κ－阿片激动剂增高心室易颤性及其机制

研究结果表明，在离体心脏Ｌａｎｇｅｎｄｏｒｆｆ模型，κ－阿片激动剂Ｕ５０４８８Ｈ可降低心室颤动阈（ＶＦＴ）、有效不应期（ＥＲＰ）和舒张期兴奋阈（ＤＥＴ）；且可被特异。桔抗剂ＭＲ２２６６所阻断。硝苯吡啶和细胞外低钙预处理可取消Ｕ５０４８８Ｈ的心脏作用。Ｒｙａｎｏｄｉｎｅ预处理可取消Ｕ５０４８８Ｈ对ＥＰＰ和ＤＥＴ的作用，但不能取消其降低ＶＦＴ的作用、结果提示，Ｕ５０４８８Ｈ激活κ－受体具致心律失常作用，这一作用主要依赖于跨膜钙内流。

Increase of ventricular vulnerability by k-opioid agonist and its mechanism

Langendorff model of the isolated perfused rat heart was used.It was found that U50 488H,a specific k-opioid agonist,decreased ventricular fibrillation threshold(VFT),effective refractory period(ERP)and diastolic excitatory threshold(DET),and the cardiac effects of U50 488H were abolished by MR2266,a specific k-antagonist.The enhanced vulnerability to ventricluar fibrillation induced by U50 488H could be prevented by inhibition of transsarcolemmal Ca2+ ion influx by nifedipine and by subphysiological extracellular calcium concentration(0.75 mmol·L-1).Pretreatment With rysnodine canceled the effect of U50 488H on ERP and DET,but did not altered the effectof U50 488H on VFT.The results suggest that the arrhythmogenic effect of cardiac k-receptors activated by U50 488H mainly depends upon transsarcolemmal Ca2+ influx.