Donor Preconditioning After the Onset of Brain Death With Dopamine Derivate n-Octanoyl Dopamine Improves Early Posttransplant Graft Function in the Rat

S. Li, S. Korkmaz-Icöz, T. Radovits, M. Ruppert, R. Spindler, S. Loganathan, P. Hegedus, P. Brlecic, B. Theisinger, S. Theisinger, S. Höger, M. Brune, F. Lasitschka, M. Karck, B. Yard, G. Szabó

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13 Citations (Scopus)

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 (0.882 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.

Original languageEnglish
JournalAmerican Journal of Transplantation
DOIs
Publication statusAccepted/In press - 2017

Keywords

  • Animal models
  • Basic (laboratory) research/science
  • Donors and donation: donation after brain death (DBD)
  • Heart (allograft) function/dysfunction
  • Heart transplantation/cardiology

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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    Li, S., Korkmaz-Icöz, S., Radovits, T., Ruppert, M., Spindler, R., Loganathan, S., Hegedus, P., Brlecic, P., Theisinger, B., Theisinger, S., Höger, S., Brune, M., Lasitschka, F., Karck, M., Yard, B., & Szabó, G. (Accepted/In press). Donor Preconditioning After the Onset of Brain Death With Dopamine Derivate n-Octanoyl Dopamine Improves Early Posttransplant Graft Function in the Rat. American Journal of Transplantation. https://doi.org/10.1111/ajt.14207