n-octanoyl dopamine, a non-hemodyanic dopamine derivative, for cell protection during hypothermic organ preservationnon-hemodyanic n-octanoyl多巴胺,多巴胺衍生物,保护细胞在低温器官保存.pdfVIP

N-Octanoyl Dopamine, a Non-Hemodyanic Dopamine Derivative, for Cell Protection during Hypothermic Organ Preservation ¨ 1 . 2. 2,5. 2,4. 3 2 Ralf M. Losel * , Ulf Schnetzke , Paul T. Brinkkoetter , Hui Song , Grietje Beck , Peter Schnuelle , ¨ 2 1 2 Simone Hoger , Martin Wehling , Benito A. Yard 1 Department of Clinical Pharmacology, University Medical Centre Mannheim, Mannheim, Germany, 2 Department of Nephrology, University Medical Centre Mannheim, Mannheim, Germany, 3 Department of Anaesthesiology, University Medical Centre Mannheim, Mannheim, Germany, 4 School of Dentistry, Shandong University, Jinan, People’s Republic of China, 5 Department of Medicine, Centre for Molecular Medicine and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany Abstract Background: Although donor dopamine treatment reduces the requirement for post transplantation dialysis in renal transplant recipients, implementation of dopamine in donor management is hampered by its hemodynamic side-effects. Therefore novel dopamine derivatives lacking any hemodynamic actions and yet are more efficacious in protecting tissue from cold preservation injury are warranted. We hypothesized that variation of the molecular structure would yield more efficacious compounds avoid of any hemodynamic effects. Methodology/Principal Findings: To this end, we assessed protection against cold preservation injury in HUVEC by the attenuation of lactate dehydrogenase (LDH) release. Modification of dopamine by an alkanoyl group increased cellular uptake and significantly improved effic