Amiodarone chlorhydrate is a diiodated benzofuran derivative, and it is used to treat cardiac rhythm abnormalities. Hepatotoxicity is a relatively uncommon side effect of amiodarone, and symptomatic hepatic dysfunction occurs in fewer than 1% of the patients taking amiodarone. Cirrhosis is a rare complication that's been confirmed in 12 cases. Peripheral neuropathy occurs in 10% of patients taking aminodarone. We report here on an unusual case of amiodarone-induced hepatotoxicity and peripheral neurotoxicity. A 75 year old man with normal liver function was given amiodarone for treating his atrial fibrillation and heart failure. He developed nausea, vomiting, muscle weakness and wasting after 17.8 months therapy with amiodarone (400 mg orally once per day). Liver biopsy showed the presence of foam cells in the hepatic sinusoids and Mallory bodies in the periportal hepatocytes on light microscopy. Sural nerve biopsy showed demyelination, and nerve conduction studies showed mixed sensorimotor polyneuropathy. These observations show the necessity of monitoring the hepatic function and conducting neurologic examination of the patients treated with amiodarone.
Aged ; Amiodarone/*adverse effects ; Anti-Arrhythmia Agents/*adverse effects ; Hepatitis, Toxic/*etiology ; Humans ; Liver Cirrhosis/chemically induced ; Male ; Polyneuropathies/*chemically induced

OBJECTIVETo investigate the effect and potential mechanism of lysophosphatidic acid (LPA) and antiarrhythmic peptide (AAP10) on rabbit ventricular arrhythmia.

METHODSTwenty-four rabbits were randomly divided into three groups (n = 8 each): control group, LPA group and AAP10 + LPA group. Using arterially perfused rabbit ventricular wedge preparations, transmural ECG and action potentials from both endocardium and epicardium were simultaneously recorded in the whole process of all experiments with two separate floating microeletrodes. The incidence of ventricular arrhythmia post S1S2 stimulation was recorded. Protein levels of nonphosphorylated Cx43 and total Cx43 were evaluated by Western blot. The distribution of nonphosphorylated Cx43 was observed by confocal immunofluorescence microscopy.

RESULTSCompared with the control group, the QT interval, endocardial action potential duration, transmural repolarization dispersion (TDR) and incidence of ventricular arrhythmia were significantly increased and nonphosphorylated Cx43 expression was significantly upregulated in the LPA group. Compared with the LPA group, cotreatment with AAP10 can reduce the QT interval, endocardial action potential duration, TDR and incidence of ventricular arrhythmia (25.0% vs 62.5%, P < 0.01) and downregulate nonphosphorylated Cx43.

CONCLUSIONSLPA could promote the arrhythmia possibly by upregulating nonphosphorylated Cx43 and subsequent gap junction transmission inhibition. Gap junction enhancer AAP10 could attenuate the pro-arrhythmic effect of LPA probably by downregulating myocardial nonphosphorylated Cx43 expression.

Animals ; Anti-Arrhythmia Agents ; pharmacology ; Arrhythmias, Cardiac ; chemically induced ; metabolism ; physiopathology ; Connexin 43 ; metabolism ; Lysophospholipids ; adverse effects ; Oligopeptides ; pharmacology ; Rabbits

Amiodarone ; adverse effects ; Anti-Arrhythmia Agents ; adverse effects ; Arrhythmias, Cardiac ; drug therapy ; Corneal Diseases ; chemically induced ; Humans ; Male ; Middle Aged

For evaluating the effects of thoracic epidural anesthesia, with or without bilateral vagotomy, epinephrine-induced arrhythmias were studied in 31 rabbits anesthetized with 1 minimum alveolar concentration of enflurane. We divided the rabbits into 5 groups: Group I (epidural saline as control group; n=6), Group II (epidural lidocaine without vagotomy; n=6), Group III (intravenous lidocaine; n=7), Group IV (epidural saline with vagotomy; n=6), and Group V (epidural lidocaine with vagotomy; n=6). Using logdose protocol, epinephrine was infused at an initial rate of 0.67 microg/kg/min and increased by Exp[0.4] until arrhythmias occurred; if arrhythmias occurred at any of these doses, a smaller dose, divided by Exp[0.2], was tested. Arrhythmic dose of epinephrine was defined as the smallest infusion rate needed to produce four or more arrhythmias within 15 sec during epinephrine infusion. Arrhythmic dose of epinephrine and its plasma concentration in epidural lidocaine group were significantly higher than control (p<0.05). Similarity of results was also noted amongst the intravenous lidocaine group, vagotomy only group, and vagotomized epidural lidocaine group with respect to the control. These results suggest that thoracic epidural anesthesia raises the threshold for enflurane-epinephrine induced arrhythmias in rabbits and that this effect is eliminated by bilateral vagotomy.
Anesthesia, Epidural ; Anesthesia, Local ; Anesthetics, Inhalation ; Animal ; Anti-Arrhythmia Agents/therapeutic use* ; Arrhythmia/drug therapy* ; Arrhythmia/chemically induced ; Enflurane ; Epinephrine ; Female ; Hemodynamics ; Human ; Lidocaine/therapeutic use* ; Male ; Rabbits ; Vagotomy*

Acute amiodarone toxicity after a single dose of intravenous amiodarone is very rarely seen. We report the case of a 64-year-old Chinese man who presented with atrial fibrillation and fluid overload due to congestive cardiac failure. He was treated with a single bolus dose of intravenous amiodarone, after which he developed elevated serum transaminases, coagulopathy, thrombocytopenia and acute renal failure. His parameters returned to normal after 25 days and his recovery was uneventful.
Acute Kidney Injury ; chemically induced ; Amiodarone ; adverse effects ; Anti-Arrhythmia Agents ; adverse effects ; Atrial Fibrillation ; drug therapy ; Blood Coagulation Disorders ; chemically induced ; Heart Failure ; complications ; drug therapy ; Humans ; Male ; Middle Aged ; Thrombocytopenia ; chemically induced ; Transaminases ; blood ; Treatment Outcome

Patients who overdose on aconite can present with life-threatening ventricular arrhythmia. Aconite must be prepared and used with caution to avoid cardiotoxic effects that can be fatal. We herein describe a case of a patient who had an accidental aconite overdose but survived with no lasting effects. The patient had prepared Chinese herbal medication to treat his pain, which resulted in an accidental overdose of aconite with cardiotoxic and neurotoxic effects. The patient had ventricular tachycardia, bidirectional ventricular tachycardia and ventricular fibrillation. Following treatment with anti-arrhythmic medications, defibrillation and cardiopulmonary resuscitation, he made an uneventful recovery, with no further cardiac arrhythmias reported.
Aconitine ; poisoning ; Adult ; Anti-Arrhythmia Agents ; therapeutic use ; Cardiopulmonary Resuscitation ; Cardiotoxicity ; Drug Overdose ; Drugs, Chinese Herbal ; poisoning ; Electric Countershock ; Electrocardiography ; Humans ; Male ; Tachycardia ; chemically induced ; Tachycardia, Ventricular ; chemically induced ; Treatment Outcome ; Ventricular Fibrillation ; chemically induced

BACKGROUND/AIMS: Most current knowledge regarding amiodarone toxicity derives from clinical trials. This study was performed to investigate the incidence and risk factors of overall adverse effects of amiodarone in real-world practice using a large sample size. METHODS: Between January 1, 2000 and March 10, 2012, a total of 930 consecutive patients who had been treated with amiodarone for arrhythmia were reviewed retrospectively. An amiodarone-associated adverse event was considered in cases of discontinuation or drug dose reduction due to an unexpected clinical response. RESULTS: The mean daily dose of amiodarone was 227 +/- 126 mg, and the mean duration was 490 +/- 812 days. During the mean follow-up duration of 982 +/- 1,137 days, a total of 154 patients (16.6%) experienced adverse effects related to amiodarone, the most common being bradycardia or conduction disturbance (9.5%). Major organ toxicities in the thyroid (2.5%), liver (2.2%), eyes (0.6%), and lungs (0.3%) were rare. All patients recovered fully without complications after amiodarone discontinuation or dose reduction. The only independent predictor of adverse effects was the duration of amiodarone treatment (odds ratio, 1.21; 95% confidence interval, 1.03 to 1.41; p = 0.016, per year). CONCLUSIONS: Low-dose amiodarone is well tolerated in a real-world clinical population. Further studies with a prospective design are needed to confirm this finding.
Aged ; Amiodarone/administration & dosage/*adverse effects ; Anti-Arrhythmia Agents/administration & dosage/*adverse effects ; Arrhythmias, Cardiac/drug therapy ; Atrioventricular Block/chemically induced/epidemiology ; Bradycardia/chemically induced/epidemiology ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Republic of Korea ; Retrospective Studies ; Risk Factors

AIMTo investigate the antiarrhythmic effect of jumi (JM) extraction.

METHODSThe conventional antiarrhythmic methods were used.

RESULTSAdministration of JM extraction reduced the occurrence of ventricular fibrillation induced by chloroform in a dose-dependent manner in mice. Quinidine significantly decreased the number of ventricular premature beats and ventricular tachycardia, shortened the duration of arrhythmia in aconitine-treated rats. But JM extraction had no effect on aconitine-induced arrhythmia. Compared with control, arrhythmia score was lower in ischemia/reperfusion rats which pretreated with 2.0 g/kg of JM extraction.

CONCLUSIONJM extraction has obvious protection effects in chloroform- and ischemia-induced arrhythmia, but has no effect in aconitine-induced arrhythmia.

Animals ; Anti-Arrhythmia Agents ; therapeutic use ; Arrhythmias, Cardiac ; chemically induced ; drug therapy ; Female ; Male ; Mice ; Plant Extracts ; therapeutic use ; Rats ; Rats, Sprague-Dawley

AIMTo clarify mechanisms that the antiarrhythmic effects of matrine and berbamine are weaker than those of amiodarone and RP58866.

METHODSExperimental arrhythmic models were induced by aconitine, coronary artery ligation and electric stimulation in rats and rabbits. Whole-cell patch-clamp techniques were used to record IK1, IKr, IKs and Ito.

RESULTSMatrine and berbamine significantly increased the dose of aconitine for induction of ventricular premature and ventricular tachycardia in rats, decreased the number of arrhythmias induced by coronary artery ligation in rats and increased ventricular fibrillation threshold (VFT) induced by electric stimulation in rabbits, but the anti-arrhythmic potency of matrine and berbamine was lower than that of amiodarone and RP58866. The inhibitory actions of matrine and berbamine on IK1, IKr, IKs, Ito were lower than those of amiodarone and RP58866. The IC50 of matrine for IK1, IKr, IKs, Ito were (46 +/- 3), (32.9 +/- 1.2), (37 +/- 8) and (7.6 +/- 0.5) mol x L(-1), respectively. The IC50 of amiodarone for IK1, IKr, IKs, Ito were (21 +/- 5) , (3.7 +/- 0.7), (5.9 +/- 0.9) and (5.9 +/- 0.6) mol x L(-1), respectively.

CONCLUSIONThe inhibitory actions of matrine and berbamine on IK1, IKr, IKs, Ito were lower than those of amiodarone and RP58866, which might be the reason that the antiarrhythmic effects of matrine and berbamine were weaker than those of amiodarone and RP58866.

Aconitine ; Alkaloids ; pharmacology ; Amiodarone ; pharmacology ; Animals ; Anti-Arrhythmia Agents ; pharmacology ; Arrhythmias, Cardiac ; chemically induced ; physiopathology ; prevention & control ; Benzylisoquinolines ; pharmacology ; Chromans ; pharmacology ; Dogs ; Female ; Guinea Pigs ; Male ; Piperidines ; pharmacology ; Potassium Channels ; drug effects ; Quinolizines ; Rabbits ; Rats

AIMTo search for new compounds for the treatment of cardiovascular diseases by structural modification of cyclovirobuxine D.

METHODSAccording to rational drug design principle, a series of cyclovirobuxine D analogues were prepared, and their bioactivities were tested.

RESULTSTen new compounds were syntheized and confirmed by spectra.

CONCLUSIONEndurance lacking oxygen activity and antiarrhythmia effects of some analogues of cyclovirobuxine D were tested. Some compounds showed better activity than cyclovirobuxine D.

Anaerobic Threshold ; drug effects ; Animals ; Anti-Arrhythmia Agents ; chemical synthesis ; pharmacology ; Buxus ; chemistry ; Chloroform ; Drugs, Chinese Herbal ; chemical synthesis ; isolation & purification ; pharmacology ; Female ; Male ; Mice ; Molecular Structure ; Plants, Medicinal ; chemistry ; Random Allocation ; Ventricular Fibrillation ; chemically induced ; prevention & control