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Effect of recombinant streptokinase on the development of chronic cerebral vasospasm after subarachnoid hemorrhage in a swine model

  • Experimental research
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Abstract

Background

After subarachnoid hemorrhage (SAH), the formation of subarachnoid clots and their associated resolution may be involved in the development of chronic cerebral vasospasm. To dissolve and wash out the subarachnoid clot is one of the therapeutic strategies for prevention of cerebral vasospasm.

Objective

We investigated the effect of recombinant streptokinase (r-SK), a synthetic plasminogen activator, which is added to degenerate oxyhemoglobin, one of the strongest spasmogenic substances. The efficacy and safety of this therapy concerning the development of chronic cerebral vasospasm were evaluated in a swine model.

Methods

Eighteen healthy porcine subjects were used. Each was randomly assigned to one of three groups: saline control (A), SAH treated with saline (B), and r-SK injection into the cisterna magna (C). SAH was produced by introduction of blood clots into the cisterna magna on each of 2 days in all subjects in groups B and C. At 24-h post-SAH, a one-time dosage of 15 mg of r-SK was administered to those subjects randomized to group C. Continuous drainage was applied in all three groups. Vessel diameter was evaluated by angiography before the induction of SAH and at day 7 following SAH.

Results

The pre- and post-SAH angiographs of subjects in group A determined no significant difference in mean vessel caliber. In group B, pre- and post-SAH angiography indicated significant (p < 0.05) reductions of the mean vessel caliber of the right internal carotid artery (ICA) and basilar artery (BA) compared with the baseline values before SAH. In the r-SK treated group, the mean percent reduction in vessel caliber of the right ICA and BA on day 7 angiograms showed no significant difference compared with the baseline value before SAH.

Conclusions

Chronic cerebral vasospasm was inhibited in the animals to whom r-SK was administered for 1 day after double administration of blood clots to the cisterna magna to induce SAH. The results suggest that the post-SAH presence of subarachnoid clots that contain oxyhemoglobin might be involved in the pathogenesis of vasospasm. Further degeneration of these clots by r-SK may have a promising effect for prevention of vasospasm.

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Authors and Affiliations

  1. Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai Neurosurgical Center, Wulumuqi Zhong Road 12#, Shanghai, 200040, China

    Hongzhi Xu, Xiancheng Chen, Zhiyong Qin, Yuxiang Gu & Ping Zhou

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  1. Hongzhi Xu
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  2. Xiancheng Chen
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  3. Zhiyong Qin
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  4. Yuxiang Gu
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  5. Ping Zhou
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Correspondence to Zhiyong Qin.

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Comment

To date, neurosurgeons have become quite adept at managing the consequences of intracranial bleeds—elevated intracranial pressures and mass effect; however, we remain frustrated by the difficulty intracranial bleeds present when removal is necessary. Large clots may be resected, but diffuse bleeds cannot be reasonably removed and so may remain for a patient's own body to slowly resorb, a process commonly taking weeks. The CLEAR trial recently showed us that intraventricular hemorrhages may be safely removed at an accelerated pace through the injection of thrombolytics (1). This has opened a new avenue for clinicians treating diffuse intracranial bleeds.

The authors have applied the use of thrombolytics in this instance to a porcine model of subarachnoid hemorrhage. Their results are encouraging, demonstrating a reduction of oxyhemaglobin and cerebral vasospasm with cisternal thrombolytic injections. It must be noted that the model used does not simulate aneurysmal rupture itself. Thrombolytics carry the frightening risk of exacerbating intracranial bleeding in actively or recently ruptured aneurysm patients, and this scenario is not addressed in this article's study. Nonetheless, the results are intriguing and will, hopefully, be expanded by future studies.

Markus J. Bookland,

Christopher Loftus

Philadelphia, PA

1. Morgan T, Awad I, Keyl P, et al. (2008) Preliminary report of the clot lysis evaluating accelerated resolution of intraventricular hemorrhage (CLEAR-IVH) clinical trial. Acta Neurochir Suppl 105:21720.

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Xu, H., Chen, X., Qin, Z. et al. Effect of recombinant streptokinase on the development of chronic cerebral vasospasm after subarachnoid hemorrhage in a swine model. Acta Neurochir 153, 1333–1338 (2011). https://doi.org/10.1007/s00701-011-0954-0

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