title: Increased severity of reperfusion arrhythmias in mouse hearts lacking histamine H3-receptors.
abstract: We had previously reported that activation of histamine H(3)-receptors (H(3)R) on cardiac adrenergic nerve terminals decreases norepinephrine (NE) overflow from ischemic hearts and alleviates reperfusion arrhythmias. Thus, we used transgenic mice lacking H(3)R (H(3)R(-/-)) to investigate whether ischemic arrhythmias might be more severe in H(3)R(-/-) hearts than in hearts with intact H(3)R (H(3)R(+/+)). We report a greater incidence and longer duration of ventricular fibrillation (VF) in H(3)R(-/-) hearts subjected to ischemia. VF duration was linearly correlated with NE overflow, suggesting a possible cause-effect relationship between magnitude of NE release and severity of reperfusion arrhythmias. Thus, our findings strengthen a protective antiarrhythmic role of H(3)R in myocardial ischemia. Since malignant tachyarrhythmias cause sudden death in ischemic heart disease, attenuation of NE release by selective H(3)R agonists may represent a new approach in the prevention and treatment of ischemic arrhythmias.
authors.affiliation: Department of Pharmacology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Koyama
authors.forename: Paul M
authors.initials: PM
authors.lastname: Heerdt
authors.forename: Roberto
authors.initials: R
authors.lastname: Levi
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000378:metabolism; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism* / Q000473:pathology; D004562:Electrocardiography; D005260:Female; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D017202:Myocardial Ischemia; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D009638:Norepinephrine / Q000378:metabolism; D018100:Receptors, Histamine H3 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000316:Adrenergic alpha-Agonists; D018100:Receptors, Histamine H3; D009638:Norepinephrine