title: Donor Preconditioning After the Onset of Brain Death With Dopamine Derivate n-Octanoyl Dopamine Improves Early Posttransplant Graft Function in the Rat.
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.
authors.affiliation: Department of Cardiac Surgery, University Hospital Heidelberg, Heidelberg, Germany.|Department of Cardiovascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: S
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Cardiac Surgery, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Korkmaz-Icöz
authors.affiliation: Heart and Vascular Center, Semmelweis University, Budapest, Hungary.
authors.forename: T
authors.initials: T
authors.lastname: Radovits
authors.affiliation: Department of Cardiac Surgery, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Ruppert
authors.affiliation: Department of Medicine V (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, Mannheim, Germany.
authors.forename: R
authors.identifier: http://orcid.org/0000-0002-7292-1752
authors.initials: R
authors.lastname: Spindler
authors.affiliation: Department of Cardiac Surgery, University Hospital Heidelberg, Heidelberg, Germany.|Department of Anesthesiology, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Loganathan
authors.affiliation: Department of Cardiac Surgery, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Hegedűs
authors.affiliation: Department of Cardiac Surgery, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Brlecic
authors.affiliation: Novaliq GmbH, Heidelberg, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Theisinger
authors.affiliation: Novaliq GmbH, Heidelberg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Theisinger
authors.affiliation: Department of Medicine V (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, Mannheim, Germany.|Department of Clinical Pharmacology, University Medical Centre Mannheim, Mannheim, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Höger
authors.affiliation: Department of Medicine I and Clinical Chemistry, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Brune
authors.affiliation: Institute of Pathology, University Heidelberg, Heidelberg, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Lasitschka
authors.affiliation: Department of Cardiac Surgery, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Karck
authors.affiliation: Department of Medicine V (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, Mannheim, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Yard
authors.affiliation: Department of Cardiac Surgery, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Szabó
mesh_terms: D000818:Animals; D001926:Brain Death; D053148:Caspase 3 / Q000378:metabolism; D004298:Dopamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016027:Heart Transplantation / Q000379:methods*; D015850:Interleukin-6 / Q000378:metabolism; D019194:Ischemic Preconditioning; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000517:prevention & control*; D014019:Tissue Donors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology*
chemical_list: D015850:Interleukin-6; C554838:N-octanoyldopamine; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D053148:Caspase 3; D004298:Dopamine
keywords: animal models; basic (laboratory) research/science; donors and donation: donation after brain death (DBD); heart (allograft) function/dysfunction; heart transplantation/cardiology