Ischemic preconditioning prevents endothelial injury and systemic neutrophil activation during ischemia-reperfusion in humans in vivo
Ischemic preconditioning prevents endothelial injury and systemic neutrophil activation during ischemia-reperfusion in humans in vivo
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DOI：
10.1161/01.cir.103.12.1624
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发表时间：
2001-03-27
期刊：
影响因子：
37.8
通讯作者：
MacAllister, R
中科院分区：
文献类型：
--
作者：
Kharbanda, RK;Peters, M;MacAllister, R
背景-内皮功能障碍导致组织中的中性粒细胞浸润与缺血-再灌注（IR）引起的组织损伤有关。预先缺血预处理（IPC）可减轻IR时的组织损伤。在人类中，尚不清楚IR期间是否发生内皮功能障碍，或者IPC是否提供针对内皮功能障碍和炎性细胞活化的保护。我们研究了实验IR对内皮细胞和中性粒细胞的功能在人体前臂在体内的影响，并检查IPC提供的保护。方法和结果前臂缺血20分钟，通过充气血压袖带到200毫米汞柱。我们评估了管道的内皮功能（桡动脉血流介导的扩张）和阻力血管（对动脉内输注内皮依赖性扩张剂乙酰胆碱的血流反应），IR减少了再灌注15分钟时桡动脉的血流介导的扩张（7.7 +/-1.5%至3.5 +/-0.9%）和再灌注15、30和60分钟时阻力血管对乙酰胆碱的扩张反应，IR没有减少桡动脉对甘油三硝酸酯的扩张反应，仅引起甘油三硝酸酯的少量减少。诱导再灌注60分钟时阻力血管扩张，IR引起循环血液中中性粒细胞CD 11b表达和血小板-中性粒细胞复合物增加。IPC（三个5分钟的缺血发作）前IR防止内皮功能障碍和中性粒细胞activation.Conclusions-A临床相关的缺血再灌注期导致深刻的和持续的内皮功能障碍和系统性中性粒细胞活化。IPC在人体内减弱了这两种作用。
Background-Endothelial dysfunction leading to neutrophil infiltration of tissues has been implicated in tissue injury caused by ischemia-reperfusion (IR). Tissue injury during IR can be reduced by prior ischemic preconditioning (IPC). In humans, it is unclear whether endothelial dysfunction occurs during IR or whether IPC offers protection against endothelial dysfunction and inflammatory cell activation. We studied the effects of experimental IR on endothelial and neutrophil function in the human forearm in vivo and examined the protection afforded by IPC.Method and Results-The forearm was made ischemic for 20 minutes by inflating a blood pressure cuff to 200 mm Hg. We assessed endothelial function of conduit (radial artery flow-mediated dilation) and resistance vessels (blood flow responses to intra-arterial infusion of the endothelium-dependent dilator acetylcholine) in healthy volunteers before and after IR, IR reduced flow-mediated dilation of the radial artery at 15 minutes of reperfusion (7.7 +/-1.5% to 3.5 +/-0.9%) and the dilator response of resistance vessels to acetylcholine at 15, 30, and 60 minutes of reperfusion, IR did not reduce the dilator response of the radial artery to glyceryltrinitrate and only caused a small reduction of glyceryltrinitrate-induced dilation of resistance vessels at 60 minutes of reperfusion, IR caused an increase in neutrophil CD11b expression and platelet-neutrophil complexes in the circulating blood. IPC (three 5-minute episodes of ischemia) before IR prevented endothelial dysfunction and neutrophil activation.Conclusions-A clinically relevant period of ischemia-reperfusion causes profound and sustained endothelial dysfunction and systemic neutrophil activation. IPC attenuates both of these effects in humans.