Correction of ischaemic brain acidosis with SQ29,548/1-benzylimidazole

Thromboxane A₂ (TXA₂) is a proaggregatory vasoconstrictor that is synthesized and released during reperfusion of ischaemic brain. We administered a TXA₂ receptor antagonist, SQ29,548, and a thromboxane A synthase inhibitor, 1-benzylimidazole (1-Bl), to rats subjected to 30 min of reversible forebrain ischaemia. Cerebral thromboxane B₂ (TXB₂), the stable metabolite of TXA₂, measured after 60 min of reperfusion was 0.37 ± 0.08 ng/mg brain protein in animals treated with SQ29,548/1-Bl compared with 1.20 ± 0.16 in ischaemic controls (p < 0.05). Cerebral pH determined by ³¹P magnetic resonance spectroscopy was higher in treated animals, 7.06 ± 0.04, than in ischaemic controls, 6.5 ± 0.01, after 20 min of reperfusion (p ≤ 0.01). The significant elevation of cerebral pH in treated animals persisted at 30 (7.17 ± 0.05 vs. 6.5 ± 0.01; p ≤ 0.01), 35 (7.17 ± 0.05 vs. 6.44 ± 0.04; p ≤ 0.01), and 40 min of reperfusion (7.06 ± 0.06 vs. 6.37 ± 0.01; p ≤ 0.05). We conclude that SQ29,548/1-Bl reduces thromboxane levels and promotes resolution of tissue acidosis in ischaemic brain. The combination of a TXA₂ receptor antagonist with a thromboxane A synthase inhibitor deserves further study as a potential treatment for acute cerebral infarction.