1 The electrophysiological e ects of dronedarone, a new nonionidated analogue of amiodarone were studied after chronic and acute administration in dog Purkinje ®bres, papillary muscle and isolated ventricular myocytes, and compared with those of amiodarone by applying conventional microelectrode and patch-clamp techniques. 2 Chronic treatment with dronedarone (2625 mg 71 kg 71 day p.o. for 4 weeks), unlike chronic administration of amiodarone (50 mg 71 kg 71 day p.o. for 4 weeks), did not lengthen signi®cantly the QTc interval of the electrocardiogram or the action potential duration (APD) in papillary muscle. After chronic oral treatment with dronedarone a small, but signi®cant use-dependent V max block was noticed, while after chronic amiodarone administration a strong use-dependent V max depression was observed. 3 Acute superfusion of dronedarone (10 mM), similar to that of amiodarone (10 mM), moderately lengthened APD in papillary muscle (at 1 Hz from 239.6+5.3 to 248.6+5.3 ms, n=13, P50.05), but shortened it in Purkinje ®bres (at 1 Hz from 309.6+11.8 to 287.1+10.8 ms, n=7, P50.05). 4 Both dronedarone (10 mM) and amiodarone (10 mM) superfusion reduced the incidence of early and delayed afterdepolarizations evoked by 1 mM dofetilide and 0.2 mM strophantidine in Purkinje ®bres. 5 In patch-clamp experiments 10 mM dronedarone markedly reduced the L-type calcium current (76.5+0.7 %, n=6, P50.05) and the rapid component of the delayed recti®er potassium current (97+1.2 %, n=5, P50.05) in ventricular myocytes. 6 It is concluded that after acute administration dronedarone exhibits e ects on cardiac electrical activity similar to those of amiodarone, but it lacks the`amiodarone like' chronic electrophysiological characteristics.
SCS appears to enhance parasympathetic activity, mediated via the vagus. This may have implications for use of thoracic SCS to treat chronic angina and perhaps prevent sudden cardiac death.
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