Beneficial actions of a free radical scavenger in traumatic shock and myocardial ischemia.
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.
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D002084:Butylated Hydroxytoluene / Q000031:analogs & derivatives* / Q000494:pharmacology; D002415:Cats; D003327:Coronary Disease / Q000378:metabolism*; D003402:Creatine Kinase / Q000032:analysis; D005260:Female; D005609:Free Radicals; D066298:In Vitro Techniques; D008247:Lysosomes / Q000187:drug effects; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D011449:Prostaglandin Endoperoxides / Q000096:biosynthesis; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D012774:Shock, Traumatic / Q000188:drug therapy / Q000378:metabolism*
D001095:Arachidonic Acids; D005609:Free Radicals; D011449:Prostaglandin Endoperoxides; D011480:Protease Inhibitors; D002084:Butylated Hydroxytoluene; D008469:Meclofenamic Acid; C013753:2-aminomethyl-4-t-butyl-6-iodophenol; D003402:Creatine Kinase