Efficacy of low-dose tissue-plasminogen activator intracisternal administration for the prevention of cerebral vasospasm after subarachnoid hemorrhage.
ABSTRACT Vasospasm is one of the important factors associated with the functional prognosis after subarachnoid hemorrhage (SAH). Intracisternal administration of thrombolytic agents to dissolve subarachnoid clots may be responsible for bleeding complications. The efficacy and safety of cisternal irrigation therapy using low-dose tissue plasminogen activator were evaluated.
Sixty patients with SAH were treated by surgical clipping, and randomly divided into three groups: 1) the control group (n = 20) treated only with baseline treatment; 2) the intermittent group (n = 20) received intermittent administration of clotlysis agent (tisokinase 960,000 IU); and 3) the continuous group (n = 20) received continuous irrigation using pH-adjusted lactate Ringer's solution containing tisokinase (96 IU/mL) infused at 20 mL/hr for 48 hours. The clearance of subarachnoid clots was measured by laboratory examinations and postoperative computed tomography. Ischemia-related vasospasm was evaluated by neurological status and computed tomography. Neurological outcome was evaluated by the modified Rankin scale at 3 months after onset.
The subarachnoid clot was efficiently and significantly removed without major complication in the intermittent and continuous groups (P < 0.05). The incidence of ischemic lesion in the intermittent group was significantly lower than in the control group (P < 0.05). The intermittent group had significantly better neurological outcome than the control group (P < 0.05).
Cisternal irrigation therapy using low-dose tissue plasminogen activator is effective and safe. Intermittent injection is most effective and may decrease the risk of symptomatic vasospasm in patients with SAH.
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ABSTRACT: Magnesium lithospermate B (MLB), a working extract from Salvia miltiorrhiza, was effective against coronary artery disease, ischemic stroke, and chronic renal disease. This study examined the effect of MLB on endothelin-1/endothelial nitric oxide synthase (eNOS) in a subarachnoid hemorrhage (SAH) animal model. A rodent double-hemorrhage model was employed. Animals were randomly assigned to five groups (sham, SAH only, vehicle, 10 mg/kg/day MLB treatment, and pretreatment groups). A radiolabeled NOS Assay Kit was used to detect eNOS. Serum and cerebrospinal fluid sampling for ET-1 (ELISA) was measured. The basilar arteries (BAs) were garnered and sliced, and their cross-sectional areas were determined. In addition, NOS inhibitor nitro-arginine methyl ester (L-NAME) was employed in the SAH+ MLB treatment groups. Significant vasoconstriction was perceived in the SAH group (lumen patency: 44.6%, p < 0.01), but not in the MLB group (lumen patency: 89.3%). The ET-1 level was reduced in the MLP plus SAH group (34%, p < 0.01) when compared with the SAH groups (SAH only and vehicle). MLB dose-dependently increased the level of eNOS when compared with the vehicle plus SAH group. However, the administration of L-NAME reversed the expression of eNOS and vasoconstriction (lumen patency: 56.2%) in the MLB group. The enhanced expression of eNOS and decreased ET-1 levels in the MLB groups may reflect its anti-spastic effect. In the study of NOS, L-NAME reversed MLB's anti-vasospastic effect. This finding lends credence to the hypothesis that MLB modulates ET-1 levels through a NOS-dependent mechanism in the pathogenesis of cerebral vasospasm following SAH.Acta Neurochirurgica 08/2011; 153(11):2211-7. · 1.55 Impact Factor