Hydrogen sulphide-induced hypometabolism in human-sized porcine kidneys

Autor: Leonie H Venema, Koen D. W. Hendriks, Sijbrand Hofker, Harry van Goor, Hanno Maassen, Henri G. D. Leuvenink, Robert H. Henning, Annemieke M Coester
Přispěvatelé: Groningen Kidney Center (GKC), Groningen Institute for Organ Transplantation (GIOT)
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Physiology
Swine
ISCHEMIA-REPERFUSION INJURY
030230 surgery
Kidney
Kidney Function Tests
Biochemistry
Vascular Medicine
PROTECTS
chemistry.chemical_compound
0302 clinical medicine
Ischemia
Medicine and Health Sciences
Renal Transplantation
Hydrogen Sulfide
GASOTRANSMITTERS
Energy-Producing Organelles
Multidisciplinary
H2S
Respiration
Organ Size
RECOVERY
Mitochondria
APOPTOSIS
Creatinine
Medicine
Anatomy
Cellular Structures and Organelles
VASORELAXANT
Perfusion
Research Article
medicine.medical_specialty
Histology
Fractional excretion of sodium
Science
Renal function
Surgical and Invasive Medical Procedures
Bioenergetics
Urinary System Procedures
03 medical and health sciences
Oxygen Consumption
Internal medicine
medicine
Animals
Humans
PRESERVATION
Machine perfusion
NITRIC-OXIDE
TRANSPLANTATION
Biology and Life Sciences
Kidney metabolism
Kidneys
Renal System
Cell Biology
Organ Transplantation
medicine.disease
Transplantation
030104 developmental biology
Endocrinology
chemistry
Physiological Processes
Energy Metabolism
Biomarkers
Zdroj: PLoS ONE, Vol 14, Iss 11, p e0225152 (2019)
PLoS ONE, 14(11):0225152. PUBLIC LIBRARY SCIENCE
PLoS ONE
ISSN: 1932-6203
Popis: BackgroundSince 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.MethodsPorcine 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.ResultsHydrogen 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.ConclusionIn 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.
Databáze: OpenAIRE
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