Hydrogen sulphide-induced hypometabolism in human-sized porcine kidneys

English version

Autoři: Hanno Maassen ^aff001; Koen D. W. Hendriks ^aff001; Leonie H. Venema ^aff001; Rob H. Henning ^aff003; Sijbrand H. Hofker ^aff001; Harry van Goor ^aff002; Henri G. D. Leuvenink ^aff001; Annemieke M. Coester ^aff001
Působiště autorů: Department of Surgery, UMCG, University of Groningen, Groningen, the Netherlands ^aff001; Department of Pathology and Medical Biology, UMCG, University of Groningen, Groningen, the Netherlands ^aff002; Department of Clinical Pharmacy and Pharmacology, UMCG, University of Groningen, Groningen, the Netherlands ^aff003
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0225152

Souhrn

Background

Since the start of organ transplantation, hypothermia-forced hypometabolism has been the cornerstone in organ preservation. Cold preservation showed to protect against ischemia, although post-transplant injury still occurs and further improvement in preservation techniques is needed. We hypothesize that hydrogen sulphide can be used as such a new preservation method, by inducing a reversible hypometabolic state in human sized kidneys during normothermic machine perfusion.

Methods

Porcine kidneys were connected to an ex-vivo isolated, oxygen supplemented, normothermic blood perfusion set-up. Experimental kidneys (n = 5) received a 85mg NaHS infusion of 100 ppm and were compared to controls (n = 5). As a reflection of the cellular metabolism, oxygen consumption, mitochondrial activity and tissue ATP levels were measured. Kidney function was assessed by creatinine clearance and fractional excretion of sodium. To rule out potential structural and functional deterioration, kidneys were studied for biochemical markers and histology.

Results

Hydrogen sulphide strongly decreased oxygen consumption by 61%, which was associated with a marked decrease in mitochondrial activity/function, without directly affecting ATP levels. Renal biological markers, renal function and histology did not change after hydrogen sulphide treatment.

Conclusion

In conclusion, we showed that hydrogen sulphide can induce a controllable hypometabolic state in a human sized organ, without damaging the organ itself and could thereby be a promising therapeutic alternative for cold preservation under normothermic conditions in renal transplantation.

Klíčová slova:

Mitochondria – Renal system – Kidneys – Ischemia – Renal transplantation – Creatinine – Histology – Oxygen consumption

Zdroje

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