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(0.05
animals. 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.