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Donor preconditioning after the onset of brain death with dopamine derivate n-octanoyl dopamine improves early posttransplant graft function in the rat

Heart transplantation is the therapy of choice for end-stage heart failure. However, hemodynamic instability, which has been demonstrated in brain-dead donors (BDD), could also affect the posttransplant graft function. We tested the hypothesis that treatment of the BDD with the dopamine derivate n-o...

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Hauptverfasser: Li, Shiliang (VerfasserIn) , Korkmaz-İçöz, Sevil (VerfasserIn) , Ruppert, Mihály (VerfasserIn) , Loganathan, Sivakkanan (VerfasserIn) , Hegedűs, Péter (VerfasserIn) , Höger, Simone (VerfasserIn) , Brune, Maik (VerfasserIn) , Lasitschka, Felix (VerfasserIn) , Karck, Matthias (VerfasserIn) , Yard, Benito A. (VerfasserIn) , Szabó, Gábor (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 24 January 2017
In: American journal of transplantation
Year: 2017, Jahrgang: 17, Heft: 7, Pages: 1802-1812
ISSN:1600-6143
DOI:10.1111/ajt.14207
Online-Zugang:Verlag, Volltext: http://dx.doi.org/10.1111/ajt.14207
Verlag, Volltext: https://onlinelibrary-wiley-com.ezproxy.medma.uni-heidelberg.de/doi/abs/10.1111/ajt.14207
Volltext
Verfasserangaben:S. Li, S. Korkmaz-Icöz, T. Radovits, M. Ruppert, R. Spindler, S. Loganathan, P. Hegedűs, P. Brlecic, B. Theisinger, S. Theisinger, S. Höger, M. Brune, F. Lasitschka, M. Karck, B. Yard and G. Szabó
Beschreibung
Zusammenfassung:Heart transplantation is the therapy of choice for end-stage heart failure. However, hemodynamic instability, which has been demonstrated in brain-dead donors (BDD), could also affect the posttransplant graft function. We tested the hypothesis that treatment of the BDD with the dopamine derivate n-octanoyl-dopamine (NOD) improves donor cardiac and graft function after transplantation. Donor rats were given a continuous intravenous infusion of either NOD (0.882 mg/kg/h, BDD+NOD, n = 6) or a physiological saline vehicle (BDD, n = 9) for 5 h after the induction of brain death by inflation of a subdural balloon catheter. Controls were sham-operated (n = 9). In BDD, decreased left-ventricular contractility (ejection fraction; maximum rate of rise of left-ventricular pressure; preload recruitable stroke work), relaxation (maximum rate of fall of left-ventricular pressure; Tau), and increased end-diastolic stiffness were significantly improved after the NOD treatment. Following the transplantation, the NOD-treatment of BDD improved impaired systolic function and ventricular relaxation. Additionally, after transplantation increased interleukin-6, tumor necrosis factor TNF-α, NF-kappaB-p65, and nuclear factor (NF)-kappaB-p105 gene expression, and increased caspase-3, TNF-α and NF-kappaB protein expression could be significantly downregulated by the NOD treatment compared to BDD. BDD postconditioning with NOD through downregulation of the pro-apoptotic factor caspase-3, pro-inflammatory cytokines, and NF-kappaB may protect the heart against the myocardial injuries associated with brain death and ischemia/reperfusion.
Beschreibung:Gesehen am 20.07.2018
First published: 24 January 2017
Beschreibung:Online Resource
ISSN:1600-6143
DOI:10.1111/ajt.14207

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