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Recipient hyperbilirubinaemia protects cardiac graft in rat heterotopic heart transplantation.

Authors
 Sungsoo Lee  ;  Taihei Yamada  ;  Takaaki Osako  ;  Donna B. Stolz  ;  Masanori Abe  ;  Kenneth R. McCurry  ;  Noriko Murase  ;  Joji Kotani  ;  Atsunori Nakao 
Citation
 EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY, Vol.45(3) : 481-488, 2014 
Journal Title
 EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY 
ISSN
 1010-7940 
Issue Date
2014
MeSH
Animals ; Apoptosis ; Cell Proliferation ; Cytokines/metabolism ; Graft Survival/physiology* ; Heart Transplantation* ; Hyperbilirubinemia/metabolism* ; Lipid Peroxidation ; Male ; Rats ; Rats, Transgenic ; Reperfusion Injury/metabolism* ; Transplantation, Heterotopic* ; Transplantation, Homologous
Keywords
Heart transplantation ; Hyperbilirubinaemia ; Ischaemia reperfusion
Abstract
OBJECTIVES: Since bilirubin is a known powerful antioxidant, this study examined whether recipient hyperbilirubinaemia protected heart grafts from ischaemia/reperfusion (I/R) injury and chronic rejection associated with rat cardiac transplantation. METHODS: Heterotopic heart transplantation (HTx) was performed using congenitally hyperbilirubinaemic GUNN (j/j) and normobilirubinaemic GUNN (+/+) rats. Syngenic grafts from +/+ rats were transplanted into +/+ or j/j rats with 6 or 18 h cold storage in University of Wisconsin solution to study I/R injury. To evaluate the effect on chronic rejection, Brown Norway rat heart grafts were transplanted into +/+ or j/j rats under short-course tacrolimus immunosuppression. RESULTS: The +/+ grafts in j/j rats demonstrated significantly lower serum creatine phosphokinase and higher left ventricular developed pressures and had smaller infarct areas than +/+ rats at 3 h after reperfusion. Graft survival with 18 h cold storage increased from 0% in +/+ rats to 41.7% in j/j rats. Malondialdehyde (a marker of lipid peroxidation), mRNA of the inflammatory mediators and phosphorylation of ERK1/2 were significantly decreased in the grafts transplanted into j/j rats compared with those transplanted into +/+ rats 1-3 h after reperfusion. The mean allograft survival in j/j recipients was prolonged to a median survival of 150 days from 84 days in +/+ recipients and was associated with less macrophage infiltrates and less intragraft inflammatory cytokine mRNA at d60. In vitro T-cell proliferation was significantly inhibited in the presence of bilirubin. CONCLUSIONS: Recipient hyperbilirubinaemia ameliorated cardiac I/R injury, as well as chronic allograft rejection following HTx via regulation of inflammatory responses or T-cell proliferation.
Full Text
http://ejcts.oxfordjournals.org/content/45/3/481
DOI
10.1093/ejcts/ezt402
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Thoracic and Cardiovascular Surgery (흉부외과학교실) > 1. Journal Papers
Yonsei Authors
Lee, Sung Soo(이성수) ORCID logo https://orcid.org/0000-0001-8998-9510
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/138975
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