Cardiotoxic Effects of Micrurus surinamensis (Cuvier, 1817) Snake Venom.

Micrurus surinamensis is a coral snake from the Elapidae family of wide distribution in Amazonia Forest. Its venom contains neurotoxins that induce muscular and respiratory paralysis; however, its cardiovascular action is not yet characterized. The aim of this study was to investigate the cardiotoxic effects caused by M. surinamensis poisoning in rodents. Twelve guinea pigs (Cavia porcellus) were distributed in two groups (n = 6) named as control and envenomed. The control group received 0.2 ml of PBS/BSA via intramuscular injection (IM), while envenomed animals received 0.75 µg of venom per g of body weight, also via IM. Electrocardiographic examination (ECG) and biochemical serum tests were conducted before and 2 h after inoculation. ECG of the envenomed animals revealed severe progressive arrhythmias including atrioventricular block, supraventricular, and ventricular extrasystoles. Serum biochemistry showed significant increase in CK, CK-MB, and LDH enzymes corroborating the skeletal and cardiac muscle damage. Myonecrosis and degeneration were observed in both skeletal and heart muscle; nevertheless, transmission electron microscopy revealed cardiac muscle fibers fragmentation. In conclusion, M. surinamensis venom has a potent cardiotoxic activity eliciting arrhythmogenic effects and heart damage after only 2 h of envenomation.

Cannabidiol Interacts Significantly with Everolimus-Report of a Patient with Tuberous Sclerosis Complex.

A 6.5-year-old female patient with a TSC2 mutation had been given everolimus (EVE) for 3 years for pharmacoresistant focal epilepsy and for life-threatening, severe ventricular dysrhythmia. EVE had been started with daily dose of 0.15 mg/kg/day and was increased up to 0.6 mg/kg/day. Target blood trough levels of around 9 µg/L had been documented. Although EVE therapy revealed no effect on seizure activity, cardiac rhythm normalized completely. Thus, EVE was reduced to a dose of 0.3 mg/kg/day leading to stable blood trough levels of 4 to 5 µg/L. Due to refractory tonic seizures with a frequency of 1 to 4 per day, we initiated cannabidiol (CBD) treatment, raising it to a daily dose of 200 mg. After 6 weeks, the EVE blood trough levels rose to 12.0 µg/L. Although we halved the EVE dose, her EVE blood trough level continued increasing up to 16.0 µg/L.The CBD dose was increased to 500 mg/day (20.4 g/kg/day), but EEG parameters and seizures failed to respond. Serum concentrations of EVE were unstable under the co-medication with CBD. Depending on the CBD dose, they varied between 1.7 and 12.3 µg/L, while EVE was always administered at the same dose.Although never before reported, CBD and EVE appear to interact, due to the metabolic pathway through CYP 450 3A4. Although we detected no side effects in our patient, we strongly recommend drug monitoring using the combination of CBD with EVE to prevent harmful overdosing.

Case report: electrical storm during induced hypothermia in a patient with early repolarization.

BACKGROUND: Population based studies showed an association of early repolarization in the electrocardiogram (ECG) and a higher rate of sudden cardiac death presumably due to ventricular fibrillation. The triggers for ventricular fibrillation in patients with early repolarization are not fully understood. CASE PRESENTATION: We describe the case of a young patient with a survived ventricular fibrillation arrest while asleep followed by multiple episodes of recurrent ventricular fibrillation. The admission ECG showed an early repolarization pattern with substantial J-point elevation in most of the ECG-leads. After initiation of a hypothermia protocol, the patient developed an electrical storm with multiple ventricular fibrillation episodes requiring multiple cardioversions. Intravenous isoproterenol infusion successfully suppressed the malignant arrhythmia. CONCLUSION: Hypothermia appears proarrhythmic in patients with early repolarization and may trigger ventricular fibrillation. This knowledge is particularly important when initiating temperature management protocols in patients after a survived cardiac arrest. During the acute phase of an early repolarization associated electrical storm, isoproterenol is the most effective treatment suppressing the ventricular fibrillation-inducing premature ventricular complexes at higher heart rates.

Premature ventricular contractions associated with isotretinoin use

Abstract Isotretinoin has been considered a unique drug for acne treatment. However, it is associated with numerous adverse effects. Isotretinoin can trigger premature ventricular contractions. This report describes a 33-year-old-woman who presented with palpitations for 1 week while undergoing 1-month isotretinoin treatment for mild-moderate facial acne. An electrocardiogram and Holter monitoring showed premature ventricular contractions during isotretinoin (Roaccutane, Roche) treatment. Isotretinoin-related premature ventricular contractions were strongly suggested in this case due to the existence of documented premature ventricular contractions on electrocardiograms and the disappearance of these premature ventricular contractions two weeks after termination of the treatment To the authors' knowledge, there has been 1 reported case of premature ventricular contractions linked to isotretinoin use; this report describes a second such case.

Ventricular arrhythmias induced by long-term use of ephedrine in two competitive athletes.

Ephedrine is a sympathomimetic substance used by sportsmen as a doping substance because of its stimulating and slimming effects. We report two cases of ventricular arrhythmias induced by abuse of ephedrine in two competitive athletes. Endomyocardial biopsies guided by electroanatomic mapping revealed contraction-band necrosis, a myocardial injury frequently observed in cases of catecholamine excess. Our cases suggest that long-term abuse of ephedrine may result in myocardial damage, and that these structural alterations may promote areas of slow conduction favoring re-entrant ventricular tachyarrhythmias and a long-lasting risk of ventricular arrhythmias.

ß1-Adrenoceptor blocker aggravated ventricular arrhythmia.

OBJECTIVES: To assess the impact of ß1 -adrenoceptor blockers (ß1 -blocker) and isoprenaline on the incidence of idiopathic repetitive ventricular arrhythmia that apparently decreases with preprocedural anxiety. METHODS: From January 2010 to July 2012, six patients were identified who had idiopathic ventricular arrhythmias that apparently decreased (by greater than 90%) with preprocedural anxiety. The number of ectopic ventricular beats per hour (VPH) was calculated from Holter or telemetry monitoring to assess the ectopic burden. The mean VPH of 24 hours from Holter before admission (VPH-m) was used as baseline (100%) for normalization. ß1 -Blockers, isoprenaline, and/or aminophylline were administrated successively on the ward and catheter lab to evaluate their effects on the ventricular arrhythmias. RESULTS: Among 97 consecutive patients with idiopathic ventricular arrhythmias, six had reduction in normalized VPHs in the hour before the scheduled procedure time from (104.6 ± 4.6%) to (2.8 ± 1.6%) possibly due to preprocedural anxiety (P < 0.05), then increased to (97.9 ± 9.7%) during ß1 -blocker administration (P < 0.05), then quickly reduced to (1.6 ± 1.0%) during subsequent isoprenaline infusion. Repeated ß1 -blocker quickly counteracted the inhibitory effect of isoprenaline, and VPHs increased to (120.9 ± 2.4%) from (1.6 ± 1.0%; P < 0.05). Isoprenaline and ß1 -blocker showed similar effects on the arrhythmias in catheter lab. CONCLUSIONS: In some patients with structurally normal heart and ventricular arrhythmias there is a marked reduction of arrhythmias associated with preprocedural anxiety. These patients exhibit a reproducible sequence of ß1 -blocker aggravation and catecholamine inhibition of ventricular arrhythmias, including both repetitive ventricular premature beats and monomorphic ventricular tachycardia.

The perils of pharmacological treatment for obesity: a case of sibutramine-associated cardiomyopathy and malignant arrhythmias.

A 58-year-old woman presented with severe left ventricular dysfunction and malignant arrhythmias after taking combination drug treatment for weight loss. The combination treatment included sibutramine, liothyronine, hydrochlorothiazide diuretic, metformin and fucus. The effect of these drugs individually and in combination is discussed, with particular reference to it being a malignant combination. The patient showed reversability of the left ventricular dysfunction and negative ventricular stimulation studies after cessation of the drug concoction.

Direct effects of arsenic trioxide on action potentials in isolated cardiac tissues: importance of the choice of species, type of cardiac tissue and perfusion time.

INTRODUCTION: The aim of the present study was to evaluate direct/acute effects of arsenic trioxide on action potentials (APs) in isolated cardiac tissues, and to investigate if the choice of species and tissue and the duration of the perfusion play a role in arsenic-induced acute/direct prolongation of AP/QT. METHODS AND RESULTS: Direct electrophysiological effects of arsenic trioxide were measured in cardiac tissues isolated from four different species using micro-electrode recording. Arsenic (after 30 to 95 min perfusion at 10 µM) significantly prolonged APD(90), increased triangulation of the AP and elicited early afterdepolarizations (EADs) only in isolated guinea-pig and dog Purkinje fibers but not in rabbit and porcine (minipig) Purkinje fibers. Arsenic induced a prolongation of the APD(90) and increases in triangulation and the occurrence of EADs was not observed in papillary muscles of guinea-pigs and rabbits. Arsenic at 4 increasing concentrations from 0.1 µM to 10 µM at the standard perfusion-time of 15 min per concentration, and after a continuous 90-min perfusion at 1 µM and 1 Hz did not induce these direct effects on APD(90), triangulation and EADs in isolated guinea-pig Purkinje fibers, but it at 1 µM elicited EADs in 2 out of 7 preparations after 90 min at 0.2 Hz. DISCUSSION: The present study demonstrates that the choice of species and cardiac tissue as well as perfusion-time play important roles in arsenic-induced direct/acute effects on APD(90) and induction of EADs in vitro.

Particulate air pollution induces arrhythmia via oxidative stress and calcium calmodulin kinase II activation.

Ambient particulate matter (PM) can increase the incidence of arrhythmia. However, the arrhythmogenic mechanism of PM is poorly understood. This study investigated the arrhythmogenic mechanism of PM. In Sprague-Dawley rats, QT interval was increased from 115.0±14.0 to 142.1±18.4ms (p=0.02) after endotracheal exposure of DEP (200µg/ml for 30min, n=5). Ventricular premature contractions were more frequently observed after DEP exposure (100%) than baseline (20%, p=0.04). These effects were prevented by pretreatment of N-acetylcysteine (NAC, 5mmol/L, n=3). In 12 Langendorff-perfused rat hearts, DEP infusion of 12.5µg/ml for 20min prolonged action potential duration (APD) at only left ventricular base increasing apicobasal repolarization gradients. Spontaneous early afterdepolarization (EAD) and ventricular tachycardia (VT) were observed in 8 (67%) and 6 (50%) hearts, respectively, versus no spontaneous triggered activity or VT in any hearts before DEP infusion. DEP-induced APD prolongation, EAD and VT were successfully prevented with NAC (5mmol/L, n=5), nifedipine (10µmol/L, n=5), and active Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) blockade, KN 93 (1µmol/L, n=5), but not by thapsigargin (200nmol/L) plus ryanodine (10µmol/L, n=5) and inactive CaMKII blockade, KN 92 (1µmol/L, n=5). In neonatal rat cardiomyocytes, DEP provoked ROS generation in dose dependant manner. DEP (12.5µg/ml) induced apoptosis, and this effect was prevented by NAC and KN 93. Thus, this study shows that in vivo and vitro exposure of PM induced APD prolongation, EAD and ventricular arrhythmia. These effects might be caused by oxidative stress and CaMKII activation.

Sustained monomorphic ventricular tachycardia after adenosine infusion.

Adenosine is used as pharmacological treatment of the first choice for the termination of regular small complex tachycardia. Although it is considered safe in this context, several reports of short lasting proarrythmic effects have been described. We present a case of a sustained monomorphic ventricular tachycardia following adenosine infusion.

Amifostine protection against doxorubicin cardiotoxicity in rats.

Aminothiol amifostine (AMI) protects against toxic effects of both ionizing radiation and numerous anticancer drugs. The aim of this study was to investigate the potential protective effects of AMI against doxorubicin (DOX)-induced cardiotoxicity in rats. Male Wistar rats were treated with AMI (75 mg/kg i.p.) and/or DOX (1.25 mg/kg i.p.), 4 times per week, for 4 weeks. Mortality, general condition and body weight of the animals were observed during the whole treatment, and for a further 4 weeks, until the end of experiment. Evaluation of cardioprotective efficacy of AMI was performed by analyzing the electrocardiographic parameters and response to the pro-arrhythmic agent aconitine, as well as activity registration of the in situ rat heart preparations. Necropsy was also performed at the end of the experiment, and heart excision, weight and macroscopic examination were done before histological evaluation. Doxorubicin caused rat heart disturbances manifested by prominent electrocardiographic changes (Salpha-T prolongation and T-wave flattening), significantly enhanced response to aconitine, decrease of the heart rate and contractility, as well as histopathologically verified myocardial lesions. The heart changes were accompanied by 40% mortality rate, significant decline in body mass and severe effusion intensity score in 66.6% of the animals. Application of AMI before each dose of DOX significantly reduced or completely prevented its toxic effects. Therefore, since AMI had very good protective effects against a high dose of DOX given as a multiple, low, unitary dose regimen, not only on the heart but on the whole rat as well, it could be recommended for further investigation in this potentially new indication for clinical application.

Adenosine induced ventricular arrhythmias in the emergency room.

While adenosine effectively terminates most supraventricular tachycardias (SVT), rare case reports have demonstrated its proarrhythmic potential, including induction of ventricular tachycardia (VT). The aim of this study was to define the proarrhythmic effects of adenosine in a large, unselected population. During a 5-year period, adenosine was used (average dose 9.7 mg) in the emergency room to manage 187 episodes of tachycardia in 127 patients. In two thirds of the cases, adenosine induced ventricular ectopy following successful termination of SVT, including premature ventricular complexes (PVC) and nonsustained VT. The adenosine induced PVCs and VT were transient and self-terminating. More than half had a right bundle branch block morphology with a superior axis that suggested an origin in the inferior left ventricular septum. In conclusion, although adenosine is commonly used in clinical practice to treat SVTs, we found that it induced PVCs and VT in two thirds of the patients. The high incidence of ventricular arrhythmias following adenosine infusion was surprising but did not require further intervention. These arrhythmias appeared to frequently originate from the inferior left ventricular septum, suggesting that this area may be particularly susceptible to the proarrhythmic effects of adenosine.

Supraventricular arrhythmia: a complication of 5-fluorouracil therapy.

5-Fluorouracil is an S-phase-specific, synthetic pyrimidine antimetabolite, which is used as a cytostatic agent for a variety of malignant lesions, either singly or in multidrug regimens. Gastrointestinal toxicity and myelosuppression are the most common adverse reactions, but, of late, clinical cardiotoxicity has been reported in both prospective and retrospective studies. We present our experience of clinical cardiotoxicity in five patients.

Fatal cardiac ischaemia associated with prolonged desflurane anaesthesia and administration of exogenous catecholamines.

PURPOSE: Four cardiac ischaemic events are reported during and after prolonged anaesthesia with desflurane. CLINICAL FEATURES: We have evaluated desflurane in 21 consecutive patients undergoing advanced head and neck reconstructive surgery. Four deaths occurred which were associated with cardiac ischaemic syndromes either during or immediately after operation. All patients in the study received a similar anaesthetic. This comprised induction with propofol and maintenance with alfentanil and desflurane in oxygen-enriched air. Inotropic support (either dopamine or dobutamine in low dose, 5 micrograms.kg.min-1) was provided as part of the anaesthetic technique in all patients. Critical cardiovascular incidents were observed in each of the four patients during surgery. These were either sudden bradycardia or tachycardia associated with ST-segment electrocardiographic changes. The four patients who died had a documented past history of coronary heart disease and were classified American Society of Anesthesiologists (ASA) II or III. One patient (#2) did not survive anaesthesia and surgery and the three others died on the first, second and twelfth postoperative days. Enzyme increases (CK/CK-MB) were available in three patients and confirmed myocardial ischaemia. CONCLUSION: These cases represent an unexpected increase in the immediate postoperative mortality for these types of patients and this anaesthetic sequence.

Methotrexate-linked ventricular arrhythmias.

A 36-year-old male, who 1 year previously had survived a large anterior myocardial infarction, followed by cardiac arrest, was treated a few months for psoriasis with oral methotrexate, at single weekly oral doses of up to 10 mg, when he had to be hospitalized due to anginal pain and palpitation. Repeated 24-hour electrocardiogram recordings revealed ventricular ectopy up to 580 premature beats per hour. The ventricular premature beats were almost completely abolished after a few days' discontinuation of methotrexate therapy but recurred a few hours after an attempt to restart it had been made. A coronary angiogram showed only minimal wall abnormalities. Electrophysiological testing and endomyocardial biopsy were normal.