Effects of intravenous anesthetics on atrial wavelength and atrioventricular nodal conduction in guinea pig heart. Potential antidysrhythmic properties and clinical implications.
BACKGROUND
Supraventricular tachydysrhythmias such as atrial fibrillation frequently complicate the perioperative period. Two electrophysiologic factors critical to the pathogenesis of supraventricular tachydysrhythmias are: 1) atrial wavelength, the product of atrial conduction velocity (CV) and effective refractory period (ERP), and 2) atrioventricular nodal conduction. Modulation of these factors by drugs has important clinical ramifications. The authors studied the effects of propofol, thiopental, and ketamine on atrial wavelength and atrioventricular nodal function in guinea pig isolated atrial trabeculae and hearts, respectively.


METHODS
Electrocardiogram recordings in superfused atrial tissue were obtained using hanging microelectrodes. A stimulating and two recording electrodes were placed on a single atrial trabecula, and the interelectrode distance was measured. Atrial ERP determinations were made using a premature stimulus protocol. The time (t) required for a propagated impulse to traverse the interelectrode distance (d) was measured. Conduction velocity was calculated as d/t. Langendorff-perfused guinea pig hearts were instrumented for low atrial pacing (cycle length = 300 ms) and for measurements of stimulusto-His bundle interval, an index of atrioventricular nodal conduction. To investigate the frequency-dependent behavior of the atrioventricular node, computer-based measurements were made of Wenckebach cycle length (WCL) and atrioventricular nodal ERP.


RESULTS
Thiopental significantly prolonged atrial ERP in a concentration-dependent manner, whereas propofol and ketamine had no significant effect on atrial refractoriness. In contrast, ketamine caused a dose-dependent decrease in atrial CV, but propofol and thiopental had no significant effect on CV. Therefore, thiopental, ketamine, and propofol caused an increase, a decrease, and no change, respectively, in atrial wavelength. All anesthetics caused a concentration-dependent prolongation of the stimulus-to-His bundle interval, atrioventricular nodal ERP, and WCL. However, on an equimolar basis, significant differences in potencies were found. The concentrations of drug that caused a 20% increase in ERP (ERP20) and WCL (WCL20) for propofol, thiopental, and ketamine were 14 +/- 2 microM, 26 +/- 3 microM, and 62 +/- 11 microM, and 17 +/- 2 microM, 50 +/- 1 microM, and 123 +/- 19 microM (mean +/- SEM), respectively. Therefore, the rank order of potency for frequency-dependent atrioventricular nodal effects is propofol > thiopental > ketamine.


CONCLUSIONS
The authors' results indicate that propofol would be most effective at filtering atrial impulses during supraventricular tachydysrhythmias, whereas thiopental would be most effective at preventing atrial reentrant dysrhythmias. In contrast, ketamine may be most likely to promote atrial reentry while having minimal effect on atrioventricular nodal conduction.
Napolitano
C A
CA
Department of Anesthesiology, University of Florida College of Medicine, Gainesville 32610-0254, USA.
Raatikainen
M J
MJ
Martens
J R
JR
Dennis
D M
DM
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D016275:Atrial Function / Q000187:drug effects*; D001283:Atrioventricular Node / Q000187:drug effects*; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007649:Ketamine / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D015742:Propofol / Q000494:pharmacology; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects; D013617:Tachycardia, Supraventricular / Q000188:drug therapy*; D013874:Thiopental / Q000494:pharmacology
D018686:Anesthetics, Intravenous; D000889:Anti-Arrhythmia Agents; D007649:Ketamine; D013874:Thiopental; D015742:Propofol