Kato T, Bishop A T, Tu Y K, Wood M B
Department of Orthopedics, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
J Bone Joint Surg Am. 1998 Sep;80(9):1341-8. doi: 10.2106/00004623-199809000-00014.
The function of the vascular endothelium after cold storage at 4 degrees Celsius for one, three, five, and seven days was investigated in a canine tibial perfusion model. Function was assessed in terms of changes in perfusion pressure, changes in the concentration of endothelin in the venous effluent from the perfused tibiae, adrenomedullin-induced vascular smooth-muscle relaxation, and norepinephrine-induced pressor responses in the presence of acetylcholine, N(G)-monomethyl-L-arginine acetate (an inhibitor of nitric oxide synthesis), or indomethacin (an inhibitor of prostaglandin synthesis) in phase 1 of the study. In phase 2 of the study, the effect of the infusion of tetraethylammonium (a potassium-channel blocker that inhibits the activity of endothelium-derived hyperpolarized factor) was analyzed. The baseline perfusion pressures increased in a time-dependent manner (p < 0.05). In tibiae that had been stored for one or three days, the production of endothelin-1 was less than one picogram per milliliter, but it markedly increased to a mean (and standard error of the mean) of 8.7 +/- 3.2 and 10.8 +/- 4.3 picograms per milliliter in tibiae that had been stored for five and seven days, respectively (p < 0.05). Acetylcholine attenuated the norepinephrine-induced pressor response in all groups (storage at 4 degrees Celsius for one, three, five, or seven days) compared with the response in the control tibiae (p < 0.05). Perfusion of acetylcholine in the tibiae that had been stored for three days significantly attenuated the pressor response to norepinephrine compared with that in the tibiae that had been stored for five days (p < 0.05). In the presence of N(G)-monomethyl-L-arginine acetate, the norepinephrine-induced pressor response significantly increased only in the tibiae that had been stored for one day (p < 0.05). In the presence of indomethacin, the norepinephrine-induced pressor response significantly decreased in the tibiae that had been stored at 4 degrees Celsius for one, three, or five days (p < 0.05). Infusion of adrenomedullin relaxed vascular smooth muscle in the tibiae that had been stored for one, three, five, or seven days (p < 0.05). In phase 2 of the study, perfusion of tetraethylammonium in the presence of acetylcholine increased the norepinephrine-induced pressor response in the tibiae that had been stored at 4 degrees Celsius for seven days to a mean of 168 +/- 20 per cent, whereas perfusion with acetylcholine alone attenuated the norepinephrine-induced pressor response to a mean of 54.6 +/- 3.7 per cent.
在犬胫骨灌注模型中，研究了4摄氏度冷藏1天、3天、5天和7天后血管内皮的功能。在研究的第一阶段，根据灌注压力的变化、灌注胫骨静脉流出物中内皮素浓度的变化、肾上腺髓质素诱导的血管平滑肌舒张以及在乙酰胆碱、N(G)-单甲基-L-精氨酸乙酸盐（一氧化氮合成抑制剂）或吲哚美辛（前列腺素合成抑制剂）存在下去甲肾上腺素诱导的升压反应来评估功能。在研究的第二阶段，分析了四乙铵（一种抑制内皮衍生超极化因子活性的钾通道阻滞剂）输注的效果。基线灌注压力以时间依赖性方式增加（p<0.05）。在储存1天或3天的胫骨中，内皮素-1的产生低于每毫升1皮克，但在储存5天和7天的胫骨中分别显著增加至平均（及平均标准误）8.7±3.2和10.8±4.3皮克/毫升（p<0.05）。与对照胫骨中的反应相比，乙酰胆碱减弱了所有组（4摄氏度储存1天、3天、5天或7天）中去甲肾上腺素诱导的升压反应（p<0.05）。与储存5天的胫骨相比，在储存3天的胫骨中灌注乙酰胆碱显著减弱了对去甲肾上腺素的升压反应（p<0.05）。在N(G)-单甲基-L-精氨酸乙酸盐存在下，去甲肾上腺素诱导的升压反应仅在储存1天的胫骨中显著增加（p<0.05）。在吲哚美辛存在下，在4摄氏度储存1天、3天或5天的胫骨中，去甲肾上腺素诱导的升压反应显著降低（p<0.05）。肾上腺髓质素的输注使储存1天、3天、5天或7天的胫骨中的血管平滑肌舒张（p<0.05）。在研究的第二阶段，在乙酰胆碱存在下灌注四乙铵使在4摄氏度储存7天的胫骨中去甲肾上腺素诱导的升压反应增加至平均168±20%，而单独灌注乙酰胆碱则将去甲肾上腺素诱导的升压反应减弱至平均54.6±3.7%。
