Abdul-Ghani Safa, Fleishman Arnold N, Khaliulin Igor, Meloni Marco, Angelini Gianni D, Suleiman M-Saadeh
Bristol Heart Institute, School of Clinical Sciences, Faculty of Medicine & Dentistry, University of Bristol, Bristol, United Kingdom.
Research Institute for Complex Problems of Hygiene and Occupational Diseases, Novokuznetsk Kemerovo Oblast, Russia.
Physiol Rep. 2017 Feb;5(3). doi: 10.14814/phy2.13085.
Cardioprotective efficacy of remote ischemic preconditioning (RIPC) remains controversial. Experimental studies investigating RIPC have largely monitored cardiovascular changes during index ischemia and reperfusion with little work investigating changes during RIPC application. This work aims to identify cardiovascular changes associated with autonomic nervous system (ANS) activity during RIPC and prior to index ischemia. RIPC was induced in anesthetized male C57/Bl6 mice by four cycles of 5 min of hindlimb ischemia using inflated cuff (200 mmHg) followed by 5 min reperfusion. Electrocardiography (ECG) and microcirculatory blood flow in both hindlimbs were recorded throughout RIPC protocol. Heart rate variability (HRV) analysis was performed using ECG data. Hearts extracted at the end of RIPC protocol were used either for measurement of myocardial metabolites using high-performance liquid chromatography or for Langendorff perfusion to monitor function and injury during 30 min index ischemia and 2 h reperfusion. Isolated-perfused hearts from RIPC animals had significantly less infarct size after index ischemia and reperfusion (34 ± 5% vs. 59 ± 7%; mean ± SE < 0.05). RIPC protocol was associated with increased heart rate measured both in ex vivo and in vivo. Frequency ratio of HRV spectra was altered in RIPC compared to control. RIPC was associated with a standard hyperemic response in the cuffed-limb but there was a sustained reduction in blood flow in the uncuffed contralateral limb. RIPC hearts (prior to index ischemia) had significantly lower phosphorylation potential and energy charge compared to the control group. In conclusion, RIPC is associated with changes in ANS activity (heart rate, blood flow, HRV) and mild myocardial ischemic stress that would contribute to cardioprotection.
远程缺血预处理（RIPC）的心脏保护效果仍存在争议。研究RIPC的实验研究主要监测了缺血和再灌注期间的心血管变化，而对RIPC应用期间的变化研究较少。这项工作旨在确定RIPC期间及缺血前与自主神经系统（ANS）活动相关的心血管变化。通过使用充气袖带（200 mmHg）对麻醉的雄性C57/Bl6小鼠后肢进行四个周期的5分钟缺血，随后5分钟再灌注来诱导RIPC。在整个RIPC方案中记录心电图（ECG）和双后肢的微循环血流。使用ECG数据进行心率变异性（HRV）分析。在RIPC方案结束时取出的心脏用于通过高效液相色谱法测量心肌代谢物，或用于Langendorff灌注以监测30分钟缺血和2小时再灌注期间的功能和损伤。RIPC动物的离体灌注心脏在缺血和再灌注后梗死面积明显较小（34±5%对59±7%；平均值±标准误，P<0.05）。RIPC方案与体内外测量的心率增加有关。与对照组相比，RIPC中HRV频谱频率比发生改变。RIPC与袖带肢体的标准充血反应相关，但未袖带对侧肢体的血流持续减少。与对照组相比，RIPC心脏（缺血前）的磷酸化电位和能量电荷明显较低。总之，RIPC与ANS活动（心率、血流、HRV）的变化以及轻度心肌缺血应激有关，这有助于心脏保护。
