Metabolic,Hemodynamic,and Electrocardiographic Responses to Increased Circulating Adrenaline: Effects of Pretreatment with Class 1 Antiarrhythmics

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 se rum 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 prolon gation of QT_c 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 Qt_c duration before the adrenaline infusion. Pretreatment with mexiletine was associated with a signifi cantly greater fall in serum potassium during adrenaline infusion, and pretreat ment 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 meta bolic 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 mor tality in post-myocardial infarction patients.