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Human Atrial Natriuretic Peptide in Cold Storage of Donation After Circulatory Death Rat Livers: An Old but New Agent for Protecting Vascular Endothelia?
- Source :
-
Transplantation [Transplantation] 2019 Mar; Vol. 103 (3), pp. 512-521. - Publication Year :
- 2019
-
Abstract
- Background: Current critical shortage of donor organs has increased the use of donation after circulatory death (DCD) livers for transplantation, despite higher risk for primary nonfunction or ischemic cholangiopathy. Human atrial natriuretic peptide (hANP) is a cardiovascular hormone that possesses protective action to vascular endothelia. We aimed to clarify the therapeutic potential of hANP in cold storage of DCD livers.<br />Methods: Male Wistar rats were exposed to 30-minute warm ischemia in situ. Livers were then retrieved and cold-preserved for 6 hours with or without hANP supplementation. Functional and morphological integrity of the livers was evaluated by oxygenated ex vivo reperfusion at 37°C.<br />Results: hANP supplementation resulted in significant reduction of portal venous pressure (12.2 ± 0.5 versus 22.5 ± 3.5 mm Hg, P < 0.001). As underlying mechanisms, hANP supplementation significantly increased tissue adenosine concentration (P = 0.008), resulting in significant upregulation of endothelial nitric oxide synthase and significant downregulation of endothelin-1 (P = 0.01 and P = 0.004 vs. the controls, respectively). Consequently, hANP significantly decreased transaminase release (P < 0.001) and increased bile production (96.2 ± 18.2 versus 36.2 ± 15.2 μL/g-liver/h, P < 0.001). Morphologically, hepatocytes and sinusoidal endothelia were both better maintained by hANP (P = 0.021). Electron microscopy also revealed that sinusoidal ultrastructures and microvilli formation in bile canaliculi were both better preserved by hANP supplementation. Silver staining also demonstrated that hANP significantly preserved reticulin fibers in Disse space (P = 0.017), representing significant protection of sinusoidal frameworks/architectures.<br />Conclusions: Supplementation of hANP during cold storage significantly attenuated cold ischemia/warm reperfusion injury of DCD livers.
- Subjects :
- Adenosine Triphosphate chemistry
Animals
Anti-Inflammatory Agents pharmacology
Bile chemistry
Bile metabolism
Bile Duct Diseases pathology
Disease Models, Animal
Endothelium, Vascular drug effects
Humans
Inflammation
Liver drug effects
Liver enzymology
Male
Microscopy, Electron
Oxidative Stress
Oxygen
Oxygen Consumption
Perfusion
Rats
Rats, Wistar
Risk
Tissue and Organ Procurement
Warm Ischemia
Atrial Natriuretic Factor chemistry
Endothelium, Vascular pathology
Liver pathology
Organ Preservation methods
Subjects
Details
- Language :
- English
- ISSN :
- 1534-6080
- Volume :
- 103
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Transplantation
- Publication Type :
- Academic Journal
- Accession number :
- 30461725
- Full Text :
- https://doi.org/10.1097/TP.0000000000002552