Document Detail


Reduction of hyperacute rejection and protection of metabolism and function in hearts of human decay accelerating factor (hDAF)-expressing pigs.
MedLine Citation:
PMID:  17134686     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: The use of pig hearts can solve the problem of shortage of donor hearts for transplantation. However, targeting rejection by single genetic modification was proven to be ineffective, highlighting the requirement for complex genetic modifications and more effective methods for transgenic animal production. We evaluated here whether hearts of hDAF transgenic pigs generated using our technique sperm-mediated gene transfer (SMGT) will be protected from structural damage, metabolic changes, and mechanical dysfunction during perfusion with human blood.
METHODS: Hearts from control (C, n = 6) or transgenic (T, n = 5) pigs were perfused ex vivo for 4 h with fresh human blood using the ex vivo working mode system allowing monitoring of the function, metabolism, and structure.
RESULTS: Cardiac output (mean+/-SEM) was maintained in T constant throughout the experiment, at 3.58+/-0.36 and 3.83+/-0.14 l/min after 30 min and 4 h, respectively, while cardiac output decreased to 1.95+/-0.35 l/min in C after 30 min of perfusion (p < 0.01 vs. T). The maximum increase in coronary perfusion pressure was reduced in T to 154+/-16% as compared to C (237+/-10%, p < 0.001). Myocardial ATP after 4 h was 21.1+/-1.1 nmol/mg dry wt (similar to initial) in T, while it decreased in C to 17.2+/-1.4 (p < 0.05). Deposition of complement factors C3 and C5b9 was present in C but not in T after perfusion.
CONCLUSION: We have shown that hearts from hDAF transgenic pigs produced by SMGT are protected during perfusion with human blood and are metabolically stable and maintain mechanical function above the threshold level for life support.
Authors:
Ryszard T Smolenski; Monica Forni; Massimo Maccherini; Maria Laura Bacci; Ewa M Slominska; Hongjun Wang; Piermaria Fornasari; Roberto Giovannoni; Felicetta Simeone; Augusta Zannoni; Giacomo Frati; Ken Suzuki; Magdi H Yacoub; Marialuisa Lavitrano
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-11-06
Journal Detail:
Title:  Cardiovascular research     Volume:  73     ISSN:  0008-6363     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2006-12-25     Completed Date:  2007-04-10     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  143-52     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Acute Disease
Animals
Animals, Genetically Modified
Antigens, CD55 / analysis,  genetics,  metabolism*
Breeding
Female
Gene Expression
Graft Rejection / prevention & control*
Heart Transplantation*
Humans
Immunohistochemistry / methods
Insemination, Artificial
Male
Models, Animal
Myocardium / chemistry,  metabolism*
Perfusion
Spermatozoa / metabolism
Swine
Transduction, Genetic / methods
Transplantation, Heterologous
Grant Support
ID/Acronym/Agency:
G116/158//Medical Research Council
Chemical
Reg. No./Substance:
0/Antigens, CD55

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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