Antithrombotic therapy in an experimental model of acute ischemic stroke in rabbits

Background

A wide variety of drugs are currently being tested for the management of acute ischemic stroke. Glycoprotein IIb/IIIa inhibitors and low molecular weight heparins show great therapeutic potential in the management of acute ischemic stroke. This trial tested the effects of enoxaparin, tirofiban and the combination of both over infarct volume, short-term clinical outcome, and the risk of intracerebral hemorrhage (ICH) in an animal experimental model.

Methods

An autologous fibrin-rich clot was introduced in the common carotid artery. Two hours after embolization, placebo, enoxaparin, tirofiban, or enoxaparin/tirofiban was infused intravenously over 30 min. The neurologic deficit was evaluated using a neuroscore 24 and 48 hours after the stroke. The incidences of ICH and infarct volume were evaluated through histologic analysis.

Results

The infarct volume was larger in the placebo group than in the enoxaparin, tirofiban and enoxaparin/tirofiban groups. The neuroscore at 24 and 48 hours was higher for the group receiving both drugs simultaneously. No ICH was present in any of the groups (Table 1).

Table 1

Conclusion

It is probable that besides the anticoagulant and antiaggregant effects of enoxaparin and tirofiban, other intrinsic effects of each drug have an impact on the infarct's volume. Combining both drugs resulted in a synergic effect, probably due to prevention of reperfusion damage. A slight improvement of the short-term clinical outcome could be seen with the drugs, meaning that with less tissue damage, better long-term clinical improvement is expected. In this trial, none of the drugs increased the risk of ICH. Further investigation must be done to define the right therapeutic window of opportunity for both of these agents.