Faculty Collaboration Database

Effect of the 21-aminosteroid tirilazad on cerebral pH and somatosensory evoked potentials after incomplete ischemia. Stroke 1993 May;24(5):724-30

Date

05/01/1993

Pubmed ID

8488529

DOI

10.1161/01.str.24.5.724

Scopus ID

2-s2.0-0027243338 (requires institutional sign-in at Scopus site)   31 Citations

Abstract

BACKGROUND AND PURPOSE: Postischemic evoked potential recovery correlates with acidosis during ischemia and early reperfusion. Acidosis promotes lipid peroxidation in vitro. We tested the hypothesis that the 21-aminosteroid tirilazad mesylate (U74006F), an inhibitor of lipid peroxidation in vitro, ameliorates somatosensory evoked potential recovery and acidosis during reperfusion after severe incomplete cerebral ischemia.

METHODS: Cerebral perfusion pressure was reduced to 11 +/- 1 mm Hg (+/- SEM) for 30 minutes by cerebral ventricular fluid infusion in anesthetized dogs. Cerebral intracellular pH and high-energy phosphates were measured by magnetic resonance spectroscopy. Dogs were randomized to receive vehicle (citrate buffer; n = 8) or tirilazad (1 mg/kg; n = 8) before ischemia in a blinded study.

RESULTS: Cerebral blood flow was reduced to 6 +/- 1 mL/min per 100 g during ischemia, resulting in nearly complete 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 and of inorganic phosphate from 13 +/- 2 to 6 +/- 1 minutes. Recovery of somatosensory evoked potential amplitude was greater with tirilazad (49 +/- 3%) than vehicle (33 +/- 6%). Fractional cortical water content was less with tirilazad (0.819 +/- 0.003) than vehicle (0.831 +/- 0.002).

CONCLUSIONS: Tirilazad attenuates cerebral edema and improves somatosensory evoked potential recovery after incomplete ischemia associated with severe acidosis. Accelerated pH and inorganic phosphate recovery indicates that this antioxidant acts during the early minutes of reperfusion.

Author List

Maruki Y, Koehler RC, Kirsch JR, Blizzard KK, Traystman RJ

MESH terms used to index this publication - Major topics in bold

Acidosis
Adenosine Triphosphate
Animals
Bicarbonates
Brain
Brain Edema
Brain Ischemia
Cytoplasm
Dogs
Drug Evaluation, Preclinical
Evoked Potentials, Somatosensory
Hydrogen-Ion Concentration
Male
Phosphocreatine
Pregnatrienes
Reactive Oxygen Species
Reperfusion Injury