Additive protective effects of late and early ischaemic preconditioning are mediated by the opening of K ATP channels in vivo

. We investigated whether a combination of ischaemic late preconditioning (LPC) and ischaemic early preconditioning (EPC) induces additive myocardial protection in vivo, and the role of ATP-sensitive K (K ATP ) channels in ischaemic LPC and in LPC+EPC. Sixty rabbits were divided into seven groups. Anaesthetized animals were subjected to 30 min of coronary artery occlusion and 120 min of reperfusion (I/R). Controls (CON, n =9) were not preconditioned. LPC ( n =10) was induced in conscious rabbits by a 5-min period of myocardial ischaemia 24 h before I/R. The K ATP channel blocker 5-hydroxydecanoate (5-HD, 5 mg/kg) was given 10 min before I/R with (LPC+5-HD, n =9) or without LPC (5-HD, n =8). EPC ( n =8) was induced by a 5-min period of myocardial ischaemia 10 min before I/R. Animals received LPC and EPC without (LPC+EPC, n =8) or with 5-HD (LPC+EPC+5-HD, n =8). LPC reduced infarct size (IS, triphenyltetrazolium staining) from 57±11% (MW±SD, CON) of the area at risk to 31±19% (LPC, P =0.004). 5-HD did not affect IS (5-HD: 60±12%, P =0.002 versus LPC), but abolished the cardioprotective effects of LPC (LPC+5-HD: 62±18%, P =0.001 versus LPC). EPC reduced IS to 18±8%. Additional LPC led to a further reduction to 8±4% (LPC+EPC, n =8; P =0.005 versus EPC; P =0.004 versus LPC). 5-HD abolished this additional cardioprotective effect of LPC+EPC (LPC+EPC+5-HD, n =8; 46±11%, P ≤0.001 versus LPC+EPC). We conclude that the combination of ischaemic LPC and EPC induces additive cardioprotection. K ATP channel opening mediates the cardioprotective effects of ischaemic LPC and LPC+EPC.