Dopamine Derivate N-Octanoyl Dopamine Administration to the Transplant Recipient before the Onset of Reperfusion Improves Posttransplant Graft Function from Brain-Dead Donors in Rats

Objectives: Heart donation can currently only be considered after brain death (BD). However, 25% of potential BD donors are associated with hemodynamic instability and cardiac dysfunction. In addition, the pre-existent myocardial damage due to BD may be aggravated by hypothermic preservation/reperfusion during heart transplantation (HTX), which could affect posttransplant graft response. We recently showed that treatment of BD donors with the dopamine derivate N-octanoyl dopamine (NOD) resulted in functional recovery of grafts after cardioplegic arrest, hypothermic storage, transplantation and blood reperfusion. We hypothesized that NOD administration to the transplant recipient before the onset of reperfusion would improve graft function after HTX.

Methods: Donor rats were either exposed to sham operation (sham group, n = 8) or BD by inflation of a subdurally placed balloon catheter (BD group, n = 9), and monitored for 5.5 hours. Then, the hearts were arrested, stored for 1 hour in 4°C Custodiol cardioplegic solution, and finally heterotopically transplanted. Continuous intravenous infusion of placebo (BD + HTX group, n = 9) or NOD (0.882 mg/kg/h, BD + HTX + NOD group, n = 9) was started 5 minutes before reperfusion in the recipient rats. We evaluated in vivo left-ventricular (LV) graft function 1.5 hours after HTX via a Millar catheter system at different LV volumes.

Results: In BD donors LV systolic and diastolic parameters were significantly impaired compared to sham. After transplantation, in BD + HTX + NOD group, the grafts’ systolic function (LV systolic pressure: 90 ± 8 vs. 65 ± 4 mm Hg; maximum rate of rise of LV pressure dP/dt_max 2,686 ± 225 vs. 1,999 ± 147 mm Hg/s, p < 0.05) and diastolic function (maximum rate of fall of LV pressure dP/dt_min 1,692 ± 153 vs. 1,234 ± 101 mm Hg/s, p < 0.05) were significantly improved at an intraventricular volume of 140 µL compared with the BD + HTX group. Additionally, rebeating time (time to restoration of heartbeat) after reperfusion was significantly reduced in the BD + HTX + NOD group compared to the BD + HTX group (31.6 ± 3.8 vs. 48.0 ± 5.9 s, p < 0.05).

Conclusions: Administration of the dopamine derivate NOD to the transplant recipient before the onset of reperfusion improved posttransplant graft function from brain-dead donors in rats.