Recipient Treatment with n-octanoyl Dopamine Improves Post Transplant Graft Function from Brain-Dead Heart Donor in Rats

Abstract

Purpose Currently, only the hearts of brain-dead (BD) donors are used for transplantation. However, hemodynamic instability and cardiac dysfunction occur in 1/4 of these donors. Myocardial ischemia/reperfusion injury encountered at the time of heart transplantation (HTX) lead to further impairment, contributing to adverse short- and long-term graft outcome in the recipients. Our previous study demonstrated that BD donors’ treatment with dopamine derivate n-octanoyl dopamine (NOD) contributes to the functional recovery of grafts after transplantation. Taken together, we hypothesized that recipient treatment with NOD would improve graft function after transplantation. Methods Donor rats were either subjected to BD via inflation of subdurally placed balloon or sham operation, followed by 5.5h monitoring. After cardiac arrest, the hearts were explanted and stored for 1h in cold Custodiol cardioplegic solution, finally heterotopically transplanted. Five minutes before the onset of reperfusion, continuous intravenous infusion of NOD (0.882 mg/kg/h, BD+HTX+NOD group, n=9) or placebo (BD+HTX group, n=9) were administered to the recipient rats. In vivo left-ventricular (LV) graft function was evaluated 1.5h after reperfusion via a Millar catheter system at different LV volumes. Results BD adversely affected hemodynamic parameters in heart donors compared with the sham group. After transplantation, a significantly improved graft systolic function (LV systolic pressure 90±8 vs 65±4 mmHg; maximum rate of rise of LV pressure dP/dtmax 2686±225 vs 1999±147 mmHg/s, at an intraventricular volume of 140 µl, p Conclusion Our data demonstrate that recipient treatment with the dopamine derivate NOD before the onset of reperfusion improves posttransplant function of hearts derived from BD donors in rats.