Opposite effects of iv amiodarone on cardiovascular vagal and sympathetic efferent activities in rats.

It is unknown whether amiodarone exerts a direct central action on the cardiovascular autonomic nervous system. This study was designed to evaluate the effects of acute amiodarone administration on vagal and sympathetic efferent nerve discharges. Experiments were carried out in 25 decerebrate unanesthetized rats. In one group, vagal activity was recorded from preganglionic fibers isolated from the cervical vagus nerve. In another group, sympathetic recordings were obtained from fibers isolated from the cervical sympathetic trunk in intact conditions or after barodenervation. Recordings were performed before and for 60 min after amiodarone (50 mg/kg iv) administration. In all groups, amiodarone induced bradycardia and hypotension. Vagal activity increased immediately, reaching a significant difference after 20 min (260 +/- 131% from 16.4 +/- 3.3 spikes/s) and was unmodified by the barodenervation. At difference, sympathetic activity after an initial and short-lasting increase (150 +/- 83% from 24.8 +/- 5.7 spikes/s) began to decrease significantly after 20 min (36 +/- 17%) throughout the experiment. The initial increase in sympathetic activity was not observed in barodenervated animals. These changes in vagal and sympathetic activity could play an important role in contributing to the antiarrhythmic action of amiodarone.

[1]  D. Vergani,et al.  Heart rate variability and early recurrence of atrial fibrillation after electrical cardioversion. , 2001, Journal of the American College of Cardiology.

[2]  W. A. Murray,et al.  Amiodarone for resuscitation after out-of-hospital cardiac arrest due to ventricular fibrillation. , 1999, The New England journal of medicine.

[3]  Y. Hara,et al.  Inhibitory effect of amiodarone on the muscarinic acetylcholine receptor-operated potassium current in guinea pig atrial cells. , 1996, The Journal of pharmacology and experimental therapeutics.

[4]  M. Janse,et al.  Effect of prophylactic amiodarone on mortality after acute myocardial infarction and in congestive heart failure: meta-analysis of individual data from 6500 patients in randomised trials , 1997, The Lancet.

[5]  R. Summers,et al.  The effects of amiodarone, an alpha and beta receptor antiagonist, on adrenergic transmission in the cat spleen. , 1976, Biochemical pharmacology.

[6]  W. Lewis Evaluation and treatment strategies in patients at high risk of sudden death post myocardial infarction. , 1997, Clinical cardiology.

[7]  E. Riva,et al.  Pharmacokinetics of Amiodarone in Rats , 1982, Journal of cardiovascular pharmacology.

[8]  P. Kowey,et al.  Intravenous amiodarone. , 1997, Journal of the American College of Cardiology.

[9]  P. Schwartz,et al.  Single cardiac vagal fiber activity, acute myocardial ischemia, and risk for sudden death. , 1991, Circulation research.

[10]  A Malliani,et al.  Neural mechanisms in life-threatening arrhythmias. , 1980, American heart journal.

[11]  J. Bigger,et al.  Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction , 1998, The Lancet.

[12]  Murthy Vs,et al.  Antiarrhythmic drugs and the modulation of autonomic control of heart rate in rabbits. , 1986 .

[13]  J Toyama,et al.  Amiodarone: ionic and cellular mechanisms of action of the most promising class III agent. , 1999, The American journal of cardiology.

[14]  R. Candinas,et al.  Role of the sympathetic nervous system in the genesis of ventricular arrhythmia. , 1990, Circulation.

[15]  P Coumel,et al.  Autonomic Influences in Atrial Tachyarrhythmias , 1996, Journal of cardiovascular electrophysiology.

[16]  M. Lesh,et al.  Autonomic nervous system and sudden cardiac death. , 1996, Journal of the American College of Cardiology.

[17]  T. N. James,et al.  Acute effects of amiodarone upon the canine sinus node and atrioventricular junctional region. , 1983, The Journal of clinical investigation.

[18]  H L Greene,et al.  Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. , 1991, The New England journal of medicine.

[19]  N. El-Sherif,et al.  Hypotensive Action of Commercial Intravenous Amiodarone and Polysorbate 80 in Dogs , 1982, Journal of cardiovascular pharmacology.

[20]  S. Connolly Evidence-based analysis of amiodarone efficacy and safety. , 1999, Circulation.

[21]  Alberto Malliani,et al.  Principles of Cardiovascular Neural Regulation in Health and Disease , 2012, Basic Science for the Cardiologist.

[22]  A. Dart,et al.  Sympatholytic action of intravenous amiodarone in the rat heart. , 1995, Circulation.

[23]  P. Schwartz,et al.  Autonomic nervous system and sudden cardiac death. Experimental basis and clinical observations for post-myocardial infarction risk stratification. , 1992, Circulation.

[24]  G. Schreiber,et al.  Interaction of the antiarrhythmic drug amiodarone with the muscarinic receptor in rat heart and brain. , 1984, Journal of cardiovascular pharmacology.

[25]  V. Murthy,et al.  Antiarrhythmic drugs and the modulation of autonomic control of heart rate in rabbits. , 1986, Federation proceedings.

[26]  R. Summers,et al.  The effects of amiodarone, an α and β receptor antagonist, on adrenergic transmission in the cat spleen , 1976 .