Abstract 14592: Donor Treatment With N-octanoyl Dopamine in Brain-Dead Rats is Associated With an Improvement in Both Donor and Graft Left Ventricular Function After Heart Transplantation
Background: Heart transplantation is still the gold-standard therapy of terminal heart failure. Donors after brain death are currently the only reliable source for cardiac transplants. However, potential brain-dead (BD) donors associated with cardiac dysfunction are excluded from donation. 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 N-Octanoyl dopamine (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, NOD group, n=6) or an equal volume of physiological saline (BD group: n=6) for 5h after brain death induction by inflation of a subdurally placed balloon catheter. Control donor rats (control group: n=9) had intact hearts. Then, the hearts were excised, stored in cold preservation solution, heterotopically transplanted and left-ventricular function of the graft was evaluated in vivo.
Results: Altered hemodynamic parameters of BD donors were significantly increased after treatment with NOD (dP/dtmax: 7667±439 vs 4895±505 vs 6334±957 mmHg/s, dP/dtmin: 9405±418 vs 4734±575 vs 6208±839 mmHg/s, EF: 45±4% vs 27±5 vs 48±9, Emax: 4.4±0.2 vs 2.2±0.3 vs 4.1±0.4 mmHg/μl and PRSW: 94±4 vs 59±5 vs 77±5 mmHg; control vs BD vs NOD groups; P<0.05 vs BD group). After transplantation, in BD donors, NOD treatment significantly improved altered systolic function. Furthermore, significantly less DNA-strand breakage and reduced amount of inflammation were evident in NOD treated BD group. 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.
Conclusions: Our data suggest that down regulation of inflammatory, apoptotic proteins and DNA-strand breaks in myocardial tissue could underline the protective effect of NOD. Protection of cardiac donors during brain death with NOD might reduce heart transplantation associated tissue injury.
- © 2013 by American Heart Association, Inc.