title: Acute effects of escalating doses of amiodarone in isolated guinea pig hearts.
abstract: Cardiac effects of escalating concentrations of amiodarone were determined on isolated perfused guinea pig hearts (Langendorff preparations). Spontaneously beating hearts were instrumented for the measurement of RR, PQ, QRS, QT and QTc durations (from a bipolar electrogram), and dP/dtmax and dP/dtmin from an isovolumetric left ventricular pressure curve. Ten hearts were exposed to escalating concentrations of amiodarone (10-7, 10-6, 10-5 and 10-4 M) in dimethyl sulfoxide (DMSO)/Krebs-Henseleit or to DMSO/Krebs-Henseleit (vehicle). Measurements were collected during the last minute of a 15-min concentration. Means of all parameters were compared by ANOVA with repeated measures design. When compared with vehicle, amiodarone prolonged QT and QTc durations at concentrations >10-6 M. The apparent lengthening of RR, PQ and QRS at concentrations >10-6 M did not achieve statistical significance. Similarly, the apparent decreases in dP/dtmax and dP/dtmin at concentrations >10-6 M did not achieve statistical significance. The putative therapeutic concentration of amiodarone is between 2 and 4 x 10-6 M. In this study, at a concentration of 10-6 M, only RR and dP/dtmin tended to change, but they were not different from vehicle. Thus, amiodarone in this preparation has little potential for cardiac toxicity at therapeutic concentrations.
authors.affiliation: QTest Laboratory, Columbus, Ohio, USA.
authors.forename: S
authors.initials: S
authors.lastname: Bicer
authors.forename: J S
authors.initials: JS
authors.lastname: Patchell
authors.forename: D M
authors.initials: DM
authors.lastname: Hamlin
authors.forename: R L
authors.initials: RL
authors.lastname: Hamlin
mesh_terms: D000638:Amiodarone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000662:veterinary; D006168:Guinea Pigs / Q000502:physiology*; D006329:Heart Conduction System / Q000502:physiology*; D008297:Male; D010477:Perfusion / Q000662:veterinary; D011897:Random Allocation
chemical_list: D000889:Anti-Arrhythmia Agents; D000638:Amiodarone