Summary
Isolated perfused spontaneously beating rabbit hearts were treated with increasing concentrations of norepinephrine (0.01, 0.1, 0.5 μmol/l) either alone or in presence of propranolol (0.1 μmol/l). For analysis of the epicardial activation and repolarization process and epicardial mapping (256 unipolar leads) was performed. For each electrode the activation and repolarization time was determined. From these data the “breakthrough-points” (BTP) of epicardial activation were determined. At each electrode an activation vector (VEC) was calculated giving direction and velocity of the local excitation wave. The beat similarity of various heart beats (under NE) compared to control was evaluated by determination of the percentage of identical BTP and of similar VEC (deviation ≤5°). Moreover at each electrode the local activation recovery interval (ARI) and its standard deviation (of 256 leads, dispersion, DISP) were determined. Norepinephrine alone (0.01, 0.1, 0.5 μmol/l) led to an increase in left ventricular pressure, heart rate and DISP with concomittant frequency dependent reduction in ARI, and to changes in the epicardial activation pattern (reduction in BTP, VEC). We found that in the presence of propranolol (0.1 μmol/l) norepinephrine prolonged ARI and reduced ARI-dispersion. This effect was not due to changes in heart rate. The disturbing effects on the activation pattern were dimished. These effects could be prevented by pretreatment with 1 μmol/l prazosine. From these results we conclude, that norepinephrine prolongs the relative action potential duration via stimulation of α1-adrenoceptor and enhances cellular coupling. Thus, the antiarrhythmic properties of propranolol may at least in part be due to an unmasking of class III like norepinephrine effects and additional reduction in dispersion.
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Supported by the DFG, grant No. Dh 3/1-3
Correspondence to: S. Dhein at the above address
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Dhein, S., Gerwin, R., Ziskoven, U. et al. Propranolol unmasks class III like electrophysiological properties of norepinephrine. Naunyn-Schmiedeberg's Arch Pharmacol 348, 643–649 (1993). https://doi.org/10.1007/BF00167242
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DOI: https://doi.org/10.1007/BF00167242