Thorac Cardiovasc Surg 2020; 68(S 01): S1-S72
DOI: 10.1055/s-0040-1705470
Short Presentations
Sunday, March 1st, 2020
Cardiovascular Basic Sciences
Georg Thieme Verlag KG Stuttgart · New York

N-Octanoyl Dopamine Is Superior to Dopamine in Protecting Graft Contractile Function when Administered to the Heart Transplant Recipients from Brain-Dead Donors

Y. Guo
1   Heidelberg, Germany
,
S. Korkmaz-Icöz
1   Heidelberg, Germany
,
W. Jiang
1   Heidelberg, Germany
,
P. Brlecic
1   Heidelberg, Germany
,
T. Radovits
2   Budapest, Hungary
,
M. Brune
1   Heidelberg, Germany
,
B. Yard
3   Mannheim, Germany
,
M. Karck
1   Heidelberg, Germany
,
S. Loganathan
1   Heidelberg, Germany
,
G. Szabó
1   Heidelberg, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
13 February 2020 (online)

Objectives: The major source of heart transplantation (HTX) comes from brain-dead (BD) donors. However, brain death and myocardial ischemia/reperfusion injury may lead to cardiac dysfunction and hemodynamic instability. A previous work demonstrated that pretreatment of BD donors with dopamine improved the graft survival of heart allograft recipient after HTX. However, low-dose dopamine treatment might result in tachycardia and hypertension. Our previous study showed that pretreatment of BD donor rats with dopamine derivative n-octanoyl dopamine (NOD), devoid of any hemodynamic effects, improved graft function after HTX. Herein, we hypothesized that NOD confers superior myocardial protection and improved graft function than dopamine, when administered to the heart transplant recipients from BD donors.

Methods: Male Lewis donor rats were subjected to either sham operation or brain death via a subdurally placed balloon followed by 5.5 hours of monitoring. Then, the hearts were explanted and heterotopically transplanted into Lewis recipient rats. Shortly before the onset of reperfusion, continuous intravenous infusion of NOD (14.7 μg/kg/min, BD + NOD group, n = 9), dopamine (10 μg/kg/min, BD + dopamine group, n = 8), or physiological saline vehicle (sham, n = 9 and BD, n = 9) was administered to the recipient rats. In vivo left-ventricular (LV) graft function was evaluated after the 1.5-hour reperfusion. Additionally, immunohistochemical detection of 4-hydroxynonenal (HNE, an indicator of oxidative stress) and nitrotyrosine (a nitro-oxidative stress marker) was performed.

Results: After HTX, systolic and diastolic functions were significantly decreased in the BD group compared to sham. Treatment with NOD but not dopamine resulted in better LV graft systolic functional recovery (LV systolic pressure BD + NOD 90 ± 8 vs. BD + dopamine 66 ± 5 vs. BD 65 ± 4 mm Hg; maximum rate of rise of LV pressure dP/dtmax BD + NOD 2,686 ± 225 vs. BD + dopamine 2,243 ± 70 vs. BD 1,999 ± 147 mm Hg/s, at an intraventricular volume of 140 μL, p < 0.05) and myocardial work compared to BD group. The re-beating time was significantly shorter in BD + NOD group than that of BD hearts (32 ± 4 vs. 48 ± 6 s, p < 0.05). Dopamine treatment had no impact on these parameters. Furthermore, NOD as well as dopamine decreased HNE and nitrotyrosine immunostaining to the same level.

Conclusion: NOD is superior to dopamine in protecting LV graft contractile function, when administered to the heart transplant recipients from BD donors.