Department of Anaesthesiology, University Hospital Duesseldorf, University Hospital Duesseldorf.
Br J Anaesth. 2010 Nov;105(5):589-95. doi: 10.1093/bja/aeq213. Epub 2010 Aug 6.
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 3 × 30 s of ischaemia/reperfusion (I-PostC) or by administration of morphine (M-PostC, 1 µM) for 15 min at the onset of reperfusion. The mK(Ca)-channel inhibitor paxilline (1 µM) 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 µM) 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.
线粒体钙敏感钾 (mK(Ca)) 通道参与了心脏预适应。在本研究中，我们研究了在体大鼠心脏中，缺血后处理、吗啡后处理或二者联合是否通过 mK(Ca) 通道的激活来实现。
动物实验符合机构和国家指导方针。雄性 Wistar 大鼠被随机分配到七组中的一组（每组 n = 7）。对照组动物不进行进一步处理。后处理通过 3×30s 缺血/再灌注（I-PostC）或在再灌注开始时给予吗啡（M-PostC，1μM）15min 来诱导。给予 mK(Ca) 通道抑制剂巴氯芬（1μM）并进行后处理干预（M-PostC+Pax、I-PostC+Pax 和 Pax）。作为阳性对照，我们通过给予 NS1619（10μM）直接激活 mK(Ca) 通道来确定是否诱导了心脏后处理（NS1619）。分离的心脏经历 35min 缺血，随后 120min 再灌注。再灌注结束时，通过三苯基四氮唑染色测量梗死面积。
在对照组中，梗死面积为危险区的 53（5）%。吗啡和缺血后处理以相同范围减少梗死面积[M-PostC：37（4）%，I-PostC：35（5）%；均 P<0.05 与对照组相比]。mK(Ca) 通道抑制剂巴氯芬完全阻断后处理[M-PostC+Pax：47（7）%，I-PostC+Pax：51（3）%；均 P<0.05 与 M-PostC 和 I-PostC 相比]。巴氯芬本身对梗死面积没有影响（与对照组相比无差异）。NS1619 将梗死面积减少到 33（4）%（与对照组相比 P<0.05）。
缺血后处理和吗啡后处理是通过 mK(Ca) 通道的激活介导的。
