Adverse effects of remote ischemic preconditioning in the immature heart

  • Michael Schmidt, Aarhus University Hospital, Skejby, Denmark, Denmark
  • Nicolaj Støttrup, Aarhus University Hospital, Skejby, Denmark, Denmark
  • Marie Michelsen, Aarhus University Hospital, Skejby, Denmark, Denmark
  • Torsten Nielsen, Aarhus University Hospital, Skejby, Denmark, Denmark
  • Hans Erik Bøtker, Aarhus University Hospital, Skejby, Denmark, Denmark
  • Raj Kharbanda, John Radcliffe Hospital, Oxford, UK, United Kingdom
  • Andrew Redington, Hospital for Sick Children, Toronto, Canada
  • Background: Remote ischemic preconditioning (rIPC) reduces myocardial injury in patients undergoing cardiac surgery. Dialyzed plasma from rabbits undergoing rIPC protects isolated rabbit hearts against ischemia-reperfusion (IR)-injury. However, newborn hearts are known to be resistant to local preconditioning. We investigated whether protection against IR-injury is achieved in the newborn heart by 1) in-vivo rIPC and 2) dialysate from adult rabbits undergoing rIPC.
    Methods: 21 newborn (1-4 days old) rabbits randomized into three groups: control (n=7), in-vivo rIPC (n=7) and adult dialysate group (n=7). Remote preconditioning in adult and newborn rabbits was induced by four 5-minute cycles of lower limb ischemia. Plasma from the remotely preconditioned adult rabbits was dialyzed through a 15kDa membrane. All isolated hearts underwent 55 minutes of stabilization while perfused with either standard Krebs-Henseleit buffer (control and in-vivo rIPC) or buffer with added dialysate, followed by 40 minutes of global no-flow ischemia and 120 minutes of reperfusion. Left ventricular (LV) function was assessed throughout using a balloon-tipped catheter and extent of infarction measured by tetrazolium staining.
    Results: Baseline LV function (LV developed pressure (LVDP)) was similar in all groups. However, at 120 minutes of reperfusion, the reduction in LVDP was less in controls (50.1±22.9%) compared to in-vivo (72.3±13.2%, p=0.03) and dialysate (82.4±13.7%, p=0.01) groups. Infarct size (% of LV) was smaller in controls (58.3±6.5%) than in rIPC (70.0±8.1%, p=0.01) and dialysate (73.4±8.4%, p=0.008) groups.
    Conclusion: Remote ischemic preconditioning worsens IR injury in the immature heart, either when applied in-vivo, or induced by dialysate from remotely preconditioned adult rabbits.