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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.

Research paper by Shiliang S Li, Sevil S Korkmaz-Icöz, Tamás T Radovits, Mihály M Ruppert, Rahel R Spindler, Sivakkanan S Loganathan, Péter P Hegedűs, Paige P Brlecic, Bastian B Theisinger, Sonja S Theisinger, Simone S Höger, Maik M Brune, Felix F Lasitscha, Matthias M Karck, Benito B Yard, et al.

Indexed on: 25 Jan '17Published on: 25 Jan '17Published in: American Journal of Transplantation



Abstract

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 (0.882mg/kg/h, BDD+NOD, n=6) or a physiological saline vehicle (BDD, n=9) for 5h 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, TNF-α, NF-kappaB-p65 and NF-kappaB-p105 gene expression, and increased caspase-3, TNF-α and NF-KappaB protein expression could be significantly down-regulated by the NOD-treatment compared to BDD. BDD post-conditioning with NOD through down-regulation 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. This article is protected by copyright. All rights reserved.