Ischaemic preconditioning reduces myocardial calcium overload in coronary-occluded pig hearts shown by continuous in vivo assessment using microdialysis

Summary During ischaemia, ATP depletion leads to insufficient fuelling for Na+/K+ ATPase, decreased electrochemical potential and increased influx of calcium ions. This study demonstrated a means to assess the effects of ischaemic preconditioning (IP) on the free intracellular Ca2+ pool during prolonged ischaemia. In a porcine myocardial ischaemia model, microdialysis (MD) was used for sampling of metabolic and injury markers in IP and non‐IP (control) groups. 45Ca2+ was delivered in microperfusate locally to ischaemic myocardium, with distribution and uptake assessed by 45Ca2+ recovery in microdialysate. Cardiomyocytes in vitro were exposed to a Ca2+ ionophore and tested for 45Ca2+ uptake. An accentuated myocardial calcium ion influx (observed as an increased microdialysate 45Ca2+ recovery in the extracellular milieu) was noted in control pigs compared with IP pigs during ischaemia. Suspended cardiomyocytes preincubated with a Ca2+ ionophore to increase the intracellular calcium ion pool and subsequently incubated with 45Ca2+, displayed lower 45Ca2+ uptake in cells compared with control cells not exposed to the ionophore, corroborating the idea of a strong relationship between degree of intracellular calcium overload and microdialysate 45Ca2+ recovery. The ischaemic insult was differentially verified by metabolic and injury markers. We introduce an in vivo method for serial assessment of myocardial calcium overload during ischaemia, using a MD technique and 45Ca2+ inclusion. IP leads to relatively less calcium overload as assessed by this new method, and we interpret this to mean that reduction in calcium overload is an important part of the IP protective effect.