Hansen O, Johansson B W, Gullberg B
Section of Cardiology, Malmö General Hospital, Sweden.
Angiology. 1991 Dec;42(12):990-1001. doi: 10.1177/000331979104201209.
In order to study the effects of treatment with class 1 antiarrhythmics on the metabolic, hemodynamic, and electrocardiographic responses to adrenaline, 12 healthy volunteers were infused on four occasions, after pretreatment with placebo, disopyramide, mexiletine, and flecainide, respectively, with adrenaline at a rate producing serum adrenaline concentrations comparable with those seen in acute myocardial infarction. After pretreatment with placebo adrenaline caused significant falls in serum potassium, serum magnesium, serum calcium, and serum phosphate and a significant increase in blood glucose. Adrenaline also caused a significant increase in heart rate and systolic blood pressure and a significant fall in diastolic blood pressure. On the electrocardiogram a significant prolongation of QTc duration and a flattening of the T-wave amplitude were seen. Pretreatment with disopyramide had no effect on the hemodynamic response to adrenaline but caused a significant prolongation of Qtc duration before the adrenaline infusion. Pretreatment with mexiletine was associated with a significantly greater fall in serum potassium during adrenaline infusion, and pretreatment with flecainide with a greater fall in serum magnesium, as compared with placebo pretreatment Flecainide also caused a significant prolongation of the QRS duration before adrenalin infusion, and after all the active pretreatments a prolongation of QRS duration was seen during adrenaline infusion. The metabolic and hemodynamic changes during adrenaline infusion may not only reduce the antiarrhythmic efficacy of antiarrhythmics but may also increase the risk of proarrhythmic effects in a clinical setting. These results may help to explain why treatment with antiarrhythmics seems to be without beneficial effect on mortality in post-myocardial infarction patients.
为了研究Ⅰ类抗心律失常药物治疗对肾上腺素引起的代谢、血流动力学及心电图反应的影响，12名健康志愿者在分别接受安慰剂、丙吡胺、美西律和氟卡尼预处理后，四次输注肾上腺素，输注速率使血清肾上腺素浓度与急性心肌梗死时所见浓度相当。安慰剂预处理后，肾上腺素导致血清钾、血清镁、血清钙和血清磷酸盐显著下降，血糖显著升高。肾上腺素还导致心率和收缩压显著升高，舒张压显著下降。心电图显示QTc间期显著延长，T波振幅降低。丙吡胺预处理对肾上腺素的血流动力学反应无影响，但在输注肾上腺素前导致Qtc间期显著延长。与安慰剂预处理相比，美西律预处理使肾上腺素输注期间血清钾显著下降，氟卡尼预处理使血清镁显著下降。氟卡尼在输注肾上腺素前还导致QRS间期显著延长，所有活性药物预处理后，输注肾上腺素期间QRS间期均延长。肾上腺素输注期间的代谢和血流动力学变化不仅可能降低抗心律失常药物的抗心律失常疗效，还可能增加临床环境中致心律失常作用的风险。这些结果可能有助于解释为什么抗心律失常药物治疗对心肌梗死后患者的死亡率似乎没有有益影响。
