Kharbanda R K, Mortensen U M, White P A, Kristiansen S B, Schmidt M R, Hoschtitzky J A, Vogel M, Sorensen K, Redington A N, MacAllister R
University College, London, UK.
Circulation. 2002 Dec 3;106(23):2881-3. doi: 10.1161/01.cir.0000043806.51912.9b.
Ischemic preconditioning reduces local tissue injury caused by subsequent ischemia-reperfusion (IR), but may also have a salutary effect on IR injury of tissues remote from those undergoing preconditioning. We tested the hypothesis that limb ischemia induces remote preconditioning, reduces endothelial IR injury in humans, and reduces experimental myocardial infarct size.
Endothelial IR injury of the human forearm was induced by 20 minutes of upper limb ischemia (inflation of a blood pressure cuff to 200 mm Hg) followed by reperfusion. Remote preconditioning was induced by three 5-minute cycles of ischemia of the contralateral limb. Venous occlusion plethysmography was used to assess forearm blood flow in response to acetylcholine at baseline and 15 minutes after reperfusion. Experimental myocardial infarction was achieved by 40 minutes of balloon occlusion of the left anterior descending artery in 15-kg pigs. Remote preconditioning was induced by four 5-minute cycles of lower limb ischemia. Triphenyltetrazolium staining was used to assess the extent of myocardial infarction. In the human study, the response to acetylcholine was significantly attenuated in the control group after 15 minutes' reperfusion, but remote preconditioning prevented this reduction. Limb ischemia caused a significant reduction in the extent of myocardial infarction relative to the area at risk compared with control (26+/-9% versus 53+/-8%, P<0.05).
Remote ischemic preconditioning prevents IR-induced endothelial dysfunction in humans and reduces the extent of myocardial infarction in experimental animals. Transient limb ischemia is a simple preconditioning stimulus with important potential clinical applications.
缺血预处理可减轻随后的缺血-再灌注（IR）所导致的局部组织损伤，但对远离预处理部位的组织的IR损伤可能也有有益作用。我们检验了以下假设：肢体缺血可诱导远隔预处理，减轻人类内皮细胞IR损伤，并减小实验性心肌梗死面积。
通过使上肢缺血20分钟（将血压袖带充气至200 mmHg）然后再灌注，诱导人前臂的内皮细胞IR损伤。通过对侧肢体3个5分钟的缺血周期诱导远隔预处理。在基线以及再灌注后15分钟，使用静脉阻塞体积描记法评估前臂对乙酰胆碱的血流反应。通过对15 kg猪的左前降支进行40分钟的球囊闭塞来造成实验性心肌梗死。通过下肢4个5分钟的缺血周期诱导远隔预处理。使用三苯基四氮唑染色评估心肌梗死范围。在人体研究中，对照组在再灌注15分钟后对乙酰胆碱的反应显著减弱，但远隔预处理可防止这种减弱。与对照组相比，肢体缺血导致心肌梗死范围相对于危险区域显著减小（26±9% 对53±8%，P<0.05）。
远隔缺血预处理可防止人类IR诱导的内皮功能障碍，并减小实验动物的心肌梗死范围。短暂肢体缺血是一种具有重要潜在临床应用价值的简单预处理刺激。
