Propranolol unmasks class III like electrophysiological properties of norepinephrine.
Isolated perfused spontaneously beating rabbit hearts were treated with increasing concentrations of norepinephrine (0.01, 0.1, 0.5 mumol/l) either alone or in presence of propranolol (0.1 mumol/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 < or = 5 degrees). 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 mumol/l) led to an increase in left ventricular pressure, heart rate and DISP with concomitant 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 mumol/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 diminished. These effects could be prevented by pretreatment with 1 mumol/l prazosin. From these results we conclude, that norepinephrine prolongs the relative action potential duration via stimulation of alpha 1-adrenoceptor and enhances cellular coupling.(ABSTRACT TRUNCATED AT 250 WORDS)
Dhein
S
S
Institut für Pharmakologie, Universität Köln, Germany.
Gerwin
R
R
Ziskoven
U
U
Schott
M
M
Rump
A F
AF
Zhao
Y
Y
Salameh
A
A
Klaus
W
W
D000200:Action Potentials / Q000187:drug effects; D058668:Adrenergic alpha-1 Receptor Antagonists; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004558:Electric Stimulation; D004566:Electrodes; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology*; D011817:Rabbits; D017725:Ventricular Pressure / Q000187:drug effects
D058668:Adrenergic alpha-1 Receptor Antagonists; D000889:Anti-Arrhythmia Agents; D011433:Propranolol; D009638:Norepinephrine; D011224:Prazosin