Increased severity of reperfusion arrhythmias in mouse hearts lacking histamine H3-receptors.

TitleIncreased severity of reperfusion arrhythmias in mouse hearts lacking histamine H3-receptors.
Publication TypeJournal Article
Year of Publication2003
AuthorsKoyama M, Heerdt PM, Levi R
JournalBiochem Biophys Res Commun
Date Published2003 Jul 4
KeywordsAdrenergic alpha-Agonists, Animals, Arrhythmias, Cardiac, Electrocardiography, Female, Humans, Mice, Mice, Transgenic, Myocardial Ischemia, Myocardial Reperfusion Injury, Norepinephrine, Receptors, Histamine H3

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.

Alternate JournalBiochem. Biophys. Res. Commun.
PubMed ID12810089
Grant ListHL34215 / HL / NHLBI NIH HHS / United States
HL46403 / HL / NHLBI NIH HHS / United States