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Aims: Mitochondrial creatine kinase (MtCK) couples ATP production via oxidative phosphorylation to phosphocreatine in the cytosol, which acts as a mobile energy store available for regeneration of ATP at times of high demand. We hypothesized that elevating MtCK would be beneficial in ischaemia-reperfusion (I/R) injury. Methods and results: Mice were created over-expressing the sarcomeric MtCK gene with αMHC promoter at the Rosa26 locus (MtCK-OE) and compared with wild-type (WT) littermates. MtCK activity was 27% higher than WT, with no change in other CK isoenzymes or creatine levels. Electron microscopy confirmed normal mitochondrial cell density and mitochondrial localization of transgenic protein. Respiration in isolated mitochondria was unaltered and metabolomic analysis by 1 H-NMR suggests that cellular metabolism was not grossly affected by transgene expression. There were no significant differences in cardiac structure or function under baseline conditions by cine-MRI or LV haemodynamics. In Langendorff-perfused hearts subjected to 20 min ischaemia and 30 min reperfusion, MtCK-OE exhibited less ischaemic contracture, and improved functional recovery (Rate pressure product 58% above WT; P 

Original publication




Journal article


Cardiovasc Res

Publication Date





858 - 869


Adenosine Triphosphate, Animals, Calcium Signaling, Creatine Kinase, Creatine Kinase, Mitochondrial Form, Disease Models, Animal, Female, Isolated Heart Preparation, Magnetic Resonance Imaging, Cine, Male, Metabolomics, Mice, Inbred C57BL, Mice, Transgenic, Microscopy, Electron, Transmission, Mitochondria, Heart, Mitochondrial Membrane Transport Proteins, Mitochondrial Permeability Transition Pore, Myocardial Contraction, Myocardial Reperfusion Injury, Myocytes, Cardiac, Oxidative Phosphorylation, Phosphocreatine, Proton Magnetic Resonance Spectroscopy, Recovery of Function, Time Factors, Up-Regulation, Ventricular Function, Left