Department of Anesthesiology, Université Catholique de Louvain, Centre Hospitalier Universitaire UCL de Mont-Godinne, Yvoir, Belgium.
J Cardiovasc Pharmacol. 2012 Dec;60(6):553-60. doi: 10.1097/FJC.0b013e31827303fa.
Ischemia-reperfusion disturbs endothelial physiology and generates a proinflammatory state. Animal studies showed that clonidine administered prior hypoxia improves posthypoxic endothelial function. To investigate this effect in human, we have assessed the postischemic endothelium function and the proinflammatory state in healthy volunteers with and without clonidine. Seven volunteers were included. Each subject underwent the experimental protocol (15 minutes nondominant forearm ischemia) with and without clonidine. Endothelial function was assessed by flow-mediated dilatation (FMD) in the brachial artery before ischemia (FMDPI), immediately after ischemia (FMDIAI), and 15 minutes after ischemia (FMD15AI). Neutrophil (CD11b/CD18) and platelet (CD42b) activations were measured by flow cytometry during reperfusion in blood samples from ischemic (local) and nonischemic (systemic) forearms. Proinflammatory state was assessed by serum concentration of interleukin (IL)-1β and -6. Clonidine does not influence baseline FMD (P = 0.118) but improves FMDIAI (P = 0.018) and FMD15AI (P = 0.018). It increases platelet activation in systemic circulation (P = 0.003) during reperfusion but not in local circulation (P = 0.086). Clonidine increases neutrophil activation in local circulation (P = 0.001) but not in systemic circulation (P = 0.642). In local circulation, clonidine decreases IL-6 (P = 0.044) but does not influence IL-1β (P = 0.113). By contrast, it decreases both IL-6 (P = 0.026) and IL-1β (P = 0.027) concentrations in systemic circulation. In conclusion, clonidine improves endothelial function and modulates inflammation during reperfusion.
缺血再灌注会扰乱内皮细胞的生理机能，并产生促炎状态。动物研究表明，在缺氧前给予可乐定可改善缺氧后的内皮功能。为了在人类中研究这种效应，我们评估了有和没有可乐定的健康志愿者的缺血后内皮功能和促炎状态。共纳入 7 名志愿者。每位受试者均接受实验方案（15 分钟非优势前臂缺血），同时有无可乐定。在缺血前（FMDPI）、缺血即刻（FMDIAI）和缺血后 15 分钟（FMD15AI），通过肱动脉血流介导的舒张功能（FMD）评估内皮功能。在缺血（局部）和非缺血（全身）前臂的血液样本中，通过流式细胞术在再灌注期间测量中性粒细胞（CD11b/CD18）和血小板（CD42b）的激活。通过血清白细胞介素（IL）-1β和-6 浓度评估促炎状态。可乐定不影响基线 FMD（P=0.118），但改善 FMDIAI（P=0.018）和 FMD15AI（P=0.018）。它增加再灌注期间全身循环中的血小板激活（P=0.003），但不增加局部循环中的血小板激活（P=0.086）。可乐定增加局部循环中的中性粒细胞激活（P=0.001），但不增加全身循环中的中性粒细胞激活（P=0.642）。在局部循环中，可乐定降低了 IL-6（P=0.044），但不影响 IL-1β（P=0.113）。相比之下，它降低了全身循环中 IL-6（P=0.026）和 IL-1β（P=0.027）的浓度。总之，可乐定在再灌注期间改善内皮功能并调节炎症。
