Wolfárd Antal, Császár József, Gera László, Petri András, Simonka János Aurél, Balogh Adáa, Boros Mihály
Department of Surgery, University of Szeged, Szent-Györgyi Albert Medical and Pharmeceutical Center, Szeged, Hungary.
Microcirculation. 2002 Dec;9(6):471-6. doi: 10.1038/sj.mn.7800167.
To examine the microcirculatory changes in the rat tibial periosteum after hindlimb ischemia and reperfusion and to evaluate the effects of endothelin-A (ET-A) receptor antagonist therapy in this condition. The healing and functioning of vascularized bone autografts depend mainly on the patency of the microcirculation, and the activation of ET-A receptors may be an important component of the tissue response that occurs during ischemia-reoxygenation injuries.
Wistar rats were subjected to 1 hour of hindlimb ischemia and 3 hours of reperfusion. The periosteal microcirculation was visualized by intravital fluorescence microscopy. The leukocyte rolling and adherence in the postcapillary venules and the functional capillary density of the periosteum were determined. Two separate groups were treated with the selective ET-A receptor antagonist BQ 610 or the novel ET-A receptor antagonist ETR-p1/fl peptide at the onset of reperfusion.
Reperfusion was accompanied by a significant decrease in functional capillary density and by an increase in the primary and secondary leukocyte-endothelial cell interactions. ET-A receptor inhibition reduced the leukocyte rolling and firm adherence and attenuated the decrease in functional capillary density in both treated groups.
ET-1 plays a major role in microvascular dysfunction in the periosteum during reperfusion. The ET-1-ET-A receptor system might be an important target for tissue salvage therapy in transplantation surgery.
研究大鼠后肢缺血再灌注后胫骨骨膜的微循环变化，并评估内皮素A（ET-A）受体拮抗剂治疗在此情况下的效果。带血管蒂自体骨移植的愈合和功能主要取决于微循环的通畅，ET-A受体的激活可能是缺血-再氧合损伤期间发生的组织反应的重要组成部分。
将Wistar大鼠后肢缺血1小时，再灌注3小时。通过活体荧光显微镜观察骨膜微循环。测定毛细血管后微静脉中的白细胞滚动和黏附以及骨膜的功能性毛细血管密度。在再灌注开始时，两个独立的组分别用选择性ET-A受体拮抗剂BQ 610或新型ET-A受体拮抗剂ETR-p1/fl肽进行治疗。
再灌注伴随着功能性毛细血管密度的显著降低以及初次和二次白细胞-内皮细胞相互作用的增加。ET-A受体抑制减少了白细胞滚动和牢固黏附，并减轻了两个治疗组中功能性毛细血管密度的降低。
ET-1在再灌注期间骨膜微血管功能障碍中起主要作用。ET-1-ET-A受体系统可能是移植手术中组织挽救治疗的重要靶点。
