Direct effect of dobutamine on action potential duration in ischemic compared with normal areas in the human ventricle.
OBJECTIVE
The arrhythmogenic effect of beta-adrenoceptor stimulation is complex and may differ in ischemic and normal myocardium. In this study we examined the differential effect of beta-adrenergic stimulation on ventricular action potential duration and, hence, dispersion of repolarization in potentially ischemic versus nonischemic human ventricular myocardium.


METHODS
Simultaneous biventricular monophasic action potentials were recorded in 14 patients (28 recording sites) during infusion of dobutamine in incremental doses (low dose 5 micrograms/kg per min, high dose 10 to 15 micrograms/kg per min) during atrial pacing. Perfusion at the action potential recording site was assessed by incorporating myocardial perfusion scintigraphy with injection of technetium-99m hexakis-2-methoxy-2-methylpropyl-isonitrile during the recording at peak doses of dobutamine. Action potential duration during dobutamine infusion was compared with that during atrial pacing to identical rates in the absence of dobutamine.


RESULTS
In 21 normal zone recordings, dobutamine produced a variable effect over that produced by atrial pacing to identical heart rates, either lengthening or shortening the action potential duration. The mean (+/- SEM) value for the additional effect of dobutamine was 0.9 +/- 2.5 ms with low doses and -4 +/- 2.6 ms with high doses (p = NS). In seven recordings from potentially ischemic zones, low dose dobutamine had a similar effect (mean change -3.4 +/- 6.5 ms; p = NS vs. normal zone values). However, the high dose dobutamine invariably shortened the action potential duration by a mean of -22.9 +/- 2.9 ms. (p less than 0.05 vs. low dose in ischemic areas, p less than 0.01 vs. normal zone recordings). Pacing alone or the addition of dobutamine had no significant effect on the normal dispersion of action potential duration between two nonischemic recording sites. In recordings in a normal and an abnormally perfused site, high dose dobutamine significantly altered the dispersion of action potential duration.


CONCLUSIONS
These results suggest a different effect of beta adrenergic stimulation in potentially ischemic compared with nonischemic human ventricular myocardium. The abnormal dispersion of repolarization thus created may well be important in beta-receptor-mediated arrhythmogenesis during myocardial ischemia.
John
R M
RM
Department of Cardiology, Middlesex Hospital, London, England.
Taggart
P I
PI
Sutton
P M
PM
Ell
P J
PJ
Swanton
H
H
D000200:Action Potentials / Q000187:drug effects; D002304:Cardiac Pacing, Artificial; D003287:Contrast Media; D003327:Coronary Disease / Q000000981:diagnostic imaging / Q000503:physiopathology*; D004280:Dobutamine / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging; D006329:Heart Conduction System / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D015609:Organotechnetium Compounds; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D017256:Technetium Tc 99m Sestamibi; D015899:Tomography, Emission-Computed, Single-Photon; D016276:Ventricular Function / Q000187:drug effects*
D003287:Contrast Media; D009570:Nitriles; D015609:Organotechnetium Compounds; D011943:Receptors, Adrenergic, beta; D004280:Dobutamine; D017256:Technetium Tc 99m Sestamibi