Mohan C, Marini C, Gennaro M, Ascer E
Division of Vascular Surgery, Maimonides Medical Center, Brooklyn, NY 11219.
J Vasc Surg. 1992 Aug;16(2):268-73.
Iloprost has been shown to minimize skeletal muscle necrosis when administered before the onset of ischemia in animal experiments, possibly by preventing neutrophil activation. Since patients with acute limb ischemia are seen after the process has begun, we investigated whether iloprost can be protective when given only during reperfusion. After anesthesia, 18 adult mongrel dogs underwent a standard isolated gracilis muscle preparation. In six control animals (group I) the gracilis muscle was subjected to 6 hours of ischemia followed by 48 hours of reperfusion. Group II animals (n = 6) received intravenous infusion of iloprost at a dose of 0.45 microgram/kg/hr beginning 1 hour before the onset of muscle ischemia and throughout the experiment (6 hours of ischemia and 1 hour of reperfusion). In addition to the continuous infusion, they received 0.45 microgram/kg intravenous boluses of iloprost 10 minutes before the induction of ischemia and 10 minutes before reperfusion. Group III animals (n = 6) had a similar ischemic interval, but were given a bolus of iloprost of 0.45 microgram/kg at end ischemia followed by continuous infusion of 0.45 microgram/kg/hr for 48 hours during reperfusion. Muscle biopsies were obtained at baseline and after 1 hour of reperfusion in all groups. Additional biopsies were obtained at 48 hours of reperfusion in groups I and III. Myeloperoxidase activity, a marker of neutrophil activation, was measured in all muscle biopsies. At the end of reperfusion, the gracilis muscle was harvested in all animals and weighed. Muscle necrosis was estimated by serial transection, nitroblue tetrazolium histochemical staining followed by computerized planimetry.(ABSTRACT TRUNCATED AT 250 WORDS)
在动物实验中,已表明依洛前列素在缺血发作前给药时可使骨骼肌坏死降至最低,这可能是通过防止中性粒细胞活化实现的。由于急性肢体缺血患者是在发病过程开始后才被发现,我们研究了依洛前列素仅在再灌注期间给药时是否具有保护作用。麻醉后,18只成年杂种犬接受标准的股薄肌分离制备。6只对照动物(I组)的股薄肌经历6小时缺血,随后再灌注48小时。II组动物(n = 6)在肌肉缺血发作前1小时开始并在整个实验过程中(6小时缺血和1小时再灌注)以0.45微克/千克/小时的剂量静脉输注依洛前列素。除持续输注外,它们在缺血诱导前10分钟和再灌注前10分钟接受0.45微克/千克的依洛前列素静脉推注。III组动物(n = 6)有相似的缺血间期,但在缺血结束时给予0.45微克/千克的依洛前列素推注,随后在再灌注期间以0.45微克/千克/小时的速度持续输注48小时。在所有组的基线和再灌注1小时后获取肌肉活检样本。I组和III组在再灌注48小时时获取额外的活检样本。在所有肌肉活检样本中测量中性粒细胞活化标志物髓过氧化物酶活性。再灌注结束时,在所有动物中收获股薄肌并称重。通过连续横切、硝基蓝四氮唑组织化学染色,然后进行计算机化平面测量来估计肌肉坏死情况。(摘要截取自250字)