Loukogeorgakis Stavros P, Panagiotidou Anna T, Yellon Derek M, Deanfield John E, MacAllister Raymond J
Vascular Physiology Unit, Institute of Child Health, University College London, London, WC1N 3JE, United Kingdom.
Circulation. 2006 Feb 21;113(7):1015-9. doi: 10.1161/CIRCULATIONAHA.105.590398. Epub 2006 Feb 13.
Hypoxic cell death follows interruption of blood supply to tissues. Although successful restoration of blood flow is mandatory for salvage of ischemic tissues, reperfusion can paradoxically place tissues at risk of further injury. Brief periods of ischemia applied at the onset of reperfusion have been shown to reduce ischemia-reperfusion (IR) injury, a phenomenon called postconditioning. The aim of this study was to determine whether postconditioning protects against endothelial IR injury in humans, in vivo.
Brachial artery endothelial function was assessed by vascular ultrasound to measure flow-mediated dilation (FMD) in response to forearm reactive hyperemia. FMD was measured before and after IR (20 minutes of arm ischemia followed by 20 minutes of reperfusion) in healthy volunteers. To test the protective effects of postconditioning, 3 cycles of reperfusion followed by ischemia (each lasting 10 or 30 seconds) were applied immediately after 20 minutes of arm ischemia. To determine whether postconditioning needs to be applied at the onset of reperfusion, a 1-minute period of arm reperfusion was allowed before the application of the 10-second postconditioning stimulus. IR caused endothelial dysfunction (FMD 9.1+/-1.2% pre-IR, 3.6+/-0.7% post-IR, P<0.001; n=11), which was prevented by postconditioning applied as 10-second cycles of reperfusion/ischemia (FMD 9.9+/-1.7% pre-IR, 8.3+/-1.4% post-IR, P=NS; n=11) and 30-second cycles of reperfusion/ischemia (FMD 10.8+/-1.7% pre-IR, 9.5+/-1.5% post-IR, P=NS; n=10) immediately at the onset of reperfusion. No protection was observed when the application of the 10-second postconditioning stimulus was delayed for 1 minute after the onset of reperfusion (FMD 9.8+/-1.2% pre-IR, 4.0+/-0.9% post-IR, P<0.001; n=8).
This study demonstrates for the first time that postconditioning can protect against endothelial IR injury in humans. Postconditioning might reduce tissue injury when applied at the onset of reperfusion by modifying the reperfusion phase of IR.
缺氧性细胞死亡发生在组织血液供应中断之后。尽管成功恢复血流对于挽救缺血组织至关重要，但再灌注反而会使组织面临进一步损伤的风险。已表明在再灌注开始时施加短暂的缺血期可减少缺血 - 再灌注（IR）损伤，这一现象称为后适应。本研究的目的是确定后适应在人体体内是否能预防内皮细胞IR损伤。
通过血管超声评估肱动脉内皮功能，以测量对前臂反应性充血的血流介导的血管舒张（FMD）。在健康志愿者中，在IR（手臂缺血20分钟后再灌注20分钟）前后测量FMD。为测试后适应的保护作用，在手臂缺血20分钟后立即施加3个再灌注后缺血周期（每个周期持续10或30秒）。为确定后适应是否需要在再灌注开始时应用，在施加10秒后适应刺激前允许手臂再灌注1分钟时间。IR导致内皮功能障碍（IR前FMD为9.1±1.2%，IR后为3.6±0.7%，P<0.001；n = 11），而在再灌注开始时以10秒的再灌注/缺血周期进行后适应可预防这种情况（IR前FMD为9.9±1.7%，IR后为8.3±1.4%，P = 无显著差异；n = 11）以及以30秒的再灌注/缺血周期进行后适应（IR前FMD为10.8±1.7%，IR后为9.5±1.5%，P = 无显著差异；n = 10）。当10秒后适应刺激在再灌注开始后延迟1分钟施加时，未观察到保护作用（IR前FMD为9.8±1.2%，IR后为4.0±0.9%，P<0.001；n = 8）。
本研究首次证明后适应可预防人体内皮细胞IR损伤。后适应在再灌注开始时应用可能通过改变IR的再灌注阶段来减少组织损伤。
