Loukogeorgakis Stavros P, Panagiotidou Anna T, Broadhead Michael W, Donald Ann, Deanfield John E, MacAllister Raymond J
Vascular Physiology Unit, Institute of Child Health, University College London, London, United Kingdom.
J Am Coll Cardiol. 2005 Aug 2;46(3):450-6. doi: 10.1016/j.jacc.2005.04.044.
The aim of this study was to characterize the time course and neuronal mechanism of remote ischemic preconditioning (RIPC) of the vasculature in humans.
Non-lethal ischemia of internal organs induces local (ischemic preconditioning) and systemic (RIPC) resistance to lethal ischemia-reperfusion (IR) injury. Experimental RIPC has two temporal components, is neuronally mediated, is induced by limb ischemia, and reduces infarct size. In humans, RIPC prevents IR-induced vascular injury. Determining the time course and mechanism is a prelude to clinical outcome studies of RIPC.
Endothelial IR injury was induced by arm ischemia (20 min) and reperfusion, and measured by flow-mediated dilation. To establish if there are early and late phases, RIPC (three 5-min cycles of ischemia of the contralateral arm) was applied immediately, 4, 24, and 48 h before IR. To determine neuronal involvement, trimetaphan (autonomic ganglion blocker; 1 to 6 mg/min intravenous) was infused during the application of the RIPC stimulus.
Flow-mediated dilation was reduced by IR (8.7 +/- 1.1% before IR, 4.9 +/- 1.2% after IR; p < 0.001), but not when preceded by RIPC (8.0 +/- 0.8% after IR; p = NS); RIPC did not protect after 4 h (4.9 +/- 1.1% after IR; p < 0.001), but protected at 24 (8.7 +/- 1.1% after IR; p = NS) and 48 h (8.8 +/- 1.4% after IR; p = NS). Trimetaphan attenuated early (8.3 +/- 1.1% before IR, 4.2 +/- 0.9% after IR; p < 0.05) and delayed (7.3 +/- 1.0% before IR, 2.3 +/- 0.6% after IR, p < 0.001) RIPC.
Remote ischemic preconditioning in humans has two phases of protection against endothelial IR injury; an early (short) and late (prolonged) phase, both of which are neuronally mediated. The potential for late phase RIPC to provide prolonged protection during clinical IR syndromes merits investigation.
本研究旨在描述人体血管远程缺血预处理（RIPC）的时间进程及神经机制。
内脏器官的非致死性缺血可诱导局部（缺血预处理）和全身（RIPC）对致死性缺血再灌注（IR）损伤的抵抗。实验性RIPC有两个时间成分，由神经介导，由肢体缺血诱导，并可减小梗死面积。在人体中，RIPC可预防IR诱导的血管损伤。确定其时间进程和机制是RIPC临床结局研究的前奏。
通过手臂缺血（20分钟）和再灌注诱导内皮IR损伤，并通过血流介导的血管舒张进行测量。为确定是否存在早期和晚期阶段，在IR前即刻、4小时、24小时和48小时应用RIPC（对侧手臂3个5分钟的缺血周期）。为确定神经参与情况，在应用RIPC刺激期间静脉输注曲美芬（自主神经节阻滞剂；1至6毫克/分钟）。
IR可降低血流介导的血管舒张（IR前8.7±1.1%，IR后4.9±1.2%；p<0.001），但在RIPC预处理后则不会（IR后8.0±0.8%；p=无统计学意义）；RIPC在4小时后无保护作用（IR后4.9±1.1%；p<0.001），但在24小时（IR后8.7±1.1%；p=无统计学意义）和48小时（IR后8.8±1.4%；p=无统计学意义）有保护作用。曲美芬减弱了早期（IR前8.3±1.1%，IR后4.2±0.9%；p<0.05）和延迟（IR前7.3±1.0%，IR后2.3±0.6%，p<0.001）的RIPC作用。
人体中的远程缺血预处理对内皮IR损伤有两个保护阶段；一个早期（短暂）阶段和一个晚期（延长）阶段，两者均由神经介导。晚期RIPC在临床IR综合征期间提供长期保护的潜力值得研究。
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