PROPRANOLOL UNMASKS CLASS-III LIKE ELECTROPHYSIOLOGICAL PROPERTIES OFNOREPINEPHRINE

Isolated perfused spontaneously beating rabbit hearts were treated wit h increasing concentrations of norepinephrine (0.01, 0.1, 0.5 mumol/l) either alone or in presence of propranolol (0.1 mumol/1). For analysi s of the epicardial activation and repolarization process and epicardi al 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 determine d. At each electrode an activation vector (VEC) was calculated giving direction and velocity of the local excitation wave. The beat similari ty of various heart beats (under NE) compared to control was evaluated by determination of the percentage of identical BTP and of similar VE C (deviation less-than-or-equal-to 5-degrees). Moreover at each electr ode the local activation recovery interval (ARI) and its standard devi ation (of 256 leads, dispersion, DISP) were determined. Norepinephrine alone (0.01, 0.1, 0.5 mumol/1) led to an increase in left ventricular pressure, heart rate and DISP with concomittant frequency dependent r eduction in ARI, and to changes in the epicardial activation pattern ( reduction in BTP, VEC). We found that in the presence of propranolol ( 0.1 mumol/1) norepinephrine prolonged ARI and reduced ARI-dispersion. This effect was not due to changes in heart rate. The disturbing effec ts on the activation pattern were dimished. These effects could be pre vented by pretreatment with 1 mumol/l prazosine. From these results we conclude, that norepinephrine prolongs the relative action potential duration via stimulation of alpha1-adrenoceptor and enhances cellular coupling. Thus, the antiarrhythmic properties of propranolol may at le ast in part be due to an unmasking of class III like norepinephrine ef fects and additional reduction in dispersion.