BENEFICIAL ACTIONS OF A FREE-RADICAL SCAVENGER IN TRAUMATIC SHOCK AND MYOCARDIAL ISCHEMIA

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  • 1 January 1981
    • journal article
    • research article
    • Vol. 8  (3) , 273-282
Abstract
The role of prostanoids in shock states is complex because beneficial and deleterious prostanoids are formed during circulatory shock. Recent attention has focused on free radicals formed in the arachidonic acid cascade. MK-447 [2-aminomethyl-4-t-butyl-6-iodophenol], a free radical scavenger, at 1-4 mg/kg, prolonged survival in traumatic shock and prevented the plasma appearance of a myocardial depressant factor (MDF) in shock rats. In the isolated cat heart perfused under ischemic conditions (i.e., coronary flow < 0.7 ml/min for 2 h), MK-447 partially restored contractile performance after reestablishment of normal flow and partially prevented cardiac edema. Combined with the cyclooxygenase inhibitor, meclofenamate, MK-447 dramatically restored mechanical performance and prevented leakage of myocardial creatine kinase activity and cardiac edema. MK-447 protects in traumatic shock and in myocardial ischemia by a mechanism related to removal of free radicals formed in arachidonic acid metabolism.