NEGATIVE INOTROPIC EFFECTS OF AMIODARONE ON ISOLATED GUINEA-PIG PAPILLARY-MUSCLE

Study objective - The aim of the study was to investigate the inotropic effects on isolated papillary muscle of acute and chronic exposure to amiodarone.Design - Papillary muscles were obtained from untreated and amiodarone pretreated Guinea pigs, and tension recording and conventional glass microelectrode techniques were used to assess the effects of amiodarone.Subjects - Guinea pigs of either sex weighing 300-500 g were used: 65 untreated and 18 amiodarone pretreated (20 mg·kg-1·d-1 for 32-jan weeks).Measurements and results - Acute amiodarone exposure (4·4 × 10-6 - 1.1 × 10-3 mol·litre-1) caused a concentration dependent negative inotropic effect, which was also frequency dependent (0.1 - 5 Hz), with greater effect at higher stimulation frequencies. Time to peak tension and resting tension increased, while rate of development and relaxation of twitch contraction were slower. Amiodarone caused a dose dependent depression or abolition of slow response action potentials and of contraction in both untreated and amiodarone pretreated specimens. In amiodarone pretreated muscle, contractile forces did not differ significantly from control preparations. Chronic exposure to amiodarone attenuated the negative inotropic effects of acute amiodarone superfusion.Conclusions - The negative inotropic action of amiodarone may reflect a decrease in Na+ influx via Na- channels and/or Ca2+ influx via Ca2+ channels, and/or an impairment of Ca2+ sequestration, alone or in combination. The differences in contractile response in relation to acute and chronic amiodarone exposure may be relevant to clinical actions of amiodarone.