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Updated: May 9, 2026
Model of Ischemia and Reperfusion Injury in Rabbits
Published on: November 3, 2023
Remote ischemic preconditioning impairs ventricular function and increases infarct size after prolonged ischemia in
Michael R Schmidt1, Nicolaj B Støttrup1, Marie M Michelsen1
1Department of Cardiology, Aarhus University Hospital, Skejby, Brendstrupgaardsvej, Aarhus N, Aarhus, Denmark.
Insights
Remote ischemic preconditioning (rIPC) protects adult rabbit hearts but harms newborn rabbit hearts. Dialysate from preconditioned adults also caused adverse effects in neonates, indicating rIPC is not suitable for newborns.
Area of Science:
- Cardiology
- Physiology
- Neonatal Research
Background:
- Remote ischemic preconditioning (rIPC) is a known method to reduce myocardial injury in adults undergoing cardiac surgery.
- The efficacy of rIPC in protecting the neonatal heart against ischemia-reperfusion injury remains largely unexplored.
Purpose of the Study:
- To investigate the protective effects of in vivo rIPC and dialysate from preconditioned adult rabbits on neonatal rabbit hearts.
- To compare the response of adult and neonatal rabbit hearts to rIPC and its associated humoral factors.
Main Methods:
- Isolated adult and neonatal rabbit hearts were subjected to control, in vivo rIPC, or dialysate from preconditioned adults.
- Remote preconditioning involved cycles of lower limb ischemia.
- Left ventricular function, glycolytic flux, and infarct size were assessed after ischemia-reperfusion.
Main Results:
- In adult hearts, rIPC and dialysate attenuated glycolytic flux, improved LV function, and reduced infarct size.
- In neonatal hearts, rIPC and dialysate led to lower glycolytic flux, poorer LV function, and larger infarct sizes compared to controls.
- Baseline LV function was similar across all subgroups within age groups.
Conclusions:
- Remote ischemic preconditioning does not protect newborn rabbit hearts from ischemia-reperfusion injury.
- rIPC and its dialysate may exert deleterious effects on the neonatal heart.
- These findings suggest rIPC is not a suitable strategy for protecting the newborn heart.
Objectives:
Remote ischemic preconditioning (rIPC) reduces myocardial injury in adults and children undergoing cardiac surgery. We compared the effect of rIPC in adult and neonatal rabbits to investigate whether protection against ischemia-reperfusion injury can be achieved in the newborn heart by (1) in vivo rIPC and (2) dialysate from adult rabbits undergoing rIPC.
Methods:
Isolated hearts from newborn and adult rabbits were randomized into 3 subgroups (control, in vivo rIPC, and dialysate obtained from adult, remotely preconditioned rabbits). Remote preconditioning was induced by four 5-minute cycles of lower limb ischemia. Left ventricular (LV) function was assessed using a balloon-tipped catheter, glycolytic flux by tracer kinetics, and infarct size by tetrazolium staining. Isolated hearts underwent stabilization while perfused with standard Krebs-Henseleit buffer (control and in vivo rIPC) or Krebs-Henseleit buffer with added dialysate, followed by global no-flow ischemia and reperfusion.
Results:
Within the age groups, the baseline LV function was similar in all subgroups. In the adult rabbit hearts, rIPC and rIPC dialysate attenuated glycolytic flux and protected against ischemia-reperfusion injury, with better-preserved LV function compared with that of the controls. In contrast, in the neonatal hearts, the glycolytic flux was lower and LV function was better preserved in the controls than in the rIPC and dialysate groups. In the adult hearts, the infarct size was reduced in the rIPC and dialysate groups compared with that in the controls. In the neonatal hearts, the infarct size was smaller in the controls than in the rIPC and dialysate groups.
Conclusions:
Remote ischemic preconditioning does not protect against ischemia-reperfusion injury in isolated newborn rabbit hearts and might even cause deleterious effects. Similar adverse effects were induced by dialysate from remotely preconditioned adult rabbits.
