SYMPATHOMIMETIC MODULATION OF LOAD-DEPENDENT CHANGES IN THE ACTION-POTENTIAL DURATION IN THE IN-SITU PORCINE HEART

Aims: Increased sympathetic stimulation is known to be arrhythmogenic. Likewise increased loading of the myocardium can directly generate ar rhythmias. The interaction between the two on the electrophysiology of the myocardium has not been investigated before. We investigated the effect of dobutamine infusion on the shortening of the monophasic acti on potential duration secondary to increased loading. This was investi gated during steady-state pacing and during an alteration in beat-to-b eat interval in the form of a restitution curve. Methods: Pigs were an aesthetised and their hearts exposed. Monophasic action potentials and segment lengths were recorded from the anterior surface of the left v entricle. The loading of the ventricle was increased by transiently oc cluding the aorta. Steady-state pacing and a restitution curve were pe rformed. Recordings were taken before and during dobutamine infusion. Results: At steady state, increased loading of the heart shortened the monophasic action potential duration by a mean (+/- s.e.m.) of 4.0 (/- 0.5) ms (P < 0.001), During dobutamine infusion this shortening of the monophasic action potential increased. Shortening of the action po tential duration increased with the dose of dobutamine up to 10 mu g/k g/min after which a plateau was reached. By comparison to control, dob utamine depressed the electrical restitution curve at short test pulse intervals but did not significantly alter the plateau. Increased load ing elevated the initial section of the electrical restitution curve a t short test pulse intervals and depressed the plateau in both the con trol recordings and those taken during dobutamine infusion. Increased loading increased the amplitude of the supernormal phase of the electr ical restitution curve in control recordings and those taken during do butamine infusion. Sympathetic stimulation by dobutamine during the st eady state potentiates the effect of mechanoelectric feedback on the m yocardium. The effect on the restitution curve varies with test pulse interval, At short test pulse intervals the effect of sympathetic stim ulation dominates with only minor antagonistic modification by increas ed loading. However, at longer test pulse intervals the effect of mech anoelectric feedback is equal to that of sympathetic stimulation and i s synergistic with it. Conclusions: The mechanically induced changes w e describe in the normal pig heart in situ are relatively small, Howev er, they are in the right direction to possibly contribute to arrhythm ia under pathological conditions where mechanical as well as electroph ysiological inhomogeneity is prominent.