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 (LP C) and ischaemic early preconditioning (EPC) induces additive myocardial pr otection in vivo, and the role of ATP-sensitive K (K-ATP) channels in ischa emic LPC and in LPC+EPC. Sixty rabbits were divided into seven groups. Anae sthetized 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 myocardia l ischaemia 24 h before I/R. The K, channel blocker 5-hydroxydecanoate (5-H D, 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 ischaem ia IO min before VR. Animals received LPC and EPC without (LPC+EPC, n=8) or with 5-HD (LPC+EPC+5-HD, n=8). LPC reduced infarct size CIS, triphenyltetr azolium staining) from 57 +/- 11% (MW +/- SD, CON) of the area at risk to 3 1 +/- 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 less than or equal to0.001 ver sus LPC+EPC). We conclude that the combination of ischaemic LPC and EPC ind uces additive cardioprotection. K, channel opening mediates the cardioprote ctive effects of ischaemic LPC and LPC+EPC.