dc.contributor.author |
Hegedűs, Péter |
|
dc.contributor.author |
Li S |
|
dc.contributor.author |
Korkmaz-Icöz S |
|
dc.contributor.author |
Radovits, Tamás |
|
dc.contributor.author |
Mayer T |
|
dc.contributor.author |
Al Said S |
|
dc.contributor.author |
Brlecic P |
|
dc.contributor.author |
Karck M |
|
dc.contributor.author |
Merkely, Béla Péter |
|
dc.contributor.author |
Szabó, Gábor Balázs |
|
dc.date.accessioned |
2018-08-09T10:24:07Z |
|
dc.date.available |
2018-08-09T10:24:07Z |
|
dc.date.issued |
2016 |
|
dc.identifier |
84954077986 |
|
dc.identifier.citation |
pagination=99-107;
journalVolume=35;
journalIssueNumber=1;
journalTitle=JOURNAL OF HEART AND LUNG TRANSPLANTATION; |
|
dc.identifier.uri |
http://repo.lib.semmelweis.hu//handle/123456789/5790 |
|
dc.identifier.uri |
doi:10.1016/j.healun.2015.06.016 |
|
dc.description.abstract |
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. |
|
dc.relation.ispartof |
urn:issn:1053-2498 |
|
dc.title |
Dimethyloxalylglycine treatment of brain-dead donor rats improves both donor and graft left ventricular function after heart transplantation. |
|
dc.type |
Journal Article |
|
dc.date.updated |
2018-07-13T07:41:34Z |
|
dc.language.rfc3066 |
en |
|
dc.identifier.mtmt |
2927507 |
|
dc.identifier.wos |
000370113600013 |
|
dc.identifier.pubmed |
26255815 |
|
dc.contributor.department |
SE/AOK/K/VAROSMAJOR_SZÍVÉRGYÓGY/Kardiológia Központ - Kardiológiai Tanszék [2017.10.31] |
|
dc.contributor.institution |
Semmelweis Egyetem |
|