Adenosine A2a Receptor Stimulation Attenuates Ischemia-Reperfusion Injury and Improves Survival in A Porcine Model of DCD Liver Transplantation

Autor: Thomas Minor, Rene Tolba, Georg Lurje, Shaowei Song, Zoltan Czigany, Eve Christiana Craigie, Yuzo Yamamoto, Kei Yonezawa
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Adenosine
Swine
medicine.medical_treatment
Medizin
Adenosine A2A receptor
Liver transplantation
Potassium Chloride
lcsh:Chemistry
chemistry.chemical_compound
0302 clinical medicine
Living Donors
Mannitol
Warm Ischemia
lcsh:QH301-705.5
Spectroscopy
liver transplantation
General Medicine
Organ Preservation
reperfusion injury
Computer Science Applications
surgical procedures
operative
Liver
030220 oncology & carcinogenesis
030211 gastroenterology & hepatology
Female
Agonist
medicine.medical_specialty
Adenosine A2 Receptor Agonists
Receptor
Adenosine A2A
medicine.drug_class
Organ Preservation Solutions
Urology
Ischemia
microcirculation
donation after circulatory death
survival
Catalysis
Article
Inorganic Chemistry
03 medical and health sciences
Phenethylamines
medicine
Animals
hepatoprotection
Physical and Theoretical Chemistry
Molecular Biology
porcine model
CGS-21680
business.industry
Organic Chemistry
medicine.disease
Adenosine receptor
Disease Models
Animal
Glucose
chemistry
lcsh:Biology (General)
lcsh:QD1-999
Liver function
adenosine A2a agonist
business
Reperfusion injury
Procaine
Zdroj: International Journal of Molecular Sciences
Volume 21
Issue 18
International journal of molecular sciences 21(18), 6747 (2020). doi:10.3390/ijms21186747 special issue: "Special Issue "New Frontiers in Organ Preservation and Hepatoprotection" / Special Issue Editor: Prof. Dr. René Hany Tolba, Guest Editor"
International Journal of Molecular Sciences, Vol 21, Iss 6747, p 6747 (2020)
ISSN: 1422-0067
DOI: 10.3390/ijms21186747
Popis: Orthotopic liver transplantation (OLT) using allografts from donation after circulatory death (DCD) is potentially associated with compromised clinical outcomes due to ischemia-reperfusion injury (IRI)-induced organ damage and graft-related complications. The aim of this study was to provide in vivo data on the effects of adenosine A2a receptor stimulation in a clinically relevant large animal model of DCD liver transplantation. Cardiac arrest was induced in German Landrace pigs (n = 10
20&ndash
25 kg). After 30 min of warm ischemia, the donor liver was retrieved following a cold flush with 3 L of histidine-tryptophan-ketoglutarate-HTK solution. Animals of the treatment group (n = 5/group) received a standard dose of the selective adenosine receptor agonist CGS 21680 added to the cold flush. All grafts were stored for 4.5 h at 4 °
C in HTK-solution before OLT. Hepatocellular injury, apoptosis, protein kinase A-PKA activity, graft microcirculation, liver function, and animal survival were assessed. Compared to untreated livers, adenosine A2a receptor stimulation resulted in improved tissue microcirculation (103% ±
5% vs. 38% ±
4% compared to baseline
p <
0.05), accelerated functional recovery of the graft (indocyanine green-plasma disappearance rate (ICG-PDR) of 75% ±
18% vs. 40% ±
30% after 3 h), increased PKA activity ratio (56% ±
3% vs. 32% ±
3%
0.001 after 1 h), and consequently reduced tissue necrosis and apoptosis. The potent protective effects were clinically manifested in significantly improved survival in the treatment group after 72 h (100% vs. 40%
p = 0.04). The ex vivo administration of adenosine A2a receptor agonist during the back-table flush mitigates IRI-mediated tissue damage and improves functional graft recovery and survival in a large animal model of DCD liver transplantation.
Databáze: OpenAIRE
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