POSSIBILITIES OF BRAIN PROTECTION WITH TIRILAZAD AFTER CARDIAC-ARREST

Cardiac arrest and resuscitation often create a cerebral insult caused by the initial cessation of blood pow followed by the incomplete isch emia of cardiopulmonary resuscitation (low how), and, following the re turn of spontaneous circulation, by the postresuscitation syndrome. A cascade of physiologic, vascular, and biochemical events is set in mot ion, including changes in neuropeptides, electrolytes such as calcium and magnesium, excitatory neurotransmitters such as glutamate and acet ylcholine, lymphokines such as interleukin-1, and arachidonic acid met abolites such as prostaglandins and leukotrienes; and formation of oxy gen free radicals and lactic acid. Oxygen free radical-induced lipid p eroxidation appears to increase tissue injury during and after brain i schemia. The 21-aminosteroid U74006F (tirilazad mesylate) is a novel i nhibitor of lipid membrane peroxidation induced by oxygen free radical s, which has been shown, in animal models of subarachnoid hemorrhage, central nervous system trauma, and cerebral ischemia, to limit the ext ent of secondary tissue damage, thus improving functional recovery. Si nce tirilazad appears to have little or no behavioral or physiologic s ide effects, it appears to be an ideal agent for widespread brain isch emia prophylaxis. Tirilazad mesylate studies in out-of-hospital cardia c arrest are currently being planned.