A Study of the Effects of Systemic Heparin and Intrathecal Urokinase on Experimental Cerebral Vasospasm

ABSTRACT

The author has investigated the protective effects of systemic Heparin and intrathecal Urokinase in the multi-hemorrhage canine model of severe chronic cerebral vasospasm. Each of 20 adult mongrel dogs was assigned to one of three experimental groups. All animals received a total of 12ml of fresh unheparinized autologous blood via three cisternal injections. Selective vertebral angiograms were obtained before and 8 days after the initial subarachnoid blood injection. Seven animals were treated by systemic Heparin for 7 days, the other seven were treated by intracisternal Urokinase for 3 days, and the remaining were not treated. Comparisons were based on the percentage of reduction in basilar artery diameter(% RBAD). The ultrastructural changes were studied by transmission electron microscopy(TEM). There was a mean reduction(+/-standard deviation) of 65+/-7% in control dogs, 53+/-5% in dogs with systemic Heparin(difference significant t-test, p<0.01), 37+/-6% in dogs with intrathecal Urokinase(difference signignificant, t-test, p<0.01). The preventive effects of intrathecal Urokinase was superior to systemic Heparin. There was a stroung trend toward reduction of medial necrosis in the basilar artery in dogs with intrathecal Urokinase(p<0.01), and with systemic Heparin(0.05animals. Intimal proliferation was unusual in all three groups, but reduction of intimal proliferation was significant in dogs with treatment. All this morphological changes correlated with degree of angiographic vasospasm. Since chronic severe angiographic vasospasm was present with relatively mild proliferation of the arterial wall, the author believe that vasospasm in this stage is due to long-lasting smooth muscle contraction and not to arterial wall thickening. In preventing vasospasm, it appears that early lysis of subarachnoid blood clot by intrathecal Urokinase has some benefits. And also these observations support the hypothesis that persistence of clotted blood around the intracranial arteries is the cause of the vasospasm.