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

J. Müllenheim, W. Schlack, J. Frässdorf, A. Heinen, B. Preckel, V. Thämer

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Abstract

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 (KATP) 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 KATP 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 <or = 0.001 versus LPC + EPC). We conclude that the combination of ischaemic LPC and EPC induces additive cardioprotection. KATP channel opening mediates the cardioprotective effects of ischaemic LPC and LPC + EPC
Original languageEnglish
Pages (from-to)178-187
JournalPflugers Archiv
Volume442
Issue number2
DOIs
Publication statusPublished - 2001

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