Premium
Acute effects of escalating doses of amiodarone in isolated guinea pig hearts
Author(s) -
BICER S.,
PATCHELL J. S.,
HAMLIN D. M.,
HAMLIN R. L.
Publication year - 2002
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1046/j.1365-2885.2002.00408.x
Subject(s) - amiodarone , qrs complex , qt interval , medicine , acute toxicity , chemistry , anesthesia , toxicity , cardiology , pharmacology , atrial fibrillation
Bicer, S., Patchell, J. S., Hamlin, D. M., Hamlin, R. L. Acute effects of escalating doses of amiodarone in isolated guinea pig hearts. J. vet Pharmacol. Therap. 25 , 221–226. 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 d P /d t max and d P /d t min 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 d P /d t max and d P /d t min at concentrations >10 –6 M did not achieve statistical significance. The putative therapeutic concentration of amiodarone is between 2 and 4 × 10 –6 M . In this study, at a concentration of 10 –6 M , only RR and d P /d t min tended to change, but they were not different from vehicle. Thus, amiodarone in this preparation has little potential for cardiac toxicity at therapeutic concentrations.