ヒスタミンH3レセプターノックアウトマウスにおける虚血時ノルエピネフリン放出と再灌流時不整脈

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)]