Metabolic, electrocardiographic, and hemodynamic responses to increased circulating adrenaline: effects of selective and nonselective beta adrenoceptor blockade.

Twelve healthy male volunteers were given adrenaline infusions, 0.05 microgram/kg body weight/minute over one hundred twenty minutes (min), in order to achieve serum adrenaline concentrations comparable with those seen in acute myocardial infarction. The infusions were given on three occasions, at intervals of at least four weeks. Before the infusions the subjects were given, in random order, two days' pretreatment with placebo, a beta-1-selective adrenoceptor blocker (atenolol), or a nonselective beta blocker (propranolol) with each subject receiving each pretreatment. Six of the volunteers also had a fourth adrenaline infusion, after two days' pretreatment with a beta-2-selective beta blocker, ICI 118551. Adrenaline increased heart rate by 11 beats/min, increased systolic blood pressure by 10 mmHg, and decreased diastolic blood pressure by 15 mmHg. These changes were partly prevented by atenolol. Propranolol and ICI 118551 partly prevented the rise in systolic blood pressure but differed from atenolol in their effects on heart rate and diastolic blood pressure, causing falls in heart rate by 7 beats/min and 12 beats/min respectively, secondary perhaps to increases in diastolic blood pressure by 13 mmHg and 17 mmHg respectively. Adrenaline caused a prolongation of QTc duration by 0.03 second and a flattening of the T-wave amplitude by 1.04 mm. These changes in cardiac repolarization were partly inhibited by atenolol, but the effects of propranolol and ICI 118551 were greater, each causing a reduction of QTc and an increase in T-wave amplitude. During adrenaline infusion S-potassium declined by 0.60 mmol/L, S-magnesium by 0.05, S-calcium by 0.10, and S-phosphate by 0.24, but S-free fatty acids increased nearly threefold. All these changes were statistically significant and were presumably mediated mainly by the beta-2-adrenoceptor, for they were blocked more effectively by the beta-2-adrenoceptor blockers than by the selective beta-1-adrenoceptor blocker. B-glucose increased by 4.1 mmol/L, the increase being practically unaffected by the different pretreatments. These adrenaline-induced hemodynamic, electrocardiographic, and metabolic changes may predispose to arrhythmias and impair cardiac performance after a myocardial infarction. Nonselective beta blockers may be more effective in blocking the electrocardiographic and metabolic effects, but beta-1-selective beta blockers may have hemodynamic advantages.