A recombinant human neuregulin-1 peptide improves preservation of the rodent heart after prolonged hypothermic storage.
Transplantation
; 91(9): 961-7, 2011 May 15.
Article
em En
| MEDLINE
| ID: mdl-21364498
ABSTRACT
BACKGROUND:
Donor hearts are subjected to ischemia-reperfusion injury during transplantation. Recombinant human neuregulin (rhNRG)-1 peptide attenuates myocardial injury in various animal models of cardiomyopathy. Supplementing the organ-storage solution, Celsior (C), with glyceryl trinitrate (GTN) and cariporide improves cardiac preservation after hypothermic storage. We hypothesized that the addition of rhNRG-1 to C would improve cardiac preservation after hypothermic storage and provide incremental benefit in combination with GTN and cariporide.METHODS:
An isolated working rat heart model was used. To assess the effect of rhNRG-1, hearts were stored for 6 hr at 4°C in C ± rhNRG-1 (14 nM). To assess the effect of using a combination of prosurvival kinase activators on cardiac preservation, the ischemic storage time was extended to 10 hr and hearts stored in C ± rhNRG-1 (14 nM) ± GTN (0.1 mg/mL) ± Cariporide (10 µM). Hearts were subsequently reperfused, cardiac function remeasured, and tissue collected for protein analysis and immunohistochemistry. Optimal timing of rhNRG-1 administration was also assessed.RESULTS:
rhNRG-1 supplemented C improved functional recovery after 6 hr of storage (cardiac output recovery [mean ± SEM] control 1.4% ± 0.6%; rhNRG-1+C 21.1% ± 7.9%; P<0.05). After 10-hr storage, no improvement in functional recovery was observed with rhNRG-1, GTN, or cariporide alone; however, GTN combined with cariporide did improve recovery (P<0.01), which was further enhanced by the addition of rhNRG-1 (P<0.01). Functional improvements were accompanied by increased phosphorylation of Akt, ERK1/2, STAT3, and GSK-3ß and reduced cleaved caspase-3 (P<0.01).CONCLUSIONS:
rhNRG-1 given together with other activators of prosurvival pathways improves preservation of the rat heart and shows promise for increasing the cold-ischemic life of donor hearts in transplantation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Preservação de Órgãos
/
Neuregulina-1
/
Coração
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Transplantation
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Austrália