title: Additive cardiac depression by volatile anesthetics in isolated hearts after chronic amiodarone treatment.
abstract: Some patients undergoing general anesthesia may be chronically receiving the antidysrhythmic drug amiodarone. The half-life of this drug is very long and it may not be advisable or possible to discontinue its administration prior to anesthesia. We examined depressant effects of three volatile anesthetics in hearts isolated from guinea pigs chronically treated with amiodarone. Hearts were isolated and perfused retrogradely through the aorta with oxygenated Krebs-Ringer solution at 37 degrees C at constant pressure. Variables measured in 26 hearts were heart rate (HR), atrioventricular, intraatrial, and intraventricular conduction times (AVCT, IACT, IVCT) during pacing at 240 bpm, coronary flow, and left ventricular pressure (LVP). Amiodarone (20 mg intraperitoneally) or placebo (Group 1) was given once daily for 1 (Group 2) or 4 (Group 3) wk. Cardiac tissue concentrations of amiodarone were similar (12.1 micrograms/g wet weight) in hearts in Groups 2 and 3 but serum levels were twice as high in hearts in Group 3 as in Group 2 (0.33 vs 0.17 microgram/mL). Before anesthetic exposure, all variables for hearts in Group 2 were not significantly different from those in Group 1. Significantly, for hearts in Group 3, compared to those in Group 1, HR was slower (-14%), conduction times were longer (IACT + 5 ms, IVCT + 4 ms, AVCT + 9 ms), coronary flow was higher (+23%), and LVP was lower (-12%). After control measurements, hearts were exposed to 0.5 and 1 minimum alveolar anesthetic concentration (MAC) halothane, enflurane, and isoflurane in random order.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226, USA.
authors.forename: R T
authors.initials: RT
authors.lastname: Rooney
authors.forename: J
authors.initials: J
authors.lastname: Marijic
authors.forename: K A
authors.initials: KA
authors.lastname: Stommel
authors.forename: Z J
authors.initials: ZJ
authors.lastname: Bosnjak
authors.forename: A
authors.initials: A
authors.lastname: Aggarwal
authors.forename: J P
authors.initials: JP
authors.lastname: Kampine
authors.forename: D F
authors.initials: DF
authors.lastname: Stowe
mesh_terms: D000638:Amiodarone / Q000493:pharmacokinetics / Q000494:pharmacology*; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004737:Enflurane / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006221:Halothane / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D006329:Heart Conduction System / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: D018685:Anesthetics, Inhalation; D004737:Enflurane; D007530:Isoflurane; D000638:Amiodarone; D006221:Halothane