A highly selective ATP-dependent potassium channel opener mimics ischaemic preconditioning protection in isolated human atrium

The K-ATP channel has been implicated in the mechanism of ischaemic preconditioning. We examined the effects of EMS 191095, a highly selective K-ATP channel opener, either alone or with glibenclamide (K-ATP channel blocker), on human atrium. Isolated human atrial trabecula superfused with oxygenated Tyrode's solution and paced at I Hz underwent one of four protocols prior to 90 min hypoxic substrate-free perfusion at 3 Hz (simulated ischaemia), followed by 120 min of reoxygenation with substrate at I Hz (reoxygenation). Preconditioning (PC) consisted of 3 min simulated ischaemia and 7 min reoxygenation. The experimental endpoint was recovery of contractile function, presented as percentage of baseline function. EMS (45.8% +/- 4.4) and PC (50.5% +/- 3.6) produced similar functional recoveries following 120 min reperfusion; significantly different to controls (20.8% +/- 3.5, p<0.05, ANOVA). Glibenclamide abolished the EMS protection (20.8% +/- 4.2). This results suggest that ischaemic preconditioning in humans may occur via a K-ATP channel opening effect.