Ischaemic and morphine-induced post-conditioning: impact of mK(Ca) channels

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Abstract

Mitochondrial calcium-sensitive potassium (mK(Ca)) channels are involved in cardiac preconditioning. In the present study, we investigated whether also ischaemic-, morphine-induced post-conditioning, or both is mediated by the activation of mK(Ca) channels in the rat heart in vitro. Animals were treated in compliance with institutional and national guidelines. Male Wistar rats were randomly assigned to one of seven groups (each n=7). Control animals were not further treated. Post-conditioning was induced either by 3x30 s of ischaemia/reperfusion (I-PostC) or by administration of morphine (M-PostC, 1 mu M) for 15 min at the onset of reperfusion. The mK(Ca)-channel inhibitor paxilline (1 mu M) was given with and without post-conditioning interventions (M-PostC+Pax, I-PostC+Pax, and Pax). As a positive control, we determined whether direct activation of mK(Ca) channels with NS1619 (10 mu M) induced cardiac post-conditioning (NS1619). Isolated hearts underwent 35 min ischaemia followed by 120 min reperfusion. At the end of reperfusion, infarct sizes were measured by triphenyltetrazolium chloride staining. In the control group, infarct size was 53 (5)% of the area at risk. Morphine- and ischaemic post-conditioning reduced infarct size in the same range [M-PostC: 37 (4)%, I-PostC: 35 (5)%; each P <0.05 vs control]. The mK(Ca)-channel inhibitor paxilline completely blocked post-conditioning [M-PostC+Pax: 47 (7)%, I-PostC+Pax: 51 (3)%; each P <0.05 vs M-PostC and I-PostC, respectively]. Paxilline itself had no effect on infarct size (NS vs control). NS1619 reduced infarct size to 33 (4)% (P <0.05 vs control). Ischaemic- and morphine-induced post-conditioning is mediated by the activation of mK(Ca) channels
Original languageEnglish
Pages (from-to)589-595
JournalBritish Journal of Anaesthesia
Volume105
Issue number5
DOIs
Publication statusPublished - 2010

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