ex situ perfusion system (NESP) and transitioned to the working mode to assess hemodynamic performance.Results:The profiles of myocardial and endothelial biomarkers during the hypothermic preservation were similar among the three groups, except for lactate, which was significantly higher in the DCD group (p<0.0001). Despite a significantly more severe initial metabolic profile in DCD hearts compared with BH and SCS groups, metabolic recovery was observed during HOPE, except for lactate. Metabolomic analysis revealed a similar temporal evolution between 60 and 240 minutes across all groups, whereas the DCD metabolic profile at baseline differed from that of the BH and SCS groups. During NESP, myocardial lactate extraction (MLE; arterial lactate - venous lactate) was not correlated with the initial myocardial performance of the CGs (r=0.39, p=0.009). The cardiac index was significantly higher in the BH group compared with SCS and DCD groups (p=0.012).Conclusion:HOPE perfusion enables metabolic recovery of DCD hearts. MLE is not correlated with functional recovery of the hearts during NESP perfusion in working mode.
Language: English
Subfield: Surgery
Field: Medicine
Open Access status: green
OpenAlex ID: W7128749139
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