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Subnormothermic isolated organ perfusion with Nicorandil increased cold ischemic tolerance of liver in experimental model.
- Source :
- Clinical Hemorheology & Microcirculation; 2022, Vol. 81 Issue 1, p1-12, 12p
- Publication Year :
- 2022
-
Abstract
- BACKGROUND: The cold ischemia –reperfusion injury may lead to microcirculatory disturbances, hepatocellular swelling, inflammation, and organ dysfunction. Nicorandil is an anti-ischemic, ATP-sensitive potassium (KATP) channel opener drug and has proved its effectiveness against hepatic Ischemia/Reperfusion (I/R) injury. OBJECTIVE: This study aimed to investigate the effect of Nicorandil on mitochondrial apoptosis, oxidative stress, inflammation, histopathological changes, and cold ischemic tolerance of the liver in an ex vivo experimental isolated-organ-perfusion model. METHODS: We used an ex vivo isolated rat liver perfusion system for this study. The grafts were retrieved from male Wistar rats (n = 5 in each), preserved in cold storage (CS) for 2 or 4 hours (group 1, 2), or perfused for 2 or 4 hours (group 3, 4) immediately after removal with Krebs Henseleit Buffer (KHB) solution or Nicorandil containing KHB solution under subnormothermic (22–25°C) conditions (group 5, 6). After 15 minutes incubation at room temperature, the livers were reperfused with acellular, oxygenated solution under normothermic condition for 60 minutes. RESULTS: In the Nicorandil perfused groups, significantly decreased liver enzymes, GLDH, TNF-alpha, and IL-1ß were measured from the perfusate. Antioxidant enzymactivity was higher in the perfused groups. Histopathological examination showed ameliorated tissue deterioration, preserved parenchymal structure, decreased apoptosis, and increased Bcl-2 activity in the Nicorandil perfused groups. CONCLUSIONS: Perfusion with Nicorandil containing KHB solution may increase cold ischemic tolerance of the liver via mitochondrial protection which can be a potential therapeutic target to improve graft survival during transplantation. [ABSTRACT FROM AUTHOR]
- Subjects :
- PERFUSION
LIVER
LIVER enzymes
COLD storage
LABORATORY rats
Subjects
Details
- Language :
- English
- ISSN :
- 13860291
- Volume :
- 81
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Clinical Hemorheology & Microcirculation
- Publication Type :
- Academic Journal
- Accession number :
- 156742545
- Full Text :
- https://doi.org/10.3233/CH-211263