(±)-sotalol alters neither the shape of the T wave downslope nor the U wave; a magnetocardiographic study

M cells are a mid-myocardial population of cells which play an important role in the genesis of the ventricular repolarization signal. The pharmacologic responsiveness is different from the one of other myocardial cells. M cells are strongly influenced by class-III antiarrhythmic agents [1], and they are suspected both to contribute to the U wave [2] and to determine the shape of the T wave downslope [3]. We measured the effect of (±)-sotalol on the T wave and on the U wave.

We repeatedly administered (±)-sotalol in dosages of 20 mg by i.v. injection to a healthy proband (age 35 years, BSA 1.84 m²), and we measured high resolution direct-coupled 31-lead magnetocardiograms [4] for 10 min at baseline and for 10 min following each injection. Three different doses were administered with an interval of 30 min between them. The heart signals were averaged [5], and the baseline was adjusted. The study was approved by the ethics committee of the Friedrich-Schiller University Jena and written informed consent was obtained from the proband.

The heart rate decreased from 54 (baseline) to 48 beats min⁻¹ (60 mg), and a prominent U wave with a duration of up to 270 ms was seen. The variations in the shape of the T wave are displayed in Figure 1. With increasing doses the U wave was progressively overlapped by the end of the T wave (b), but the U wave shape was completely unaffected by the different dosage levels (c). The QT interval increased from 450 to 530 ms. The shapes of the downslopes of the T waves paralleled at all dosage levels (c), and the decline of a tangent fitted to these slopes was almost identical at all dosage levels (mean decline of −90.7 pT/s at baseline, −93.9, −84.8, and −90.0 pT/s at dosages of 20, 40, and 60 mg, respectively).

Figure 1.

Shapes of the T and U waves at different dosage levels of (±)-sotalol. The signals in the dotted rectangles were magnified in the insets b and c, respectively. (bold to thin: baseline to 60 mg). The number of averaged beats was 546 (baseline), 517 (20 mg), 509 (40 mg), and 483 (60 mg).

(±)-sotalol neither altered the shape of the T wave downslope nor did it affect the U wave. Supposing that the repolarization of the M cells, the last to repolarize, coincides with the end of the T wave and the M cells are the preferential target of the drug, different shapes of the T wave downslope should be expected. We did not observe this effect which has been postulated as a result of tissue experiments. Therefore, a prolongation of the M cell action potential duration can not be simply assessed by quantifying the shape of the T wave downslope. Apparently, the U wave is not connected with M cell activity. More research has to be done to define the origin of this wave.