Immature hearts respond metabolically different to remote ischemic preconditioning than mature hearts: A tracer study

  • Dr Nicolaj Støttrup, Department of Cardiology, Aarhus University Hospital Skejby, Denmark
  • Dr Michael Schmidt, Department of Cardiology, Aarhus University Hospital Skejby, Denmark
  • Marie Michelsen, Department of Cardiology, Aarhus University Hospital Skejby, Denmark
  • Dr Keld Sørensen, Department of Cardiology, Aarhus University Hospital Skejby, Denmark
  • Dr Torsten Nielsen, Department of Cardiology, Aarhus University Hospital Skejby, Denmark
  • Dr Hans Erik Bøtker, Department of Cardiology, Aarhus University Hospital Skejby, Denmark
  • Dr Raj Kharbanda, John Radcliffe Hospital, Oxford, United Kingdom
  • Dr Andrew Redington, The Hospital for Sick Children, Toronto, Canada
  • Background: Carbohydrates constitute the dominant energy substrate in the immature and hypoxic mature heart. The effects of remote ischemic preconditioning (rIPC) on myocardial metabolism during ischemia and reperfusion are not fully understood. Dialyzed plasma from mature rabbits undergoing rIPC protects isolated mature rabbit hearts in a Langendorff-model. Objectives: To characterize differences between adult and neonatal response to different rIPC stimuli on glucose metabolism.
    Methods: 21 newborn (1-4 days old) and 24 adult rabbits (3 kg.) were randomized into 3 groups: control, in-vivo rIPC and adult dialysate group. Hearts were mounted in a Langendorff-model and perfused for 55 min stabilization, 40 min global ischemia and 120 min reperfusion. Plasma from the remotely preconditioned adult rabbits was dialyzed, added to the buffer and administrated to the dialysate groups. Glycolytic flux was traced using 5-3H-labled glucose.
    Results: Baseline exogenous glycolytic flux was 2.6 times higher in immature (3.77±0.41 µmol × min-l× g dry wt-1) compared to mature hearts (1.43±0.17 µmol × min-l× g dry wt-1; P=0.0001). During early reperfusion, mature hearts decreased glycolytic flux in rIPC (5.35±0.77; P=0.01) and dialysate groups (6.18±1.3; P=0.05) compared to controls (11.067±1.37 µmol × min-l× g dry wt-1). No significant changes were observed in immature hearts. Lactate release during early reperfusion was reduced in mature rIPC and dialysate (48.78 and 53.80 %, p<0.05) when compared to controls. No differences were observed in the immature groups.
    Conclusion: rIPC modulates adult glucose metabolism by inhibition of glycolytic flux during ischemia and early reperfusion. Immature hearts are incapable of this regulation.