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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

Overview of attention for article published in Journal of Translational Medicine, November 2014
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Title
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
Published in
Journal of Translational Medicine, November 2014
DOI 10.1186/s12967-014-0325-8
Pubmed ID
Authors

Coert J Zuurbier, Andre Heinen, Anneke Koeman, Roy Stuifbergen, Theodorus BM Hakvoort, Nina C Weber, Markus W Hollmann

Abstract

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.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 18 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 18 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 4 22%
Researcher 3 17%
Other 2 11%
Student > Ph. D. Student 1 6%
Librarian 1 6%
Other 2 11%
Unknown 5 28%
Readers by discipline Count As %
Medicine and Dentistry 4 22%
Biochemistry, Genetics and Molecular Biology 3 17%
Pharmacology, Toxicology and Pharmaceutical Science 2 11%
Agricultural and Biological Sciences 2 11%
Chemical Engineering 1 6%
Other 0 0%
Unknown 6 33%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 30 November 2014.
All research outputs
#20,245,139
of 22,772,779 outputs
Outputs from Journal of Translational Medicine
#3,306
of 3,984 outputs
Outputs of similar age
#303,053
of 361,775 outputs
Outputs of similar age from Journal of Translational Medicine
#86
of 114 outputs
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