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Ischaemic preconditioning may abolish the protection afforded by ATP-sensitive potassium channel openers in isolated human atrial muscle

Carr, CS; Yellon, DM; (1997) Ischaemic preconditioning may abolish the protection afforded by ATP-sensitive potassium channel openers in isolated human atrial muscle. BASIC RES CARDIOL , 92 (4) 252 - 260.

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Abstract

The ATP-sensitive potassium channel (K-ATP channel) has been implicated in the mechanism underlying ischaemic preconditioning protection. This study based on human atrium compared the protective effects of ischaemic preconditioning with pre-operative nicorandil (a K-ATP channel opener with nitrate actions). We also examined the added effect of ischaemic preconditioning to that of nicorandil on ischaemic protection. The protective effects of other K-ATP channel openers devoid of nitrate actions were also examined.Atrial trabeculae harvested from patients undergoing routine myocardial revascularisation were divided on the basis of whether patients had been ingesting nicorandil orally preoperatively. Trabeculae were superfused with oxygenated Tyrode's solution and following stabilisation underwent 90 minutes simulated ischaemia followed by 120 minutes reoxygenation (n = 6 per group). Atrial trabeculae exposed to nicorandil underwent either no treatment (N), or ischaemic preconditioning (N + PC) using 3 minutes simulated ischaemia and 7 minutes reoxygenation prior to the 90 minutes simulated ischaemia. Similarly trabeculae not exposed to nicorandil underwent either no treatment, controls (C), or ischaemic preconditioning (PC). The experimental endpoint was recovery of contractile function presented as percentage baseline function. Further groups were examined using other K-ATP channels openers with and without ischaemic preconditioning.In the control group, following 120 minutes reoxygentation the recovery of function reached 28.8 +/- 3.5 %. In contrast, exposure to nicorandil alone improved recovery of function (55.5 % +/- 5.3) to a similar extent as PC (55.3 % +/- 2.5) when compared to controls (p < 0.05, ANOVA). The addition of ischaemic preconditioning to nicorandil exposure abolished protection (29.7 % +/- 3.1). Findings were confirmed using the other K-ATP channels openers.Clinically available nicorandil appears to afford ischaemic protection to isolated human atrial muscle. The addition of a short ischaemic episode to nicorandil exposure seems to completely abolish this protection. Although the mechanism underlying this effect remains unknown, we believe that this observation may have clinical implications.

Type:Article
Title:Ischaemic preconditioning may abolish the protection afforded by ATP-sensitive potassium channel openers in isolated human atrial muscle
Keywords:ischaemic preconditioning, K-ATP channel openers, human atrium, pre-operative nicorandil, INFARCT SIZE, NICORANDIL, DOGS, ISCHEMIA, ANGIOPLASTY, CROMAKALIM, MYOCARDIUM, PINACIDIL, BLOCKADE, NITRATE
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science

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