Effects of heparin-urokinase on the brain damage induced by complete global brain ischemia

The effect of heparin-urokinase (H-U) on the prevention of brain damage induced by ischemia was evaluated in 31 dogs subjected to an 18 min of complete global brain ischemia. Complete brain ischemia was produced by clamping the ascending aorta with aorto-atrial and aorto-femoral bypass formation. Post-ischemic cerebral blood flow (CBF) and other hemodynamic parameters were measured for 7 hours after ischemia in 15 dogs (acute study). Neurologic outcome was evaluated for 7 days after ischemia in 16 dogs (chronic study). Fifteen minutes after restoration of circulation to the brain, an intravenous bolus of heparin 100 I.U./kg and urokinase 3000 I.U./kg, was given, followed by continuous intravenous infusion of heparin 0.25 I.U./kg/min and urokinase 8.3 I.U./kg/min for 6 hours. H-U significantly improved both post-ischemic CBF and neurologic outcome. H-U was effective in treating brain damage when given 15 min after ischemia. These results suggest that H-U improved both post ischemic CBF and neurologic outcome owing to amelioration of the deterioration of microcirculation.

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