Dimethyloxalylglycine treatment of brain-dead donor rats improves both donor and graft left ventricular function after heart transplantation

• Verfasst von: Hegedűs, Péter [VerfasserIn]
• Verfasst von: Li, Shiliang [VerfasserIn]
• Verfasst von: Korkmaz-İçöz, Sevil [VerfasserIn]
• Verfasst von: Radovits, Tamás [VerfasserIn]
• Verfasst von: Mayer, Tobias [VerfasserIn]
• Verfasst von: Al Said, Samer [VerfasserIn]
• Verfasst von: Brlecic, Paige [VerfasserIn]
• Verfasst von: Karck, Matthias [VerfasserIn]
• Verfasst von: Merkely, Béla [VerfasserIn]
• Verfasst von: Szabó, Gábor [VerfasserIn]
• Titel: Dimethyloxalylglycine treatment of brain-dead donor rats improves both donor and graft left ventricular function after heart transplantation
• Verf.angabe: Péter Hegedűs, Shiliang Li, Sevil Korkmaz-Icöz, Tamás Radovits, Tobias Mayer, Samer Al Said, Paige Brlecic, Matthias Karck, Béla Merkely, Gábor Szabó
• Jahr: 2016
• Jahr des Originals: 2015
• Umfang: 9 S.
• Fussnoten: Available online 4 July 2015 ; Gesehen am 07.05.2020
• Titel Quelle: Enthalten in: The journal of heart and lung transplantation
• Ort Quelle: Amsterdam [u.a.] : Elsevier Science, 1999
• Jahr Quelle: 2016
• Band/Heft Quelle: 35(2016), 1, Seite 99-107
• ISSN Quelle: 1557-3117
• DOI: doi:10.1016/j.healun.2015.06.016
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: DMOG
• Sach-SW: graft function
• Sach-SW: heart transplantation
• Sach-SW: HIF-1
• Sach-SW: ischemia-reperfusion injury
• K10plus-PPN: 1697687164

Abstract

Objective - Hypoxia inducible factor (HIF)-1 pathway signalling has a protective effect against ischemia/reperfusion injury. The prolyl-hydroxylase inhibitor dimethyloxalylglycine (DMOG) activates the HIF-1 pathway by stabilizing HIF-1α. In a rat model of brain death (BD)-associated donor heart dysfunction we tested the hypothesis that pre-treatment of brain-dead donors with DMOG would result in a better graft heart condition. - Methods - BD was induced in anesthetized Lewis rats by inflating a subdurally placed balloon catheter. Controls underwent sham operations. Then, rats were injected with an intravenous dose of DMOG (30 mg/kg) or an equal volume of physiologic saline. After 5 hours of BD or sham operation, hearts were perfused with a cold (4°C) preservation solution (Custodiol; Dr. Franz Köhler Chemie GmbH; Germany), explanted, stored at 4°C in Custodiol, and heterotopically transplanted. Graft function was evaluated 1.5 hours after transplantation. - Results - Compared with control, BD was associated with decreased left ventricular systolic and diastolic function. DMOG treatment after BD improved contractility (end-systolic pressure volume relationship E’max: 3.7 ± 0.6 vs 3.1 ± 0.5 mm Hg/µ1; p < 0.05) and left ventricular stiffness (end-diastolic pressure volume relationship: 0.13 ± 0.03 vs 0.31 ± 0.06 mm Hg/µ1; p < 0.05) 5 hours later compared with the brain-dead group. After heart transplantation, DMOG treatment of brain-dead donors significantly improved the altered systolic function and decreased inflammatory infiltration, cardiomyocyte necrosis, and DNA strand breakage. In addition, compared with the brain-dead group, DMOG treatment moderated the pro-apoptotic changes in the gene and protein expression. - Conclusions - In a rat model of potential brain-dead heart donors, pre-treatment with DMOG resulted in improved early recovery of graft function after transplantation. These results support the hypothesis that activation of the HIF-1 pathway has a protective role against BD-associated cardiac dysfunction.