Hydrogen sulfide (H2S) reduces oxygen and ATP consumption in the isolated perfused pig kidney

Autor:	Alban Longchamp, J Songeon, Raphael P. H. Meier, Leo Buhler, Antonio Nastasi, Jean-Marc Corpataux, Antoine Klauser, Florent Allagnat, François Lazeyras, T Agius, R Ruttiman
Rok vydání:	2021
Předmět:	Kidney Chromatography business.industry Hydrogen sulfide chemistry.chemical_element Metabolism medicine.disease Oxygen Transplantation chemistry.chemical_compound medicine.anatomical_structure chemistry Medicine Surgery Organ donation business Reperfusion injury Perfusion
Zdroj:	British Journal of Surgery. 108
ISSN:	1365-2168 0007-1323
DOI:	10.1093/bjs/znab202.082
Popis:	Objective Organ donation after circulatory death [DCD] has the potential to reduce the shortage of kidneys available for transplantation. However, many DCD grafts are discarded because of long warm ischemia times. Strategies reducing oxygen demand may minimize damages caused by ischemia/reperfusion injury. Ex-vivo, Hydrogen sulfide (H2S) reduces oxygen and ATP consumption of the isolated perfused kidney, reduces inflammation and improves renal function following ischemia reperfusion injury in rodents. However, the benefits and applicability of H2S in clinically relevant model remain unknown. Methods To mimic DCD, pig kidneys underwent 0 or 60 min of warm ischemia, before oxygenated hypothermic machine perfusion (HMP). NaHS (100µM), an H2S donor, was added to the perfusion media or injected as an intra-arterial bolus before warm ischemia. After 2 hours of HMP, kidneys were transplanted and reperfused for 1 hour before harvest. Kidney function was assesses before, after and during ex vivo perfusion by measuring energy metabolites, Gadolinium elimination by pMRI and histopathological scoring. Results Warm ischemia (60 min) induced significant histological damages, delayed cortical and medullary Gadolinium elimination (perfusion), and reduced ATP levels, but not its precursors (AMP). As expected, ATP levels and kidney perfusion both inversely correlated with the severity of kidney histological injury. NaHS reduced metabolism during warm ischemia, and seemed to increase kidney ATP levels and viability after reperfusion. Conclusion Our preliminary data suggest that the H2S donor NaHS reduces kidney metabolism and protects from warm ischemia. Further experiments will identify the best administration protocol and the clinical relevance of H2S supplementation in the context of organ preservation.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::9eca44ecc6ce92a0941d2900e40ba8d3 https://doi.org/10.1093/bjs/znab202.082 Zobrazit plný text záznamu