title: Sympathomimetic modulation of load-dependent changes in the action potential duration in the in situ porcine heart.
abstract: OBJECTIVE
  Increased sympathetic stimulation is known to be arrhythmogenic. Likewise increased loading of the myocardium can directly generate arrhythmias. 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 action potential duration secondary to increased loading. This was investigated during steady-state pacing and during an alteration in beat-to-beat interval in the form of a restitution curve.
  
  
  METHODS
  Pigs were anaesthetised and their hearts exposed. Monophasic action potentials and segment lengths were recorded from the anterior surface of the left ventricle. The loading of the ventricle was increased by transiently occluding the aorta. Steady-state pacing and a restitution curve were performed. 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 potential duration increased with the dose of dobutamine up to 10 micrograms/kg/min after which a plateau was reached. By comparison to control, dobutamine depressed the electrical restitution curve at short test pulse intervals did not significantly alter the plateau. Increased loading elevated the initial section of the electrical restitution curve at short test pulse intervals and depressed the plateau in both the control recordings and those taken during dobutamine infusion. Increased loading increased the amplitude of the supernormal phase of the electrical restitution curve in control recordings and those taken during dobutamine infusion. Sympathetic stimulation by dobutamine during the steady state potentiates the effect of mechanoelectric feedback on the myocardium. The effect on the restitution curve varies with test pulse interval. At short test pulse intervals the effect of sympathetic stimulation dominates with only minor antagonistic modification by increased loading. However, at longer test pulse intervals the effect of mechanoelectric feedback is equal to that of sympathetic stimulation and is synergistic with it.
  
  
  CONCLUSIONS
  The mechanically induced changes we describe in the normal pig heart in situ are relatively small. However, they are in the right direction to possibly contribute to arrhythmia under pathological conditions where mechanical as well as electrophysiological inhomogeneity is prominent.
authors.affiliation: Department of Physiology, Charing Cross and Westminster Medical School, Hammersmith, London, UK.
authors.forename: S M
authors.initials: SM
authors.lastname: Horner
authors.forename: C F
authors.initials: CF
authors.lastname: Murphy
authors.forename: B
authors.initials: B
authors.lastname: Coen
authors.forename: D J
authors.initials: DJ
authors.lastname: Dick
authors.forename: M J
authors.initials: MJ
authors.lastname: Lab
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D002304:Cardiac Pacing, Artificial; D004280:Dobutamine / Q000494:pharmacology*; D005246:Feedback; D005260:Female; D006321:Heart / Q000187:drug effects*; D008297:Male; D015398:Signal Transduction / Q000502:physiology*; D013552:Swine
chemical_list: D004280:Dobutamine