The effect of tissue plasminogen activator (t-PA) on cerebral vasospasm in canine subarachnoid hemorrhage.

Cerebral vasospasm is a serious complication of subarachnoid hemorrhage following rupture of intracranial aneurysm. It always leads to grave neurological deficit and sometimes causes mortality of the patient. Many neurosurgeons consider it as a result of the presence of subarachnoid blood clot and try to prevent it by evacuating the blood clot immediately after clipping of the ruptured aneurysm during operation at acute stage. A nonmechanical method of clearing blood clot by intrathecal injection of thrombolytic agents has been used in recent years. Tissue plasminogen activator (t-PA) is one of these new drugs. Twenty-two dogs were divided into 4 groups in this study: control group (n = 6), vehicle group (n = 6), 50 micrograms/kg t-PA treated group (n = 5) and 100 micrograms/kg t-PA treated group (n = 5). These dogs were prepared as "double hemorrhage canine model." Vehicle solution or different dosages of t-PA were given twice into the foramen magnum through an anchored catheter after artificial subarachnoid hemorrhage. The results showed that the ratio of diameter of basilar artery measured after treatment to that measured before treatment in each groups were 75 +/- 8%, 72 +/- 4%, 86 +/- 4%, and 87 +/- 4%, respectively. The differences between control group and either 50 micrograms/kg t-PA treated group or 100 micrograms/kg t-PA treated groups were statistically significant (p < 0.05). It is concluded that effective prevention of cerebral vasospasm can be achieved safely by administration of t-PA as low as 50 micrograms/kg for two divided doses to dissolve the subarachnoid blood clot in canine model.