Efficacy and safety of combined alpha-amino-3-hydroxy-5-methyl-4-isoxazole
propionate receptor blockade and
thrombolytic therapy with human recombinant
tissue plasminogen activator (TPA) was tested in a rat
embolic stroke model. Sixty-three rats were embolized in the right internal carotid territory with a 200 microliters
suspension of microclots formed by alternate moving of 150 microliters whole blood and 50 microliters of
thrombin between two interconnected syringes for 4 min. Sixteen embolized rats served as controls, and 16 rats were treated with
NBQX immediately after embolization. Thirty-one rats were treated with TPA 2 h following embolization, and in 16 of these rats additional
NBQX treatments were initiated 90 min following embolization. Hemispheric cerebral blood flow (CBF) was measured by an intraarterial 133Xenon injection method before and after embolization. Carotid angiography displayed the rate of occlusion of the cerebral arterial supply before and
after treatment. Brains were fixed after 2 days, evaluated neuropathologically, and
infarct volumes were measured. Median CBF was reduced by 70-77% in the affected hemispheres following embolization. Significant recanalization occurred in all groups except those treated with
NBQX. TPA-treated rats had significantly better reperfusion compared to controls judged by angiography 3 h following embolization (P = 0.04).
NBQX alone and TPA alone caused insignificant reduction in
infarct volume but, when combined, total
infarct volume was reduced by 77% compared to controls (P = 0.02). Separate measurement of cortical
infarct revealed significantly smaller
infarcts (P = 0.05) in the combined treatment group compared to the TPA treatment group.(ABSTRACT TRUNCATED AT 250 WORDS)