COMPARISON OF INTRATHECAL ADMINISTRATION OF UROKINASE AND TISSUE-PLASMINOGEN ACTIVATOR ON SUBARACHNOID CLOT AND CHRONIC VASOSPASM IN A PRIMATE MODEL

SAFETY AND EFFICACY of the thrombolytic agent urokinase (URO) in the e limination of subarachnoid clot and prevention of chronic vasospasm wa s compared with tissue-type plasminogen activator (rt-PA) in a blind, randomized placebo-controlled trial. Twenty monkeys were randomly assi gned to one of five groups of four. Each group underwent baseline cere bral angiography followed by bilateral craniectomy and experimental su barachnoid hemorrhage. An Ommaya reservoir was inserted on the right s ide with its catheter placed into the ipsilateral subarachnoid space. Twenty-four hours later, depending upon group assignment, the animals received 100,000 IU URO, 200,000 IU URO, 1 mg rt-PA, 2 mg rt-PA, or th e equivalent volume of normal saline (control group). On Day 7, angiog raphy was repeated and the animals were killed. One animal died as a r esult of complications during the baseline angiography, presumably due to blood loss and prolonged anesthesia, and a replacement animal was obtained. No animals demonstrated any delayed neurological deficits. T he study demonstrated that a single intracisternal bolus injection of rt-PA, 2.0 mg in 2 ml sterile water, or URO, 200,000 IU in 2 ml steril e water, 24 hours after induction of experimental subarachnoid hemorrh age in primates, was equally effective in thrombolysing ipsilateral cl ot, but neither dosage prevented angiographic vasospasm. Vasospasm occ urred bilaterally in all groups. Whereas gross subarachnoid clot was f ound bilaterally in all animals in the placebo group and both smaller- dose URO and rt-PA groups, right-sided subarachnoid clot was virtually absent and left-sided clot reduced in both higher-dose URO and rt-PA groups. Intrathecal URO in the dosage used had no apparent adverse eff ect on the animal's neurological condition or the histological appeara nce of the cerebral cortex, pia, arachnoid, or ependyma. No clear diff erence between rt-PA and URO emerged in this study at the dosages and timing of administration employed. Presumably larger dosages, given ea rlier or more often, would be required to completely lyse the bilatera l clots and prevent vasospasm.