A Recombinant Human Neuregulin-1 Peptide Improves Preservation of the Rodent Heart After Prolonged Hypothermic Storage

作者：Andrew Jabbour, Ling Gao, J. Kwan, Alasdair Watson, Lin Sun, Min Qiu, Xifu Liu, Ming Zhou, Robert M. Graham, Mark Hicks, Peter S. Macdonald · 发表于：Transplantation · 年份：2011 · DOI：10.1097/tp.0b013e3182115b4b · 被引用次数：25 · 研究领域：Transplantation: Methods and Outcomes、Cardiac Fibrosis and Remodeling、Viral Infections and Immunology Research

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 furthe...