抄録
We had previously reported that activation of histamine H3-receptors (H 3R) on cardiac adrenergic nerve terminals decreases norepinephrine (NE) overfow from ischemic hearts and alleviates reperfusion arrhythmias. Thus, we used transgenic mice lacking H 3R (H3R−/-) to investigate whether ischemic arrhythmias might be more severe in H3R−/- hearts than in hearts with intact H 3R (H3R+/+). We report a greater incidence and longer duration of ventricular fibrillation (VF) in H3R−/- hearts subjected to ischemia.VF duration was linearly correlated with NE overfow, 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 H3R in myocardialischemia. Since malignant tachyarrhythmias cause sudden death in ischemic heart disease, attenuation of NE release by selectiveH3R agonists may represent a new approach in the prevention and treatment of ischemic arrhythmias. [Jpn J Physiol 54 Suppl:S60 (2004)]
