EFFECT OF THE 21-AMINOSTEROID TIRILAZAD ON CEREBRAL PH AND SOMATOSENSORY EVOKED-POTENTIALS AFTER INCOMPLETE ISCHEMIA

Background and Purpose: Postischemic evoked potential recovery correla tes with acidosis during ischemia and early reperfusion. Acidosis prom otes lipid peroxidation in vitro. We tested the hypothesis that the 21 -aminosteroid tirilazad mesylate (U74006F), an inhibitor of lipid pero xidation in vitro, ameliorates somatosensory evoked potential recovery and acidosis during reperfusion after severe incomplete cerebral isch emia. Methods: Cerebral perfusion pressure was reduced to 11+/-1 mm Hg (+/-SEM) for 30 minutes by cerebral ventricular fluid infusion in ane sthetized dogs. Cerebral intracellular pH and high-energy phosphates w ere measured by magnetic resonance spectroscopy. Dogs were randomized to receive vehicle (citrate buffer, n=8) or tirilazad (1 mg/kg; n=8) b efore ischemia in a blinded study. Results: Cerebral blood flow was re duced to 6+/-1 mL/min per 100 g during ischemia, resulting in nearly c omplete loss of high-energy phosphates and an intracellular pH of 6.0- 6.1 in both groups. Initial postischemic hyperemia was similar between groups but lasted longer in the vehicle group. Tirilazad accelerated mean recovery time of intracellular pH from 31+/-5 to 15+/-3 minutes a nd of inorganic phosphate from 13+/-2 to 6+/-1 minutes. Recovery of so matosensory evoked potential amplitude was greater with tirilazad (49/-3%) than vehicle (33+/-6%). Fractional cortical water content was le ss with tirilazad (0.819+/-0.003) than vehicle (0.831+/-0.002). Conclu sions. Tirilazad attenuates cerebral edema and improves somatosensory evoked potential recovery after incomplete ischemia associated with se vere acidosis. Accelerated pH and inorganic phosphate recovery indicat es that this antioxidant acts during the early minutes of reperfusion.