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.
Leistra
H P
HP
Department of Neurology, University of Miami School of Medicine, FL.
Dietrich
W D
WD
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D002544:Cerebral Infarction / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D002908:Chronic Disease; D002927:Cimetidine / Q000627:therapeutic use*; D006635:Histamine H2 Antagonists / Q000627:therapeutic use*; D006863:Hydrogen-Ion Concentration; D008027:Light; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012395:Rose Bengal; D013238:Stereotaxic Techniques
D006635:Histamine H2 Antagonists; D002245:Carbon Dioxide; D012395:Rose Bengal; D002927:Cimetidine