Intracerebral Hemorrhage in Rats

Background and Purpose Beneficial effects of calcium antagonists in cerebral ischemia and trauma have been attributed in part to improved cerebral blood flow. Enhancement of cerebral blood flow, however, could aggravate the pathological situation if brain injury is associated with intracerebral hemorrhage. In this study we used high-field magnetic resonance imaging in an animal model of intracerebral hemorrhage to determine noninvasively the effect of the calcium and serotonin antagonist levemopamil [international nonproprietary name for (S)-emopamil] when infused in a dose (6 mg/kg) that is known to increase cerebral blood flow. Methods Intracerebral hemorrhage was induced in rats by stereotaxic microinfusion of collagenase into the caudate putamen. Two series of experiments were performed. (1) Levemopamil was intravenously infused 30 minutes after intracerebral infusion of collagenase (0.05 U), which represents the time of intracranial bleeding. Another group of animals was given heparin (55 IU • kg" • min") to evaluate the capability of this animal model to demonstrate drug-induced worsening of intracerebral hemorrhage. (2) The effects of hyperacute infusion of levemopamil (30 minutes after infusion of 0.5 U of collagenase) were compared with those of a 2-hour delayed administration. In both experimental settings, the extent of intracerebral hemorrhage was determined by T,weighted magnetic resonance images (spin-echo; repetition time, 400 milliseconds; echo time, 23 milliseconds) taken in