Interplay between adrenaline and interbeat interval on ventricular repolarisation in intact heart in vivo

The aim was to examine the hypothesis that an interaction between adrenaline and change in heart rate may alter the normal time sequence of ventricular repolarisation (and hence refractoriness) in a manner that (1) may favour arrhythmia formation, (2) may partly explain conflicting reports of the effect of adrenaline, ie, there are two opposing effects on action potential duration, and (3) be relevant to T wave abnormalities that sometimes occur in normal people.

As a measure of the time course of repolarisation, monophasic action potentials were recorded simultaneously from three epicardial sites in the porcine heart (left ventricular apex, left ventricular base, and mid right ventricle). During steady state pacing, test pulse intervals were interposed at progressively shorter intervals in order to construct restitution curves.

Adrenaline infusion (0.4-1.5 micrograms.kg-1.min-1) resulted in earlier repolarisation in the beats after shorter interbeat intervals, and delayed repolarisation after longer interbeat intervals, tending to turn the restitution curve anticlockwise (ie, there were two opposing effects on action potential duration). The effects were not homogeneous between regions. To show this inhomogeneity, pairs of monophasic action potentials from different regions were subtracted using a differential input amplifier to produce an ECG like waveform at the amplifier output. The resulting T wave was thereby a measure of the time difference in repolarisation between the monophasic action potentials from which it was derived. The inhomogeneity of repolarisation induced by adrenaline and rate change was reflected in the morphology of this derived T wave, particularly at early (premature) beats. These T wave changes correlated closely with the true T wave changes in bipolar electrograms recorded between the same recording sites (R = 0.89; p less than 0.0001).

These results show that adrenaline altered the normal relationship between interbeat interval and the timing of repolarisation. The effect was not homogeneous and when regional differences were observed they were reflected in changes in T wave morphology. These were marked at short intervals. It is possible that in addition to increased excitability observed with adrenaline, a combination of raised sympathetic activity and early beats predisposes to arrhythmias by exaggerating dispersion of repolarisation.