Kaeffer N, Richard V, François A, Lallemand F, Henry J P, Thuillez C
Department of Pharmacology (Groupe Vaisseaux-Coeur-Médicaments, Institut Fédératif de Recherches 23-Peptides, Rouen University Medical School, France.
Am J Physiol. 1996 Sep;271(3 Pt 2):H842-9. doi: 10.1152/ajpheart.1996.271.3.H842.
Experiments were designed to test whether preconditioning protects against chronic endothelial injury after ischemia and reperfusion. Coronary arteries were isolated from rats subjected to sham surgery or 20 min of ischemia followed by 1 h, 1 day, 1 wk, or 1 mo of reperfusion without or with preconditioning. The endothelium-dependent relaxations to acetylcholine (ACh; assessed in vitro) were markedly reduced after ischemia and 1 h of reperfusion (31 +/- 6 vs. 57 +/- 6% in sham; P < 0.01) and did not recover after longer durations of reperfusion (1 mo: 32 +/- 5 vs. 56 +/- 2%; P < 0.01). The impaired response to ACh was restored by preconditioning at all time points (1 h: 53 +/- 6; 1 mo: 65 +/- 4%). After 1 mo, the potency of ACh in preconditioned arteries was also increased compared with that in sham animals. Electron microscopy showed marked endothelial damage after 1 h of reperfusion and signs of regenerated endothelium after 1 mo of reperfusion. Both acute and chronic ultrastructural changes were prevented by preconditioning. Thus preconditioning, in addition to protecting myocardial cells, also protects against chronic reperfusion-induced endothelial injury, both in terms of functional and structural changes.
设计实验以测试预处理是否能预防缺血再灌注后的慢性内皮损伤。从接受假手术或经历20分钟缺血随后分别进行1小时、1天、1周或1个月再灌注（有无预处理）的大鼠中分离冠状动脉。缺血及再灌注1小时后，对乙酰胆碱（ACh；体外评估）的内皮依赖性舒张作用显著降低（假手术组为57±6%，缺血再灌注1小时组为31±6%；P<0.01），且在更长时间的再灌注后未恢复（1个月时：假手术组为56±2%，缺血再灌注1个月组为32±5%；P<0.01）。在所有时间点，预处理均可恢复对ACh受损的反应（1小时时：53±6；1个月时：65±4%）。1个月后，与假手术动物相比，预处理动脉中ACh的效能也有所增加。电子显微镜显示，再灌注1小时后内皮有明显损伤，再灌注1个月后有内皮再生迹象。预处理可预防急性和慢性超微结构变化。因此，预处理除了保护心肌细胞外，在功能和结构变化方面还能预防慢性再灌注诱导的内皮损伤。
