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 flow, followed by the incomplete ischemia of cardiopulmonary resuscitation (low flow), and, following the return of spontaneous circulation, by the post-resuscitation syndrome. A cascade of physiologic, vascular, and biochemical events is set in motion, including changes in neuropeptides, electrolytes such as calcium and magnesium, excitatory neurotransmitters such as glutamate and acetylcholine, lymphokines such as interleukin-1, and arachidonic acid metabolites such as prostaglandins and leukotrienes; and formation of oxygen free radicals and lactic acid. Oxygen free radical-induced lipid peroxidation appears to increase tissue injury during and after brain ischemia. The 21-aminosteroid U74006F (tirilazad mesylate) is a novel inhibitor of lipid membrane peroxidation induced by oxygen free radicals, which has been shown, in animal models of subarachnoid hemorrhage, central nervous system trauma, and cerebral ischemia, to limit the extent of secondary tissue damage, thus improving functional recovery. Since tirilazad appears to have little or no behavioral or physiologic side effects, it appears to be an ideal agent for widespread brain ischemia prophylaxis. Tirilazad mesylate studies in out-of-hospital cardiac arrest are currently being planned.
Sterz
F
F
Department of Emergency Medicine, New Vienna General Hospital, University Clinics, Austria.
Janata
K
K
Kürkciyan
I
I
Müllner
M
M
Malzer
R
R
Schreiber
W
W
D000975:Antioxidants / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000209:etiology / Q000517:prevention & control*; D016887:Cardiopulmonary Resuscitation; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D006323:Heart Arrest / Q000150:complications* / Q000503:physiopathology; D006801:Humans; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011281:Pregnatrienes / Q000627:therapeutic use*
D000975:Antioxidants; D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D011281:Pregnatrienes; C053355:tirilazad