Document Detail

Cardioprotective efficacy depends critically on pharmacological dose, duration of ischaemia, health status of animals and choice of anaesthetic regimen: a case study with folic acid.
MedLine Citation:
PMID:  25432364     Owner:  NLM     Status:  Publisher    
BackgroundAcute, high-dose folic acid (FA) administration has recently been shown to possess unprecedented effective cardioprotection against ischaemia/reperfusion (I/R) injury. Here we explore the translation potential of FA as treatment modality for cardiac I/R.MethodsDependency of FA protection on dose, ischaemia duration, and eNOS was examined in an isolated mouse heart I/R model, whereas dependency on animal health status and anaesthesia was examined in an in vivo rat model of regional cardiac I/R.Results50 ¿M FA provided maximal reduction (by 95%) of I/R-induced cell death following 25 min ischaemia in isolated wild-type hearts, with protection associated with increased coupled eNOS protein. No protection was observed with 35 min I or in eNOS¿/¿ hearts. Acute intravenous administration of FA during a 25 min ischaemic period reduced infarct size by 45% in in vivo pentobarbital-anaesthetised young, healthy rats. FA did not reduce infarct size in aged or pre-diabetic rats, although it did preserve hemodynamics in the pre-diabetic rats. Finally, using a clinically-relevant anaesthetic regimen of fentanyl-propofol anaesthesia, FA treatment was ineffective in young, aged and pre-diabetic animals.ConclusionsThe protective potential of an initially promising cardioprotective treatment of high dose FA against cardiac I/R infarction, is critically dependent on experimental conditions with relevance to the clinical condition. Our data indicates the necessity of expanded pre-clinical testing of cardioprotective interventions before embarking on clinical testing, in order to prevent too many ¿lost-in-translation¿ drugs and unnecessary clinical studies.
Coert J Zuurbier; Andre Heinen; Anneke Koeman; Roy Stuifbergen; Theodorus Hakvoort; Nina C Weber; Markus W Hollmann
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-11-29
Journal Detail:
Title:  Journal of translational medicine     Volume:  12     ISSN:  1479-5876     ISO Abbreviation:  J Transl Med     Publication Date:  2014 Nov 
Date Detail:
Created Date:  2014-11-29     Completed Date:  -     Revised Date:  2014-11-30    
Medline Journal Info:
Nlm Unique ID:  101190741     Medline TA:  J Transl Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  325     Citation Subset:  -    
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