ArticlePloS one2016
Protective Effect of Creatine Elevation against Ischaemia Reperfusion Injury Is Retained in the Presence of Co-Morbidities and during Cardioplegia.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 11 citations in OpenAlex.
- Maintaining energy provision in the heart: the creatine kinase system in ischaemia-reperfusion injury and chronic heart failure.Clinical science (London, England : 1979) · 2024Review
- Synergistic effect on cardiac energetics by targeting the creatine kinase system: in vivo application of high-resolutionJournal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance · 2023Article
- Creatine Supplementation for Patients with Inflammatory Bowel Diseases: A Scientific Rationale for a Clinical TrialNutrients · 2021Review
- Non-invasive investigation of myocardial energetics in cardiac disease usingCardiovascular diagnosis and therapy · 2020Review
- Ischemia and reperfusion injury following cardioplegic arrest is attenuated by age and testosterone deficiency in male but not female mice.Biology of sex differences · 2019Article
- The creatine kinase system as a therapeutic target for myocardial ischaemia-reperfusion injury.Biochemical Society transactions · 2018Review
- Superior diastolic function with KThe Journal of surgical research · 2018Article
- Over-expression of mitochondrial creatine kinase in the murine heart improves functional recovery and protects against injury following ischaemia-reperfusion.Cardiovascular research · 2018Article
- Proteomic and metabolomic changes driven by elevating myocardial creatine suggest novel metabolic feedback mechanisms.Amino acids · 2016Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
aimsIschaemic heart disease is most prevalent in the ageing population and often exists with other comorbidities; however the majority of laboratory research uses young, healthy animal models. Several recent workshops and focus meetings have highlighted the importance of using clinically relevant models to help aid translation to realistic patient populations. We have previously shown that mice over-expressing the creatine transporter (CrT-OE) have elevated intracellular creatine levels and are protected against ischaemia-reperfusion injury. Here we test whether elevating intracellular creatine levels retains a cardioprotective effect in the presence of common comorbidities and whether it is additive to protection afforded by hypothermic cardioplegia. METHODS AND
resultsCrT-OE mice and wild-type controls were subjected to transverse aortic constriction for two weeks to induce compensated left ventricular hypertrophy (LVH). Hearts were retrogradely perfused in Langendorff mode for 15 minutes, followed by 20 minutes ischaemia and 30 minutes reperfusion. CrT-OE hearts exhibited significantly improved functional recovery (Rate pressure product) during reperfusion compared to WT littermates (76% of baseline vs. 59%, respectively, P = 0.02). Aged CrT-OE mouse hearts (78±5 weeks) also had enhanced recovery following 15 minutes ischaemia (104% of baseline vs. 67%, P = 0.0007). The cardioprotective effect of hypothermic high K+ cardioplegic arrest, as used during cardiac surgery and donor heart transplant, was further enhanced in prolonged ischaemia (90 minutes) in CrT-OE Langendorff perfused mouse hearts (76% of baseline vs. 55% of baseline as seen in WT hearts, P = 0.02).
conclusionsThese observations in clinically relevant models further support the development of modulators of intracellular creatine content as a translatable strategy for cardiac protection against ischaemia-reperfusion injury.
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