The relationship between heart rate and QT interval was investigated during atrial stimulation (intrinsic effect of heart rate) in ten healthy male volunteers prior to and after administration of sotalol. The QT interval in the ECG (paper speed 200 mm/s) was determined at rates of 70, 85, 100, 115, 130, 145, and 160 beats/min and at pacing periods of 180 s each at 30, 60, 120, and 180 s. After a 15-minute period, 2.0 mg sotalol/kg body weight were administered iv and the stimulation protocol was repeated. The analysis of QT interval behavior reveals contradictions to the mathematical implications of Bazett's equation QT = QTc square root of 60/HR, so that the relationship between heart rate and QT interval is not adequately described under the given conditions. After examination of approaches reported in the literature and our own approaches, the expression QT = a e-b (HR-60) is used as a possibility differentially to describe the data by nonlinear regression. The parameters a and b may be interpreted as QT reference value and shortening parameter. The QT reference value a, a parameter in reference to heart rate of 60 beats/min, has a comparable significance to the expression QTc in the Bazett equation. A reduction in the shortening parameter b indicates whether substances influencing the QT interval additionally produce overproportional shortening of the QT interval with increasing heart rate. After administration of sotalol, an increase can be observed in both the QT reference value and also in the shortening parameter. The suggested approach is an attempt to provide a more precise assessment of the QT interval under different conditions.

Beta-adrenoceptor stimulation in vivo shifts potassium into the cells. To examine whether human erythrocytes participate in this process, we measured, along with serum or plasma potassium, the concentrations of potassium and sodium in erythrocytes. Beta-adrenoceptor stimulation was obtained by infusion of either fenoterol or hexoprenaline into 6 volunteers at rest or by endogenous amines provoked in 14 volunteers during ergometric exercise. Metabolic effects were followed at rest on serum insulin, C-peptide, and growth hormone levels, and during exercise on pH on lactate concentration in blood. The potassium concentration (mean +/- S.E.M.) dropped (p less than 0.01) in serum from 4.64 +/- 0.37 to 3.19 +/- 0.43 mmol x l-1 in the first hour at rest and in plasma from 5.70 +/- 0.93 to 4.63 +/- 0.45 in 90 sec directly after exercise. The concentration of erythrocyte sodium dropped (p less than 0.001) from 9.68 +/- 0.73 to 8.81 +/- 0.62 mmol x l-1 in cells and from 9.62 +/- 1.16 to 8.55 +/- 1.24 during exercise for 90 s, respectively. Changes in the concentration ratio of cellular sodium to potassium confirmed this sodium shift. An increased sodium transport in erythrocytes due to beta-adrenoceptor stimulation in vivo appears to complement a shift of serum potassium into the cells and may be mediated by the membrane-bound sodium, potassium ATPase.

In 35 pregnant women threatening premature labour and cervic dilatation indicated therapy by a beta-mimetic compound (fenoterol) for tocolysis. 17 patients (group I) got fenoterol-monotherapy; in 18 patients (group II) fenoterol was combined with the cardioselective beta-1-blocking agent metoprolol. There were no differences in age, bodyweight and time of gestation in both groups before therapy; also the obstetric states--as compared by pelvic score (Bishop) and tocolysis index (Baumgarten)--were nearly identical. Efficiency of tocolytic therapy was evaluated by prolongation index (Richter) and tocolysis-success-score (Weidinger). Statistical analysis comparing these parameters in both groups showed no significant differences. Heartrate, however, was significantly (p > 0,005) lower in patients treated by fenoterol and metoprolol, thus indicating less cardial stress induced by fenoterol. In conclusion the combination of the semiselective beta-2-stimulating compound fenoterol with the beta-1-blocking agent metoprolol is proposed for tocolytic therapy because of less cardial stress but identical tocolytic efficiency as compared with fenoterol-monotherapy.