(S)-EMOPAMIL REDUCES BRAIN EDEMA FROM COLLAGENASE-INDUCED HEMORRHAGE IN RATS

Background and Purpose Calcium channel blockers reduce edema due to cerebral ischemia, but little is known about their usefulness in hemorrhage. Therefore, we studied the effect of the calcium channel blocker (S)-emopamil in collagenase-induced hemorrhage. Methods Adult rats had hemorrhagic necrosis induced by the intracerebral injection of 0.4 U of bacterial collagenase. Six groups of rats were given either 10 or 20 mg/kg (S)-emopamil at different times after induction of the lesion. Brain water and electrolyte levels in these rats were measured 24 hours after collagenase injection. Also, lesion volume in other rats was measured either 4 or 24 hours after formation of the lesion with the drug given at 1 hour or both 1 and 5 hours, respectively. Results Administration of 20 mg/kg (S)-emopamil 1 hour after lesion induction significantly decreased water and electrolyte content in both posterior regions (P<.05). This beneficial effect was lost when a second 20-mg/kg dose was given at 5 hours. A single 20-mg/kg injection at 1 hour had no effect on lesion volume at 4 hours. Two doses significantly increased volume at 24 hours (P<.05). Conclusions Early administration of (S)-emopamil is beneficial in hemorrhagic lesions, but a subsequent delayed injection may be deleterious. Knowledge of the time of hemorrhage will be important in use of these agents in treating hemorrhage.