Search

In a prospective study, 20 patients with a first acute myocardial infarction and no current treatment with diuretics or cardioactive drugs were randomized to treatment with intravenous timolol (10 patients) or placebo (10 patients). Plasma adrenaline, noradrenaline, and serum potassium were estimated at baseline (mean +/- SD 3.6 +/- 0.8 hours after the onset of the infarction) and 4 hours after the start of treatment. The patient selection criteria embraced a low-risk study population. Before treatment, the serum potassium concentrations correlated inversely with plasma adrenaline but not with plasma noradrenaline concentrations. A rise of serum potassium (mean +/- SD mmol/L) from 4.1 +/- 0.3 to 4.4 +/- 0.4 (p less than 0.05) in the placebo group and from 4.0 +/- 0.4 to 4.5 +/- 0.5 (p less than 0.05) in the timolol group was in multivariate analysis associated with infarct size, estimated as cumulative creatine kinase release, in the placebo group, and with the mean individual plasma adrenaline concentrations in the timolol group. By reversing the effect of adrenaline from a decrease to an increase in the serum potassium concentrations, timolol changes the relationships between circulating adrenaline, potassium, and infarct size.

In a study of 1033 consecutive patients with acute myocardial infarction, serum potassium concentrations were determined on admission to hospital and studied with respect to the subsequent occurrence of atrial fibrillation and flutter and of ventricular tachycardia and fibrillation. The study cohort fulfilled the inclusion criteria for the Norwegian timolol trial in which they later took part. In multivariate analysis, with serum potassium concentrations as a continuous variable, age, the presence of ventricular tachycardia and fibrillation, and maximum level of aspartate aminotransferase greater than four times the upper limit of normal were significantly associated with the occurrence of atrial fibrillation and flutter, while serum potassium concentration was not. Serum potassium concentrations and time from onset of the infarction to hospital admission were significantly negatively associated with the occurrence of ventricular tachycardia and fibrillation; while age, cardiomegaly, transient hypotension, pathological Q-waves in the electrocardiogram, atrial fibrillation and flutter, and ventricular premature beats were positively related to these arrhythmias. Thus, there is an independent inverse relationship between serum potassium concentrations and ventricular arrhythmias in acute myocardial infarction.

Sixty patients with a first acute myocardial infarction and no current treatment with cardioactive drugs were included in a prospective study of the relationship between serum potassium concentration and the early occurrence of ventricular tachycardia and premature ventricular contractions (PVCs). Serum potassium level (range 2.5 to 5 mmol/liter) was estimated 3.8 +/- 2.5 hr (mean +/- SD) after the onset of the infarction, and Holter monitoring was performed during the subsequent 12 hr. In multivariate analysis, serum potassium level was negatively and age positively related to ventricular tachycardia. Among the subclasses of PVCs (frequent unifocal, multifocal, couplets, bigeminy), serum potassium concentration was negatively related to the frequent unifocal subclass; hypertension was related to couplets and to the presence of any of the subclasses, and serum aspartate aminotransferase concentration was related to multifocal PVCs. Heart failure leading to death was related to all subclasses of PVC. Serum potassium concentration is an independent inverse predictor of the occurrence of ventricular tachycardia and frequent unifocal PVCs early in acute myocardial infarction.

One hundred and six patients with acute myocardial infarction admitted to hospital within four hours after the onset of symptoms were randomised to treatment with intravenous timolol (54 patients) or placebo (52 patients). Serum potassium concentrations were estimated at frequent intervals during the first 24 hours of admission. Patients in both treatment groups, who did not receive subsequent diuretic treatment, had a transient rise in serum potassium concentration, which was maximal after four hours. This rise was abolished by diuretic treatment in the placebo group but not in the timolol group, in which there was a pronounced and prolonged rise in serum potassium concentration. The change in serum potassium concentration in the first four hours after admission correlated with cumulative creatine kinase release in the placebo group, but not in the timolol group. Hypokalaemia (serum potassium concentration less than or equal to 3.5 mmol/l) occurred in 15 (28.8%) patients in the placebo group and in seven (13%) in the timolol group and was independent of infarct size. The frequency of hyperkalaemia was not increased in the timolol group. By increasing the serum potassium concentration and preventing hypokalaemia, the use of intravenous timolol early in acute myocardial infarction may have important clinical effects in addition to reducing infarct size.