Ancrod reduces intracerebral hemorrhage quantified in vivo by magnetic resonance imaging in rats

Abstract

Promising results of experimental and clinical stroke studies suggest that ancrod may provide an efficient therapy of brain ischemia. Because ancrod has been shown to produce rapid defibrinogenation, we investigated the effects of this agent in a rat model of intracranial bleeding using noninvasive magnetic resonance imaging (MRI). Intracranial bleeding was induced in anesthetised rats by microinfusion of collagenase into the right striatum. Ancrod was intravenously infused for a period of 30 minutes starting 30 minutes after intrastriatal collagenase infusion. The dosages of ancrod were 0.33 IU . kg(-1) . min(-1) in one group and 1 IU . kg(-1) . min(-1) in another (total dosages were 10 and 30 IU . kg(-1), respectively). Control animals received equal amounts of vehicle solution (0.9% NaCl) only. The volume of intracerebral hemorrhage (ICH) was quantified in vivo by T1-weighted spin-echo MRI in eight consecutive coronal brain planes 24 hours after collagenase infusion. Plasma fibrinogen was dose-dependently diminished immediately after infusion of ancrod at dosages of 0.33 or 1 IU . kg(-1) . min(-1). Total volume of ICH was significantly (P<.05) reduced by 50% from 48 (35/57) mm(3) in vehicle-treated controls (n=17) to 24 (20/37) mm(3) in rats (n=15) infused with the lower ancrod dosage (median, 25th/75th centiles). Rats (n=15) treated with the higher dosage of ancrod had 34 (27/39) mm(3) volume of ICH, which is 29% lower compared with vehicle-treated controls (P=.05). Adverse side effects such as aggravation of intracerebral bleeding did not occur in ancrod-infused rats despite pronounced lowering of the plasma fibrinogen level during ongoing bleeding. In contrast, significant reductions in the volumes of ICH were observed suggesting favorable influence of ancrod in the event of intracranial bleeding in rats.