Objective

The aim of this study was to investigate whether remote ischaemic per-conditioning might protect skeletal muscle during lower limb ischaemia–reperfusion (IR).

Methods

Twenty-three male C57BL/6 mice were randomised into three groups: sham group (n = 7), IR group (unilateral tourniquet induced three hours of ischaemia followed by 24 hours of reperfusion, n = 8), and remote ischaemic per-conditioning group (RIPerC) (three cycles of 10 minute IR episodes on the non-ischaemic contralateral hindlimb, n = 8). Oxygraphy, spectrofluorometry, and electron paramagnetic resonance spectroscopy were performed in order to determine mitochondrial respiratory chain complexes activities, mitochondrial calcium retention capacity (CRC) and reactive oxygen species (ROS) production in skeletal muscle.

Results

IR impaired mitochondrial respiration (3.66 ± 0.98 vs. 7.31 ± 0. 54 μmol/min/g in ischaemic and sham muscles, p = .009 and p = .003 respectively) and tended to impair CRC (2.53 ± 0.32 vs. 3.64 ± 0.66 μmol/mg in ischaemic and sham muscles respectively, p = .066). IR did not modify ROS production (0.082 ± 0.004 vs. 0.070 ± 0.004 μmol/min/mg in ischaemic and sham muscles respectively, p = .74). RIPerC failed to restore mitochondrial respiration (3.82 ± 0.40 vs. 3.66 ± 0.98 μmol/min/g in ischaemic muscles from the RIPerC group and the IR group respectively, p = .45) and CRC (2.76 ± 0.3 vs. 2.53 ± 0.32 μmol/mg in ischaemic muscles from the RIPerC group and the IR group respectively, p = .25). RIPerC even impaired contralateral limb mitochondrial respiration (3.85 ± 0.34 vs. 7.31 ± 0. 54 μmol/min/g in contralateral muscles and sham muscles respectively, –47.3%, p = .009).

Conclusion

RIPerC failed to protect ischaemic muscles and induced deleterious effects on the contralateral non-ischaemic muscles. These data do not support the concept of RIPerC.

中文翻译：

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小鼠下肢缺血再灌注期间远程缺血预适应的有害影响

 客观的

本研究的目的是调查远程缺血预调节是否可以在下肢缺血再灌注（IR）期间保护骨骼肌。

 方法

将 23 只雄性 C57BL/6 小鼠随机分为三组：假手术组 ( n = 7)、IR 组（单侧止血带诱导 3 小时缺血，然后再灌注 24 小时， n = 8）和远程缺血预处理组组 (RIPerC)（非缺血对侧后肢 10 分钟 IR 发作三个周期， n = 8）。进行氧描记法、荧光分光光度法和电子顺磁共振波谱法以确定骨骼肌中线粒体呼吸链复合物活性、线粒体钙保留能力（CRC）和活性氧（ROS）产生。

 结果

IR 损害线粒体呼吸（缺血肌和假肌中为 3.66 ± 0.98与7.31 ± 0. 54 μmol/min/g，分别为p = .009 和p = .003），并倾向于损害 CRC（2.53 ± 0.32与3.64 ±缺血肌肉和假肌肉中分别为 0.66 μmol/mg， p = .066)。 IR 不会改变 ROS 的产生（缺血肌肉和假肌肉中分别为 0.082 ± 0.004 vs. 0.070 ± 0.004 μmol/min/mg， p = .74）。 RIPerC 未能恢复线粒体呼吸（RIPerC 组和 IR 组缺血肌肉中的线粒体呼吸分别为 3.82 ± 0.40与3.66 ± 0.98 μmol/min/g， p = .45）和 CRC（2.76 ± 0.3与2.53 ± 0.32 μmol） RIPerC 组和 IR 组的缺血肌肉中分别为 /mg， p = 0.25）。 RIPerC 甚至损害对侧肢体线粒体呼吸（对侧肌肉和假肌肉分别为 3.85 ± 0.34与7.31 ± 0. 54 μmol/min/g，–47.3%， p = .009）。

 结论

RIPerC 未能保护缺血肌肉，并对对侧非缺血肌肉产生有害影响。这些数据不支持 RIPerC 的概念。