Effect of the Histamine Antagonist Cimetidine on Infarct Size in the Rat

We determined whether the histamine H₂ antagonist cimetidine would reduce infarct volume in a model of photochemically-induced thrombotic infarction. Rats were pretreated with either vehicle (n = 6), 5.0 mg/kg cimetidine (n = 6), or 20.0 mg/kg (n = 6) cimetidine 30.0 min prior to infarct formation. Cortical infarction was produced by irradiating the brain with green light (560 nm) through the intact skull for 4 min following the systemic injection of rose bengal. Five days after infarct induction, rats were perfusion-fixed and processed for routine histopathologic analysis. With computer-assisted planimetry, infarct areas and volumes were determined using multiple coronal sections spanning the anterior-posterior extent of the infarct. Morphologic analyses of infarct volume demonstrated no differences between the vehicle (56.0 ± 6 mm³), 5.0 mg/kg cimetidine (50.0 ± 8 mm³), or 20.0 mg/kg cimetidine (53.0 ± 7 mm³) treated groups. In this cortical infarct model, pretreatment with a histamine antagonist fails to reduce infarct size. It is concluded that photochemically-induced microvascular thrombosis results in too severe an insult for cimetidine to chronically protect.