Korthuis R J, Granger D N, Townsley M I, Taylor A E
Circ Res. 1985 Oct;57(4):599-609. doi: 10.1161/01.res.57.4.599.
Previous studies indicate that vascular permeability is increased in skeletal muscle subjected to 4 hours of inflow occlusion. However, the mechanism(s) underlying the increase in permeability are unknown. The aim of this study was to assess the role of oxygen-derived free radicals and histamine as putative mediators of the increased permeability in skeletal muscle subjected to 4 hours of inflow occlusion. The osmotic reflection coefficient for total plasma proteins and isogravimetric capillary pressure were estimated in canine gracilis muscle for the following conditions: control, ischemia, and ischemia plus pretreatment with allopurinol (a xanthine oxidase inhibitor), catalase (a peroxidase that reduces hydrogen peroxide to water and molecular oxygen), superoxide dismutase (a superoxide anion scavenger), dimethyl sulfoxide (a hydroxyl radical scavenger), diphenhydramine (a histamine H1-receptor blocker), or cimetidine (a histamine H2-receptor blocker). Ischemia, followed by reperfusion, significantly reduced the reflection coefficient from 0.94 +/- 0.02 to 0.64 +/- 0.02 and isogravimetric capillary pressure from 13.8 +/- 1.0 mm Hg to 6.9 +/- 0.4 mmHg, indicating a dramatic increase in microvascular permeability. Prior treatment with diphenhydramine or cimetidine did not significantly alter the permeability increase induced by ischemia. However, pretreatment with allopurinol, catalase, superoxide dismutase, or dimethylsulfoxide did significantly attenuate the increase in vascular permeability. The results of this study indicate that oxygen radicals are primarily responsible for the increased vascular permeability produced by ischemia-reperfusion, that the hydroxyl radical may represent the primary damaging radical, and that xanthine oxidase may represent the primary source of oxygen-derived free radicals in ischemic skeletal muscle.
先前的研究表明，在经历4小时血流阻断的骨骼肌中，血管通透性会增加。然而，通透性增加背后的机制尚不清楚。本研究的目的是评估氧衍生自由基和组胺作为经历4小时血流阻断的骨骼肌中通透性增加的假定介质的作用。在犬股薄肌中，针对以下情况估计了总血浆蛋白的渗透反射系数和等重力毛细血管压力：对照、缺血以及缺血加用别嘌呤醇（一种黄嘌呤氧化酶抑制剂）、过氧化氢酶（一种将过氧化氢还原为水和分子氧的过氧化物酶）、超氧化物歧化酶（一种超氧化物阴离子清除剂）、二甲基亚砜（一种羟基自由基清除剂）、苯海拉明（一种组胺H1受体阻滞剂）或西咪替丁（一种组胺H2受体阻滞剂）预处理。缺血后再灌注，显著降低了反射系数，从0.94±0.02降至0.64±0.02，等重力毛细血管压力从13.8±1.0 mmHg降至6.9±0.4 mmHg，表明微血管通透性显著增加。用苯海拉明或西咪替丁预先处理并没有显著改变缺血诱导的通透性增加。然而，用别嘌呤醇、过氧化氢酶、超氧化物歧化酶或二甲基亚砜预先处理确实显著减轻了血管通透性的增加。本研究结果表明，氧自由基是缺血再灌注导致血管通透性增加的主要原因，羟基自由基可能是主要的损伤性自由基，黄嘌呤氧化酶可能是缺血骨骼肌中氧衍生自由基的主要来源。
