The efficacy of delayed thrombolysis with recombinant
tissue plasminogen activator was tested in combination with the ischaemic protecting
drug NBQX in an
embolic stroke model. In 113 rats the carotid territory was embolized with a
fibrin-rich clot formed in
polyethylene tube. Hemispheric cerebral blood flow (CBF) was measured by intra-arterial 133Xenon injection method before and after embolization. Two hours after embolization 67 animals were treated with
tissue plasminogen activator 20 mg kg-1, 46 control animals with saline.
NBQX was given to 53 animals, of which 41 animals also received
thrombolytic therapy and 12 were saline controls. Carotid angiography displayed the rate of occlusion of the cerebral arterial supply before and
after treatment. Brains were fixed after two days, evaluated neuropathologically, and
infarct volume was measured. Embolization caused a 60-78% reduction of median CBF. The comparison of post-treatment angiography of thrombolytic treated animals to controls showed significant (p < 0.01) reperfusion in thrombolytic treated animals, while
NBQX alone did not enhance reperfusion.
Thrombolytic therapy significantly reduced the total
infarct volume from 19.5% to 4.5% of embolized hemisphere volume (p = 0.006).
NBQX alone reduced total
infarct volume from 19.5% to 6.5% and cortical
infarct volume from 7.9% to 0.3% (p = 0.03). In thrombolytic treated animals
NBQX reduced total
infarct volume from 4.5% to 2.1%. The more than 50% reduction of total
infarction volume caused by
NBQX was not statistically significant due to the variation of
infarct size in this model. Small haemorrhagic lesions in
infarcts were observed in thrombolytic treated animals. The clinical outcome correlated well with
infarct volume.(ABSTRACT TRUNCATED AT 250 WORDS)