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Circ J 2018 Dec 23;83(1):41-51. Epub 2018 Oct 23.

Centro de Investigaciones Cardiovasculares, CONICET La Plata, Facultad de Ciencias Médicas, Universidad Nacional de La Plata.

Background: It has been shown that carvedilol and its non β-blocking analog, VK-II-86, inhibit spontaneous Ca release from the sarcoplasmic reticulum (SR). The aim of this study is to determine whether carvedilol and VK-II-86 suppress ouabain-induced arrhythmogenic Ca waves and apoptosis in cardiac myocytes. Methods and Results: Rat cardiac myocytes were exposed to toxic doses of ouabain (50 µmol/L). Read More

Ochsner J 2018 ;18(3):288-290

Department of Cardiology, University of Miami/JFK Medical Center, Atlantis, FL.

Background: Bidirectional ventricular tachycardia is a rare form of ventricular arrhythmia, characterized by a changing of the mean QRS axis of 180 degrees. Digitalis toxicity is the most common cause of bidirectional ventricular tachycardia; other causes include myocarditis, aconite toxicity, metastatic cardiac tumor, myocardial infarction, and cardiac channelopathies.

Case Report: A 73-year-old male with hypertension and a pacemaker implanted for sick sinus syndrome presented with a complaint of substernal chest pressure for several days. Read More

Drug Chem Toxicol 2018 Sep 21:1-7. Epub 2018 Sep 21.

d Department of Pharmacology and Toxicology , College of Medicine and Health Sciences, An-Najah National University , Nablus , Palestine.

Digoxin is a cardiac glycoside derived from the common foxglove digitalis purpurea and has been available for several centuries as a medicinal agent. Despite extensive patient experience over many years, there remains some controversy regarding the possibility that digoxin might have a deleterious effect on survival. This study was constructed to assess trends in digoxin toxicity research using well-established qualitative and quantitative bibliometric indicators. Read More

Biomed Pharmacother 2018 Sep 6;105:533-539. Epub 2018 Jun 6.

Department of Pharmacology, Faculty of Medicine, Assiut University, 71515 Assiut, Egypt.

Background: Toxic effects of digoxin may occur with normal therapeutic serum level. However, the underlying mechanisms are not fully understood. Nuclear factor kappa-B (NF-kB) is an important transcription factor in most organ systems and is often implicated in the harmful effects of cardiac injury. Read More

Am J Ophthalmol Case Rep 2018 Jun 2;10:233-235. Epub 2018 Mar 2.

Department of Ophthalmology, Columbia University Medical Center, New York, N.Y., United States.

Purpose: Since its report in one patient more than 70 years ago, digitalis-induced colored muscae volitantes have not surfaced again in the literature. We report here a case of digoxin induced colored floaters.

Observations: An 89-year-old man on 0. Read More

J Electrocardiol 2018 May - Jun;51(3):450-451. Epub 2018 Feb 8.

Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, United States. Electronic address:

This report describes a digitalis-induced regular fascicular ventricular tachycardia characterized by marked QRS alternans a manifestation not usually associated with this arrhythmia. The striking alternation of QRS configuration suggested alternating ventricular activation from either a single focus with two exits in distal branches of the left anterior fascicle or 2 different foci localized in the Purkinje-myocardial network of the left anterior fascicle. Read More

Am J Emerg Med 2018 Apr 8;36(4):735.e1-735.e3. Epub 2018 Jan 8.

Scientific Research and Education Department, Aerospace Center Hospital, 15 Yuquan Road, Beijing, 100049, People's Republic of China.

Bidirectional ventricular tachycardia (BVT) is a rare ventricular tachyarrhythmia. It is usually regular, demonstrating a beat-to-beat alternation in the QRS frontal axis that varies between -20° to -30° and +110°. The tachycardia rate is typically between 140 and 180 beats/min and the QRS is relatively narrow, with a duration of 120 to 150 ms. Read More

Nephron 2018 30;138(2):113-118. Epub 2017 Oct 30.

Department of Medicine E, Sheba Medical Center, Ramat Gan, Israel.

Background: Hypomagnesemia is a known predisposing condition for the appearance of digitalis toxicity. The detection of a genetic form of Mg urinary wasting with hypomagnesemia being caused by a mutation in the γ subunit (FXYD2) of the Na,K-ATPase, the pharmacological target of Digoxin, prompted us to investigate whether Digoxin administration increases urinary Mg excretion.

Methods: Two groups of subjects, with rapid atrial fibrillation, received intravenous Digoxin (n = 9) or verapamil (n = 8), for heart rate control. Read More

Curr Pharm Des 2017 ;23(34):5104-5114

Abant Izzet Baysal University, Faculty of Agricultural and Natural Sciences, Department of Horticulture, 14030 Bolu, Turkey.

The genus Digitalis L. containing species, commonly known as the "foxglove", is the main source of cardenolides, which have various pharmacological properties effective against certain pathological conditions including myocardial infarction, arterial hypertension, cardiac dysfunction, angina, and hypertrophy. Togehter with a prime effect of controlling the heart rhythm, many workers demonstrated that lanatoside C and some other cardiac glycosides are effective in several cancer treatments such as prostate and breast cancers. Read More

J Electrocardiol 2017 Nov - Dec;50(6):909-911. Epub 2017 Jul 12.

Division of Cardiovascular Medicine, Clemenceau Medical Center, Beirut, Lebanon. Electronic address:

A 38-year-old healthy male presented with vomiting and profuse diarrhea, associated with blurry and yellow coloration of the vision (xanthopsia). Laboratory workup was unremarkable, except for hyperkalemia (K 5.2 mEq/L) and mildly elevated troponin level 0. Read More

Basic Clin Pharmacol Toxicol 2017 Dec 10;121(6):526-530. Epub 2017 Jul 10.

Division of Electrophysiology, Department of Cardiovascular Medicine, University of Münster, Münster, Germany.

The I channel inhibitor ivabradine is recommended for treatment of heart failure but also affects potassium currents and thereby prolongs ventricular repolarization. The aim of this study was to examine the electrophysiological effects of ivabradine on digitalis-induced ventricular arrhythmias. Thirteen rabbit hearts were isolated and Langendorff-perfused. Read More

Clin Toxicol (Phila) 2017 Aug 2;55(7):670-673. Epub 2017 May 2.

b Department of Emergency Medicine , Chang Gung Memorial Hospital, Linkou Branch , Taoyuan , Taiwan.

Context: Accidental ingestion of foxglove (Digitalis purpurea) can cause significant cardiac toxicity. We report a patient who ingested foxglove mistaking it for comfrey and developed refractory ventricular arrhythmias. The patient died despite treatment with digoxin-specific antibody fragments (DSFab) and veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Read More

G Ital Cardiol (Rome) 2017 Feb;18(2):121-128

Dipartimento Cardiovascolare e Neurologico, Cardiologia Valdichiana, USL 8, Arezzo.

We performed a comprehensive review of the scientific literature on the use of digoxin in heart failure and atrial fibrillation. In congestive heart failure (CHF) there is only one randomized trial with a statistical sample sufficiently large. In this trial (DIG trial), which enrolled patients with systolic left ventricular dysfunction in sinus rhythm, digoxin had a neutral action on mortality and modestly reduced the overall need of hospitalization. Read More

Eur J Clin Pharmacol 2017 Jul 15;73(7):875-882. Epub 2017 Mar 15.

Centre for Clinical Toxicology and Pharmacology, Division of Internal Medicine, University Medical Centre Ljubljana, Zaloska cesta 7, 1000, Ljubljana, Slovenia.

Purpose: Drug-drug interaction (DDI) screening systems report potential DDIs. This study aimed to find the prevalence of probable DDI-related adverse drug reactions (ADRs) and compare the clinical usefulness of different DDI screening systems to prevent or warn against these ADRs.

Methods: A prospective cohort study was conducted in patients urgently admitted to medical departments. Read More

Acta Biomed 2017 01 16;87(3):353-357. Epub 2017 Jan 16.

University Hospital of Parma, Italy.

A 58 years healthy old woman was admitted to the Emergency Department (ED) with cardiac arrest due to ventricular fibrillation (VF). Appropriate cardiopulmonary resuscitation (CPR), multiple DC shocks and oro-tracheal intubation (OTI) were effective to induce recovery of spontaneous circulation (ROSC). After ROSC was achieved, the electrocardiogram (ECG) showed an idio-ventricular rhythm with atrioventricular dissociation. Read More

Rinsho Byori 2016 Dec;64(12):1390-1394

Antiarrhythmic drugs (AADs) can exhibit lethal adverse effects including proarrhythmia. To avoid these adverse effects, therapeutic drug monitoring (TDM) provides a therapeutic benefit. Recently, the Japanese Circulation Society and Japan TDM Society collaborated to do publish "Guidelines for TDM of Cardiovascular Drugs". Read More

Z Gerontol Geriatr 2018 Jan 22;51(1):41-47. Epub 2016 Nov 22.

Department of Internal Medicine and Geriatrics D, Sheba Medical Center, 5265601, Tel-Hashomer, Israel.

A systematic review was conducted for all published case reports on drug-induced torsade de pointes (TdP) in elderly (≥80 years) patients to study if the administration of the offending agent was reckless. Overall, 61 reports on drug-induced TdP in patients aged 80-97 years were included in the analysis. Non-modifiable risk factors for drug-induced TdP (e. Read More

Card Electrophysiol Clin 2016 12;8(4):753-764

University of California San Francisco Medical Center, 500 Parnassus Avenue, MUE 436, San Francisco, CA 94143-1354, USA.

Bidirectional ventricular tachycardia (BDVT) is a well-known phenomenon since it was first described in 1922. Various mechanisms have been proposed for BDVT, including digitalis toxicity, hypokalemia, Anderson-Tawil syndrome, acute myocarditis, and catecholaminergic polymorphic ventricular tachycardia. It is characterized by rapid, wide complex electrocardiogram pattern with alternating QRS morphology and axis. Read More

Eur J Pharmacol 2016 Dec 1;793:56-65. Epub 2016 Nov 1.

Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb, Croatia. Electronic address:

Bupivacaine toxicity following accidental overdose still lacks therapeutic solution. However, there are major arguments for testing BPC 157 against bupivacaine toxicity in vivo in rats, in particular, and then finally, in vitro. These are: the lack of any known BPC 157 toxicity, a lifesaving effect via the mitigation of arrhythmias in rats underwent hyperkalemia or digitalis toxicity, the elimination of hyperkalemia and arrhythmias in rats underwent succinylcholine toxicity and finally, the reduction of potassium-induced depolarization in vitro (in HEK293 cells) in severe hyperkalemia. Read More

Indian Heart J 2016 Sep 13;68 Suppl 2:S223-S225. Epub 2016 Apr 13.

Consultant Cardiologist, Mumbai, India.

"Digitalis toxicity, often candidly indexed as poisoning, has plagued the medical profession for over 200 years. The situation qualifies as a professional disgrace on the basis of three items: the situation persists, physicians are often slow to recognize it and, over the decades, writers have been harsh in their denunciation of fellow physicians when toxicity has occurred…." These are the opening remarks of an essay published in 1983 on the 2nd centenary of William Withering's 'magic potion from foxglove's extract for dropsy. Read More

Indian Pacing Electrophysiol J 2015 Nov-Dec;15(6):296-9. Epub 2016 Feb 23.

Department of Cardiology, Indira Gandhi Government General Hospital and Postgraduate Institute, Pondicherry, India.

Bidirectional ventricular tachycardia (BDVT) is a rare form of ventricular arrhythmia, characterized by changing QRS axis of 180 degrees. Digitalis toxicity is considered as commonest cause of BDVT; other causes include aconite toxicity, myocarditis, myocardial infarction, metastatic cardiac tumour and cardiac channelopathies. We describe a case of BDVT in a patient with Anderson-Tawil syndrome. Read More

Int J Cardiol 2016 Jul 14;215:519-20. Epub 2016 Apr 14.

Renmin Street, Jinzhou, Liaoning Province, 121001, China.

Int J Cardiol 2016 Apr 8;209:310-6. Epub 2016 Feb 8.

Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK. Electronic address:

Background: Digoxin is recommended in symptomatic heart failure patients with reduced ejection fraction (HF-REF) in sinus rhythm and refractory to other evidence-based therapy. Although HF-REF patients with diabetes have worse functional status than those without, the effects of digoxin have not been specifically evaluated according to diabetes status.

Methods: We examined the efficacy and safety of digoxin in HF-REF patients with and without diabetes in the Digitalis Investigation Group trial. Read More

CMAJ 2016 Jul 8;188(10):747-50. Epub 2016 Feb 8.

Departments of Medicine (Janssen, Ovakim) and Emergency Medicine (Berg), University of British Columbia; British Columbia Drug and Poison Information Centre (Ovakim), Vancouver, BC.

Toxicol In Vitro 2016 Apr 17;32:138-45. Epub 2015 Dec 17.

Department of Pharmacology and Toxicology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, The Netherlands. Electronic address:

Digitalis-like compounds (DLCs), the ancient medication of heart failure and Na,K-ATPase inhibitors, are characterized by their toxicity. Drug-drug interactions (DDIs) at absorption and excretion levels play a key role in their toxicity, hence, knowledge about the transporters involved might prevent these unwanted interactions. In the present study, the transport of fourteen DLCs with human P-glycoprotein (P-gp; ABCB1) was studied using a liquid chromatography-mass spectrometry (LC-MS) quantification method. Read More

Food Funct 2016 Feb;7(2):798-804

Novastell, F-27150 Etrépagny, France.

Docosahexaenoic acid (DHA) might prevent heart failure or optimise drug treatments by improving cardiac contraction. We investigated whether DHA-enriched avian glycerophospholipids (GPL-DHA) exert cardioprotection in ouabain-treated rats after 4 weeks of dietary supplementation with 10, 35 or 60 mg DHA per kg body weight versus none (DHA10, DHA35, DHA60 and control groups, respectively). The contractile responsiveness to different doses of ouabain (10(-7) to 10(-4) M), ouabain intoxication (at 3 × 10(-4) M), and relative variations in cardiac energy metabolism were determined using (31)P NMR in isolated perfused rat hearts. Read More

J Assoc Physicians India 2015 May;63(5):79-81

Cardiac glycosides are widely available in botanic products and other naturally occurring substances worldwide. Accidental consumption of it leads to digitalis toxicity with varied systemic manifestations. We describe a case of consumption of extract of leaves of the Indian rubber vine plant (Crytostegia grandiflora) which led to gastrointestinal, cardiac, electrolyte, and hematological disturbances. Read More

J Pharm Biomed Anal 2015 Nov 13;115:169-73. Epub 2015 Jul 13.

Pharmaceutical Laboratory, Health Sciences Authority, 11 Outram Road, 169078, Singapore. Electronic address:

In this study, an LC-MS/MS EPI method was developed for simultaneous determination of 32 toxic natural substances in herbal products. The analytes include aconite alkaloids, lobelia alkaloids, solanaceous alkaloids, digitalis steroid glycosides, strychnine, tetrahydropalmatine etc. They werecommonly used in herbal products. Read More

Gynecol Oncol 2015 Sep 13;138(3):735-40. Epub 2015 Jul 13.

European Competence Center for Ovarian Cancer (EKZE), Department of Gynecology, Charité - University Medicine of Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany. Electronic address:

Background: Ovarian cancer is usually a cancer of the older age group. Comorbidities and comedications increase with rising age. Aim of this study was to evaluate association of comorbidity and comedication with grade III/IV toxicities and prior cessation of chemotherapy in ovarian cancer patients. Read More

Anatol J Cardiol 2015 25;15(12):970-5. Epub 2014 Dec 25.

Department of Pediatric Cardiology, Malatya State Hospital, Malatya-Turkey.

Objective: Digitalis preparations are commonly used by children and adults with heart diseases worldwide, although excessive doses may cause cardiac effects. The aim of the study is to evaluate the antiarrhythmic effect of Crataegus oxyacantha extract on digoxin-induced arrhythmias in anesthetized Wistar rats.

Methods: Control and experimental groups were evaluated for arrhythmias induced by digoxin. Read More

Ann Indian Acad Neurol 2015 Jan-Mar;18(1):6-9

Department of Neurology, Bangur Institute of Neurosciences, Kolkata, West Bengal, India.

Vincent Van Gogh is one of the most celebrated creative artists of all time. All his life, he was afflicted by some kind of neurological or psychiatric disorder, which remains a mystery even today. Many historians and his personal physicians believe that he suffered from epilepsy while others felt that he was affected by Ménière's disease. Read More

Int J Cardiol 2015 Feb 13;181:176-8. Epub 2014 Dec 13.

Department of General and Interventional Cardiology, Hamburg University Heart Center, Hamburg, Germany.

Am J Med 2015 Mar 26;128(3):257-9. Epub 2014 Nov 26.

Division of Cardiovascular Medicine, Department of Internal Medicine, University of California Davis Medical Center, Sacramento. Electronic address:

J Vet Emerg Crit Care (San Antonio) 2015 Mar-Apr;25(2):210-25. Epub 2014 Nov 26.

From the Animal Emergency Center and Specialty Services, Glendale, WI 52309.

Objective: To review magnesium physiology including absorption, excretion, and function within the body, causes of magnesium abnormalities, and the current applications of magnesium monitoring and therapy in people and animals.

Etiology: Magnesium plays a pivotal role in energy production and specific functions in every cell in the body. Disorders of magnesium can be correlated with severity of disease, length of hospital stay, and recovery of the septic patient. Read More

Eur J Pharmacol 2014 Dec 28;744:18-27. Epub 2014 Sep 28.

Department of Pharmacology and Toxicology 149, Radboud University Medical Centre, Radboud Institute for Molecular Life Sciences, PO Box 9101, 6500 HB Nijmegen, The Netherlands. Electronic address:

Digitalis-like compounds (DLCs), such as digoxin and digitoxin that are derived from digitalis species, are currently used to treat heart failure and atrial fibrillation, but have a narrow therapeutic index. Drug-drug interactions at the transporter level are frequent causes of DLCs toxicity. P-glycoprotein (P-gp, ABCB1) is the primary transporter of digoxin and its inhibitors influence pharmacokinetics and disposition of digoxin in the human body; however, the involvement of P-gp in the disposition of other DLCs is currently unknown. Read More

Indian Heart J 2014 Jul-Aug;66(4):466-9. Epub 2014 Jun 23.

Attending Physician, Good Samaritan Heart and Vascular Hospital, Dayton, OH, USA.

Bidirectional ventricular tachycardia (BVT) is a rare variety of tachycardia with morphologically distinct presentation: The QRS axis and/or morphology is alternating in the frontal plane leads. Since its original description in association with digitalis,(1) numerous cases of this fascinating tachycardia with disparate etiologies and mechanisms have been postulated. We report a patient with BVT in association with non-ST elevation myocardial infarction and severe cardiomyopathy in the absence of digoxin toxicity. Read More

J La State Med Soc 2014 May-Jun;166(3):123-4. Epub 2014 Jun 10.

Former Fellow in the Sections of Cardiology, Departments of Medicine, Louisiana State University Health Sciences Center and the Interim LSU Hospital, New Orleans.

Cochrane Database Syst Rev 2014 Apr 28(4):CD002901. Epub 2014 Apr 28.

Department of Medicine, University of Washington, Seattle, WA, USA.

Background: Digitalis glycosides have been in clinical use for the treatment of heart failure (HF) for longer than 200 years. In recent years, several trials have been conducted to address concerns about their efficacy and toxicity.

Objectives: To examine the effectiveness of digitalis glycosides in treating HF in patients with normal sinus rhythm. Read More

Clin Pharmacokinet 2014 May;53(5):397-407

Laboratory of Applied Pharmacokinetics, Keck School of Medicine, University of Southern California, Children's Hospital of Los Angeles, MS # 51, 4650 Sunset Blvd, Los Angeles, CA, 90027, USA,

This report examined the role of digitalis pharmacokinetics in helping to guide therapy with digitalis glycosides with regard to converting atrial fibrillation (AF) or flutter to regular sinus rhythm (RSR). Pharmacokinetic models of digitoxin and digoxin, containing a peripheral non-serum effect compartment, were used to analyze outcomes in a non-systematic literature review of five clinical studies, using the computed concentrations of digitoxin and digoxin in the effect compartment of these models in an analysis of their outcomes. Four cases treated by the author were similarly examined. Read More

BMJ Case Rep 2013 Aug 13;2013. Epub 2013 Aug 13.

Department of Medicine, Kasturba Medical College, Manipal University, Manipal, Karnataka, India.

We report the case of a 65-year-old woman presenting with recurrent vomiting for 3 days. She had been previously diagnosed with an atrial septal defect and was on treatment with diuretics and digoxin for paroxysmal supraventricular tachycardia. The clinical examination was consistent with an atrial septal defect with severe pulmonary hypertension. Read More

Am J Hypertens 2013 Nov 22;26(11):1269-72. Epub 2013 Jul 22.

National Institute on Aging, National Institutes of Health, Baltimore, MD;

Background: Immunoneutralization of elevated circulating levels of endogenous digitalis-like Na/K-ATPase inhibitors (i.e. cardiotonic steroids (CTS)) represents a novel approach in the treatment of preeclampsia (PE). Read More

G Ital Cardiol (Rome) 2013 Jun;14(6):445-55

Dividione di Cardiologia, Ospedale SS, Trinità, ASI, NO, Borgomanero, Milano.

Accidental or deliberate ingestion of poisonous herbs has become an increasingly common phenomenon over the last years. From existing literature data and case reports from emergency room visits or poison control centers, an overview is presented of the potential cardiotoxic manifestations following intoxication by wild herbal plants of the territory. The effects of the consumption of cardiac glycoside-containing plants (e. Read More

J Coll Physicians Surg Pak 2013 May;23(5):347-9

Department of Cardiology, National Institute of Cardiovascular Diseases, Karachi.

A 45 years old male presented to the emergency department with palpitations, headache and apprehension. His electrocardiogram revealed bidirectional ventricular tachycardia. He remained vitally stable and responded to intravenous beta-blocker. Read More

Geriatr Psychol Neuropsychiatr Vieil 2012 Dec;10(4):355-63

Unité gériatrique aiguë, Groupe hospitalier Pitié-Salpêtrière-Charles Foix, AP-HP, Paris, France, UFR de médecine Pierre et Marie Curie, Université Paris 6, France.

The indications for digoxin are currently limited to rare cases of heart failure and/or atrial fibrillation. Its use should be even more rare in geriatrics its pharmacological characteristics, associated with age-related changes and comorbidities, particularly increase the risk of digoxin poisoning in the elderly. However, at least a third of aged patients suffering from heart failure and/or atrial fibrillation is treated by digitalis. Read More

Toxicol Sci 2013 Feb 26;131(2):502-11. Epub 2012 Oct 26.

Department of Pharmacology and Toxicology, 149, Radboud University Nijmegen Medical Centre, Nijmegen Centre for Molecular Life Sciences, PO Box 9101, 6500 HB Nijmegen, The Netherlands.

Digitalis-like compounds (DLCs), or cardiac glycosides, are produced and sequestered by certain plants and animals as a protective mechanism against herbivores or predators. Currently, the DLCs digoxin and digitoxin are used in the treatment of cardiac congestion and some types of cardiac arrhythmia, despite a very narrow therapeutic index. P-glycoprotein (P-gp; ABCB1) is the only known ATP-dependent efflux transporter that handles digoxin as a substrate. Read More

Ann Noninvasive Electrocardiol 2012 Oct 13;17(4):405-8. Epub 2012 Aug 13.

Department of Cardiology and Electrophysiology, Hartford Hospital, University of Connecticut, Hartford, CT, USA.

Bidirectional ventricular tachycardia (BVT) is an uncommon type of polymorphic ventricular tachycardia (PVT) with alternating polarity of the QRS complex most commonly described digitalis toxicity. Recent data has demonstrated the possible molecular basis of this electrocardiographic phenomenon. To our knowledge this is the first reported case of BVT in a patient with orthotopic cardiac transplantation and coronary allograft vasculopathy. Read More