ArticleJournal of translational medicine2014
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.
Article in Journal of translational medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- Cardioprotective efficacy of limb remote ischaemic preconditioning in rats: discrepancy between a meta-analysis and a three-centre in vivo study.Cardiovascular research · 2023Pooled it
- Unravelling mitochondrial succinate transport during I/R and devising a novel transport inhibitor show promise for targeting I/R injury, but will efficacy remain under more human-like conditions present during I/R?Cardiovascular research · 2026Article
- The Protective Effects of Carvacrol Against Doxorubicin-Induced Cardiotoxicity In Vitro and In Vivo.Cardiovascular toxicology · 2025Article
- Propofol Suppresses Ferroptosis via Modulating eNOS/NO Signaling Pathway to Improve Traumatic Brain Injury.Brain and behavior · 2024Article
- Review
- Interaction of Cardiovascular Nonmodifiable Risk Factors, Comorbidities and Comedications With Ischemia/Reperfusion Injury and Cardioprotection by Pharmacological Treatments and Ischemic Conditioning.Pharmacological reviews · 2023Review
- Differential effects of speed and volume on transfusion-associated circulatory overload: A randomized study in rats.Vox sanguinis · 2022Article
- The Redox Modulating Sonlicromanol Active Metabolite KH176m and the Antioxidant MPG Protect Against Short-Duration Cardiac Ischemia-Reperfusion Injury.Cardiovascular drugs and therapy · 2021Article
- Cardioprotecive Properties of Known Agents in Rat Ischemia-Reperfusion Model Under Clinically Relevant Conditions: Only the NAD Precursor Nicotinamide Riboside Reduces Infarct Size in Presence of Fentanyl, Midazolam and Cangrelor, but Not Propofol.Frontiers in cardiovascular medicine · 2021Article
- Ageing, sex, and cardioprotection.British journal of pharmacology · 2020Review
- NLRX1 Deletion Increases Ischemia-Reperfusion Damage and Activates Glucose Metabolism in Mouse Heart.Frontiers in immunology · 2020Article
- Volume incompliance and transfusion are essential for transfusion-associated circulatory overload: a novel animal model.Transfusion · 2019Article
- Reduced acute myocardial ischemia-reperfusion injury in IL-6-deficient mice employing a closed-chest model.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2016Article
- Mitochondrial involvement in propofol-induced cardioprotection: An in vitro study in human myocardium.Experimental biology and medicine (Maywood, N.J.) · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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 μM 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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.