Kaumann A J, Sanders L
Clinical Pharmacology Unit, University of Cambridge, Addenbrooke's Hospital, UK.
Naunyn Schmiedebergs Arch Pharmacol. 1993 Nov;348(5):536-40. doi: 10.1007/BF00173215.
The involvement of beta 1- and beta 2-adrenoceptors in catecholamine-evoked arrhythmias was investigated in isolated human right atrial appendages obtained from 22 patients chronically treated with beta blockers (usually beta 1-selective) and 9 patients not treated with beta blockers. A simple experimental model that assesses the incidence of arrhythmic contractions as a function of heart rate (pacing) is introduced. beta 1-adrenoceptors were activated by (-)-noradrenaline during beta 2-adrenoceptor blockade with 50 nmol/l ICI 118551. beta 2-adrenoceptors were activated by (-)-adrenaline during beta 1-adrenoceptor blockade with 300 nmol/l CGP 20712A. Both (-)-noradrenaline and (-)-adrenaline caused arrhythmic contractions whose incidence was greater at low than at high pacing rates. CGP 20712A (300 nmol/l) blocked the (-)-noradrenaline-evoked contractions in 1/1 atrial strip from 1/1 patient not treated with a beta blocker and 17/17 atrial strips from 15/15 patients chronically treated with beta blockers. ICI 118551 (50 nmol/l) blocked the (-)-adrenaline-evoked contractions in 3/4 atrial strips from 3/4 patients not treated with beta blockers and 17/20 atrial strips from 15/18 patients chronically treated with beta blockers. The incidence of arrhythmic contractions evoked by both (-)-noradrenaline and (-)-adrenaline was higher in chronically beta blocked patients than in non beta blocked patients. We conclude that both beta 1- and beta 2-adrenoceptors mediate atrial arrhythmias and that the generation of these arrhythmias is facilitated by chronic beta 1-adrenoceptor blockade.
在取自22例长期接受β受体阻滞剂（通常为β1选择性）治疗的患者以及9例未接受β受体阻滞剂治疗的患者的离体人右心耳中，研究了β1和β2肾上腺素能受体在儿茶酚胺诱发心律失常中的作用。引入了一个简单的实验模型，该模型可评估心律失常性收缩的发生率与心率（起搏）的关系。在用50 nmol/l ICI 118551阻断β2肾上腺素能受体期间，通过（-）-去甲肾上腺素激活β1肾上腺素能受体。在用300 nmol/l CGP 20712A阻断β1肾上腺素能受体期间，通过（-）-肾上腺素激活β2肾上腺素能受体。（-）-去甲肾上腺素和（-）-肾上腺素均引起心律失常性收缩，其发生率在低起搏频率时高于高起搏频率。300 nmol/l的CGP 20712A阻断了1例未接受β受体阻滞剂治疗患者的1条心房肌条以及15例长期接受β受体阻滞剂治疗患者的17条心房肌条中（-）-去甲肾上腺素诱发的收缩。50 nmol/l的ICI 118551阻断了4例未接受β受体阻滞剂治疗患者的3条心房肌条以及18例长期接受β受体阻滞剂治疗患者的20条心房肌条中15例患者的（-）-肾上腺素诱发的收缩。长期接受β受体阻滞剂治疗的患者中，（-）-去甲肾上腺素和（-）-肾上腺素诱发的心律失常性收缩的发生率高于未接受β受体阻滞剂治疗的患者。我们得出结论，β1和β2肾上腺素能受体均介导心房心律失常，并且慢性β1肾上腺素能受体阻断促进了这些心律失常的发生。
