Document Detail


A Recombinant Human Neuregulin-1 Peptide Improves Preservation of the Rodent Heart After Prolonged Hypothermic Storage.
MedLine Citation:
PMID:  21364498     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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-3β 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.
Authors:
Andrew Jabbour; Ling Gao; Jair Kwan; Alasdair Watson; Lin Sun; Min Ru Qiu; Xifu Liu; Ming Dong Zhou; Robert M Graham; Mark Hicks; Peter S Macdonald
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-3-1
Journal Detail:
Title:  Transplantation     Volume:  -     ISSN:  1534-6080     ISO Abbreviation:  -     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-3-2     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0132144     Medline TA:  Transplantation     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1 Heart and Lung Transplant Unit, St Vincent's Hospital and Cardiac Physiology and Transplantation Division, Victor Chang Cardiac Research Institute, Sydney, New South Wales. 2 Department of Anatomical Pathology, SydPath, St Vincent's Hospital, Sydney, New South Wales. 3 Zensun Sci and Tech Co. (Sydney) Pty Ltd., Sydney, New South Wales. 4 Department of Physiology and Pharmacology, University of New South Wales, Randwick, New South Wales.
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