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Comparative direct electrophysiological effects of propofol on the conduction system and ionic channels of rabbit hearts
Author(s) -
Wu MeiHwan,
Su MingJai,
SiuMun Sun Selma
Publication year - 1997
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701155
Subject(s) - propofol , electrophysiology , refractory period , intracardiac injection , effective refractory period , myocyte , medicine , chemistry , antiarrhythmic agent , anesthesia , biophysics , cardiology , biology , heart disease
Propofol, an intravenous anaesthetic agent, can affect cardiac conduction but the ionic mechanisms have not been well defined. This study measured the direct effects of propofol on the cardiac conduction system by using intracardiac recording/stimulation in Langendorff‐perfused rabbit hearts. The underlying ionic mechanism was elucidated by using the whole‐cell voltage clamp on rabbit isolated atrial and ventricular myocytes. Propofol prolonged significantly the AV conduction (AH) interval at a clinically relevant concentration (3 μ M ). This AH interval prolongation was dose‐dependent (3 to 100 μ M ). At higher concentrations, the AV nodal Wenckebach cycle length and its refractory period were also prolonged (10 to 100 μ M ). In addition, the conduction through the His‐Purkinje system (HV interval) and the atrial tissue (SA interval), as well as the spontaneous cycle length, were lengthened dose‐dependently (30 to 100 μ M ). In isolated ventricular myocytes, Na current was decreased dose‐dependently by propofol. In part this was due to a negative‐shift of the steady‐state voltage‐dependent inactivation and a slowed rate of recovery from inactivation. The I Na suppression by propofol was frequency‐dependent. Propofol also blocked the I Ca . The ED 50 for peak current inhibition was 6.9±0.9 ( n =6) and 8.3±1.5 μ M ( n =7) for I Na and I Ca , respectively. The transient outward potassium current ( I to ) of atrial myocytes was suppressed with an ED 50 of 5.7±0.8 μ M ( n =11), which was only partly caused by a left‐shift of the steady‐state inactivation. The inward rectifier K current ( I K1 ) of the ventricular cells was reduced somewhat by propofol. In summary, propofol can cause direct dromotropic and chronotropic effects on the cardiac conduction system, especially the atrioventricular node. These changes can be attributed, at least in part, to its direct dose‐dependent suppression of the cardiac I Ca , I Na and I to . Special concerns in the use of propofol anaesthesia for cardiac patients and the therapeutic antiarrythmic potential of propofol‐like compounds are addressed.British Journal of Pharmacology (1997) 121 , 617–624; doi: 10.1038/sj.bjp.0701155