Dyess D L, Collins J N, Ardell J L, Townsley M I, Taylor A E, Ferrara J J
Department of Surgery, University of South Alabama, Mobile 36693, USA.
J Burn Care Rehabil. 2000 Sep-Oct;21(5):406-13. doi: 10.1097/00004630-200021050-00003.
Burn injuries initiate lipid peroxidation in capillary endothelial cells and cause alterations in microvascular permeability, with subsequent leakage of fluid and protein from the plasma into the interstitium. We evaluated the effects of two lazaroid compounds (U74389F and U75412E) on alterations in microvascular permeability that resulted from burn injuries. A canine model was used for the evaluation of microvascular permeability at the site of the burn injury with the use of a measure of the reflection coefficient (sigma(d)). Hindpaw lymph flow, lymph and plasma total protein concentrations, and arterial, venous, and capillary pressures were measured before burn injuries and for 6 hours in 6 different groups. Footpaw weight gain was then calculated as the percentage of increase of experimental hindpaw relative to the contralateral paw. The damage was attenuated by 20 mg/kg of lazaroid U75412E given before the injuries, but a lower dose was not effective. This agent was also effective in limiting edema formation, as evidenced by changes in footpaw weight gain. However, the administration of either lazaroid compound produced no significant effect on the burn-induced changes in capillary permeability. We conclude that these lazaroids do not prevent burn-induced changes in permeability at the site of injury when administered after an injury. U75412E administered before the injury was effective in limiting the alterations in microvascular permeability.
烧伤会引发毛细血管内皮细胞的脂质过氧化，并导致微血管通透性改变，随后血浆中的液体和蛋白质会渗漏到间质中。我们评估了两种拉扎罗类化合物（U74389F和U75412E）对烧伤引起的微血管通透性改变的影响。使用犬类模型，通过测量反射系数（sigma(d)）来评估烧伤部位的微血管通透性。在烧伤前及之后的6小时内，对6个不同组别的后肢淋巴流量、淋巴和血浆总蛋白浓度以及动脉、静脉和毛细血管压力进行了测量。然后计算足爪重量增加量，即实验后肢相对于对侧后肢增加的百分比。在受伤前给予20mg/kg的拉扎罗类化合物U75412E可减轻损伤，但较低剂量无效。该药物在限制水肿形成方面也有效，这通过足爪重量增加量的变化得以证明。然而，给予任何一种拉扎罗类化合物对烧伤诱导的毛细血管通透性变化均无显著影响。我们得出结论，这些拉扎罗类化合物在损伤后给药时不能预防损伤部位烧伤诱导的通透性变化。在损伤前给予U75412E可有效限制微血管通透性的改变。
