ABSTRACT
This study reports the protective of systemic nicardipine and intracisternal nicardipine administration in the three-hemorrhage canine model of chronic cerebral vasospasm. Twenty-one dogs were assigned to one of three groups : control, intravenous nicardipine, and intracisternal nicardipine. All animals received a total of 12ml of fresh unheparinized autologous blood via three cisternal injection. Selective vertebral angiograms were obtained before intravenous nicardipine for 7 days continuously, the other seven were treated by intracisternal nicardipine for 7 days, and the remaining were not treated. Animals were sacrificed at day 9. 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 54+/-6% in control dogs, 35+/-4% in dogs with intravenous nicardipine, 32+/-6% in dogs with intracisternal dicardipine(difference significant, t-test, P<0.05). The preventive effects of intracisternal nicardipine was superior to those of intravenous nicardipine. There was a strong trend toward reduction of medial necrosis in the basilar artery in dogs with intravenous and intracisternal group compared to control dogs. All basilar arteries showed structural changes with celectron microscopic examination ; these included medial necrosis, lysosome, initial changes, endothelial cell vacuoles, and adventitial erythrocytes, leukocytes. Intimal proliferation was unusual in all three groups, but reduction of intimal proliferation was found in dogs with treatment, and it was believed that vasospasm in this stage is due to long-standing smooth muscle contraction and not to arterial wall thickening. There was significant reduction of blood clot in intracisternal nicardipine group, which may be due to inhibitory action on platelet aggregation of nicardipine. These investigations support the hypothesis that the presence of clotted blood around the intracranial arteries is the cause of vasospasm.