Methoxyflurane anesthesia augments the chronotropic and dromotropic effects of verapamil.
BACKGROUND
Inhalation anesthetics have been shown to have electrical suppressant effects on excitable membranes such as the cardiac conduction system. Therefore, the anesthetized patient or laboratory animal may respond differently to cardiac drugs when compared with their conscious counterparts. The purpose of this study was to assess the effects of anesthesia with methoxyflurane (MF) on the dromotropic and chronotropic effects of verapamil (VER) in the rat.


METHODS
A lead I ECG was measured using subcutaneous electrodes placed both axilli and over the xyphoid process in male Sprague-Dawley rats. Dromotropic effect was measured using the PR-interval which indicated the electrical spread across the atria to the AV-node and chronotropic effects were determined using RR-interval. A total of six animals were randomized to receive 10 mg/kg s.c. of verapamil in the presence or absence of general anesthesia containing methoxyflurane. In addition, PR-interval and RR-intervals were determined in the presence of only methoxyflurane and at rest without any drug exposure. The time for the ECG to normalize after exposure to methoxyflurane and/or verapamil was also determined.


RESULTS
Exposure to verapamil alone resulted in a 5% prolongation in PR-interval and 6% prolongation in RR-interval. Methoxyflurane alone had a larger effect than verapamil demonstrating a 14.5% prolongation in PR-interval and a 12.3% in RR-interval which was statistically significant. The combination of MF + VER resulted in a synergistic prolongation in PR-interval to 28. 7% while the effect on RR-interval was additive with an increase to 17.6%. The time for the ECG to normalize after exposure to VER, MF and VER + MF was 37.5 15.1 min, 69.8 5.3 min, and 148.5 +/- 6.6 min respectively.


CONCLUSIONS
General anesthesia with MF enhances the dromotropic and chronotropic effect of VER. This should be considered when MF-anesthesia is used in experimental procedure.
Jamali
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F
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada. fjamali@pharmacy.ualberta.ca
Mayo
P R
PR
D000768:Anesthesia, General; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001283:Atrioventricular Node / Q000187:drug effects; D004357:Drug Synergism; D004562:Electrocardiography / Q000187:drug effects; D006325:Heart Atria / Q000187:drug effects; D006329:Heart Conduction System / Q000187:drug effects*; D008297:Male; D008733:Methoxyflurane / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014700:Verapamil / Q000494:pharmacology*
D018685:Anesthetics, Inhalation; D000889:Anti-Arrhythmia Agents; D008733:Methoxyflurane; D014700:Verapamil