Thorac Cardiovasc Surg 2014; 62 - OP63
DOI: 10.1055/s-0034-1367140

N-octanoyl dopamine donor treatment in a brain death model in rats improves both donor and graft left ventricular function after heart transplantation

S. Li 1, 2, S. Korkmaz 1, R. Spindler 3, T. Radovits 4, S. Loganathan 1, P. Hegedüs 1, 4, L. Tao 5, B. Theisinger 6, S. Theisinger 6, S. Höger 3, M. Karck 1, B. Yard 7, G. Szabó 1
  • 1University Hospital Heidelberg, Cardiac Surgery, Heidelberg, Germany
  • 2Huazhong University of Science and Technology, Cardiovascular Surgery, Wuhan, China
  • 3University Medical Center Mannheim, Clinical Pharmacology, Mannheim, Germany
  • 4Semmelweis University, Budapest, Hungary
  • 5Wuhan Asia Heart Hospital, Cardiac Surgery, Wuhan, China
  • 6Novaliq GmbH, Heidelberg, Germany
  • 7University Medical Center Mannheim, Medicine V (Nephrology/Endocrinology/Rheumatology), Mannheim, Germany

Objectives: Heart transplantation became the most effective treatment for end-stage heart failure. Donors after brain death are currently the only reliable source for cardiac transplants. However, hemodynamic instability and cardiac dysfunction have been demonstrated in brain-dead (BD) donors and this could therefore also affect the graft response after heart transplantation. N-octanoyl dopamine (NOD), a novel dopamine derivate, has been shown to protect tissue against hypothermic preservation. We tested the hypothesis that treatment of the BD donor with NOD improves both donor cardiac and graft function after heart transplantation.

Methods: Lewis rats were administered by continuous intravenous infusion of either NOD (14.7 µg/kg.min, BD+NOD group, n = 6) or an equal volume of physiological saline (BD group: n = 9) for 5 h after brain death induction by inflation of a subdurally placed balloon catheter. Control donor rats are subjected to sham-operation (control group: n = 9). Then, hearts were excised, stored in cold preservation solution, heterotopically transplanted. Left ventricular (LV) function of the donor heart and graft was evaluated in vivo.

Results: In BD donors, decreased LV contractility and relaxation, and increased end diastolic stiffness were significantly improved after treatment with NOD (dP/dtmax: 8163 ± 696 vs. 4474 ± 359 vs. 6524 ± 773 mmHg/s; EF: 62 ± 8% vs. 30 ± 4 vs. 59 ± 8; Emax: 4.4 ± 0.4 vs. 2.1 ± 0.4 vs. 4.1 ± 0.4 mmHg/µl; PRSW: 83 ± 6 vs. 47 ± 5 vs. 77 ± 5 mmHg; dP/dtmin: -10452 ± 664 vs. -3728 ± 521 vs. -6208 ± 839 mmHg/s; and Tau: 10.1 ± 0.6 vs 14.3 ± 0.5 vs 11.4 ± 0.5 ms; control- vs. BD- vs. BD+NOD groups, respectively; P < 0.05 vs. BD group). Moreover, 90 min after transplantation, impaired systolic function and altered ventricular relaxation were also observed in BD donor group, as reflected by decreased LV systolic pressure, dP/dtmax, dP/dtmin, and prolonged Tau. NOD treatment significantly improved graft function after transplantation. Additionally, TNF-alpha, NF-KappaB, and caspase 3 protein levels assessed by Western blotting were significantly decreased by the NOD treatment compared with BD group.

Conclusion: Our data suggest that down regulation of apoptotic proteins could underline the protective effect of NOD. NOD might be a novel therapeutic approach to reduce cumulative myocardial injuries related to brain death and after heart transplantation.