Lefer A M, Lefer D J
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Cardiovasc Res. 1996 Oct;32(4):743-51.
The microcirculation undergoes a profound degree of endothelial dysfunction within minutes (i.e., 2.5 to 5 min) following reperfusion of ischaemic vasculature. This has been documented in the coronary and mesenteric microcirculation. The endothelial dysfunction is characterized by a loss in basal and agonist-mediated nitric oxide (NO) produced by the vascular endothelium. The loss of NO results in upregulation of cell adhesion molecules (CAMs) particularly P-selectin 10-20 min following reperfusion. Thus, CAM upregulation renders the endothelium sticky, and a marked degree of leukocyte adherence (particularly neutrophils) occurs 20 min following reperfusion. This enhanced involvement of neutrophils leads to neutrophil infiltration into the underlying tissue (e.g., myocardium) within 2-3 h of reperfusion. The infiltration of neutrophils leads to reperfusion injury (i.e., necrosis) which is significant at 3 h but becomes profound at 4.5 h following reperfusion. Cardiac necrosis can be significantly attenuated by treatment with NO, an organic NO donor, L-arginine, or specific blockers of CAMs given just prior to reperfusion. This approach is a promising one for a variety of types of reperfusion injury.
在缺血性血管再灌注后的数分钟内（即2.5至5分钟），微循环会出现严重程度的内皮功能障碍。这已在冠状动脉和肠系膜微循环中得到证实。内皮功能障碍的特征是血管内皮产生的基础一氧化氮（NO）和激动剂介导的NO减少。NO的减少导致细胞粘附分子（CAMs）上调，尤其是在再灌注后10 - 20分钟时P - 选择素上调。因此，CAMs上调使内皮具有粘性，在再灌注后20分钟会出现显著程度的白细胞粘附（尤其是中性粒细胞）。中性粒细胞的这种增加的参与导致在再灌注后2 - 3小时内中性粒细胞浸润到下层组织（如心肌）中。中性粒细胞的浸润导致再灌注损伤（即坏死），在再灌注后3小时较为显著，但在4.5小时时变得严重。在再灌注前给予NO、有机NO供体、L - 精氨酸或CAMs的特异性阻滞剂进行治疗，可显著减轻心脏坏死。这种方法对于各种类型的再灌注损伤来说是一种很有前景的方法。
