Lefer A M, Araki H, Okamatsu S
Circ Shock. 1981;8(3):273-82.
The role of prostanoids in shock states is complex because beneficial as well as deleterious prostanoids are formed during circulatory shock. Recent attention has focused on free radicals formed in the arachidonic acid cascade. MK-447, a free radical scavenger, at 1-4 mg/kg, was found to prolong survival in traumatic shock and to prevent the plasma appearance of a myocardial depressant factor (MDF) in shock rats. In the isolated cat heart perfused under ischemic conditions (ie, coronary flow less than 0.7 ml/min for 2 hours), MK-447 partially restored contractile performance after reestablishment of normal flow and partially prevented cardiac edema. In combination with the cyclooxygenase inhibitor, meclofenamate, MK-447 dramatically restored mechanical performance, prevented leakage of myocardial creatine kinase activity, and cardiac edema. It appears that MK-447 protects in traumatic shock and in myocardial ischemia by a mechanism related to removal of free radicals formed in arachidonic acid metabolism.
前列腺素类物质在休克状态中的作用很复杂，因为在循环性休克期间会形成有益和有害的前列腺素类物质。最近的关注焦点集中在花生四烯酸级联反应中形成的自由基。自由基清除剂MK-447，剂量为1-4mg/kg，被发现可延长创伤性休克动物的存活时间，并防止休克大鼠血浆中出现心肌抑制因子（MDF）。在缺血条件下（即冠状动脉血流量低于0.7ml/min持续2小时）灌注的离体猫心脏中，MK-447在恢复正常血流后部分恢复了收缩功能，并部分预防了心脏水肿。与环氧化酶抑制剂甲氯芬那酸联合使用时，MK-447显著恢复了机械功能，防止了心肌肌酸激酶活性的泄漏以及心脏水肿。看来MK-447通过与清除花生四烯酸代谢中形成的自由基相关的机制，对创伤性休克和心肌缺血起到保护作用。
