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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.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 17 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 17 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 4 24%
Researcher 3 18%
Other 2 12%
Student > Ph. D. Student 1 6%
Librarian 1 6%
Other 2 12%
Unknown 4 24%
Readers by discipline Count As %
Medicine and Dentistry 5 29%
Pharmacology, Toxicology and Pharmaceutical Science 2 12%
Biochemistry, Genetics and Molecular Biology 2 12%
Agricultural and Biological Sciences 2 12%
Chemical Engineering 1 6%
Other 0 0%
Unknown 5 29%

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
#18,968,119
of 21,321,365 outputs
Outputs from Journal of Translational Medicine
#3,055
of 3,686 outputs
Outputs of similar age
#289,281
of 344,931 outputs
Outputs of similar age from Journal of Translational Medicine
#226
of 326 outputs
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