Intra-arterial administration of recombinant tissue-type plasminogen activator (rt-PA) causes more intracranial bleeding than does intravenous rt-PA in a transient rat middle cerebral artery occlusion model
2011

Comparing Intra-arterial and Intravenous rt-PA for Stroke Treatment in Rats

Sample size: 42 publication Evidence: moderate

Author Information

Author(s): Crumrine R. Christian, Marder Victor J., Taylor G. McLeod, LaManna Joseph C., Tsipis Constantinos P., Scuderi Philip, Petteway Stephen R Jr, Arora Vikram

Primary Institution: Grifols Therapeutics, Inc.

Hypothesis

Intra-arterial administration of rt-PA causes more intracranial bleeding than intravenous rt-PA in a transient rat middle cerebral artery occlusion model.

Conclusion

Intra-arterial administration of rt-PA results in greater intracranial bleeding and worse functional recovery compared to intravenous administration.

Supporting Evidence

  • Greater hemorrhagic transformation occurred with 10 and 30 mg/kg rt-PA administered intra-arterially compared to intravenously.
  • The intravenous 10 mg/kg rt-PA dosage induced significantly less bleeding than the 1 or 5 mg/kg intra-arterial groups.
  • No significant increase in infarct volume was observed after either treatment.
  • Rats treated with 30 mg/kg rt-PA by either route had greater neurological dysfunction compared to all other groups.

Takeaway

Giving a medicine called rt-PA directly into the artery in the brain can cause more bleeding than giving it through a vein, even if the dose is much smaller.

Methodology

Male spontaneously hypertensive rats were treated with either intra-arterial or intravenous rt-PA after 6 hours of middle cerebral artery occlusion, and outcomes were measured 24 hours later.

Potential Biases

Potential bias due to the authors' affiliations with Grifols Therapeutics, Inc.

Limitations

The study had a limited number of rats in some treatment groups, which may affect the generalizability of the results.

Participant Demographics

Adult male spontaneously hypertensive rats weighing 330 - 380 g.

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1186/2040-7378-3-10

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