BACKGROUND: The Htr3a antagonist, ondansetron, has been reported to prolong the QT interval and induce Torsades de pointes in the treatment of postoperative nausea and vomiting. To explore the mechanisms underlying these findings, we examined the effects of ondansetron on the mouse cardiac voltage-gated K⁺ (Kv) channel. METHODS AND RESULTS: Ondansetron increased QT intervals in late pregnant (LP) mice. We measured the Kv channels in freshly isolated left ventricular (LV) myocytes from non-pregnant (NP) and late pregnant (LP) mice, using patch-clamp electrophysiology. Ondansetron blocked Kv current at a dose of 50 µM, and reduced the amplitude of peak current densities in a dose-dependent manner (0, 1, 5, 50 µM), in LP but not in NP mice. In contrast, serotonin and the Htr3 agonist, m-CPBG, increased Kv current densities in NP, but not in LP mice. Interestingly, during pregnancy, serum serotonin levels were markedly increased, suggesting the saturation of the effect of serotonin. Immunostaning data showed that Kv4.3 protein and Htr3a co-localize at the membrane and t-tubule of cardiomyocytes. Moreover, Kv4.3 membrane trafficking was enhanced in response to Htr3a-mediated serotonin stimulation in NP, but not in LP mice. Membrane analysis showed that serotonin enhances Kv4.3 membrane trafficking in NP, but not LP mice. CONCLUSION: Ondansetron reduced Kv current densities, and reduced the Kv4.3 membrane trafficking in LP mouse ventricular cardiomyocytes. This data suggests that QT prolongation by ondansetron is mediated by the reduction of Kv current densities and Kv4.3 membrane trafficking.
Animals ; Electrophysiology ; Membranes ; Mice* ; Muscle Cells* ; Myocytes, Cardiac ; Ondansetron* ; Postoperative Nausea and Vomiting ; Pregnancy ; Serotonin ; Torsades de Pointes

A 77-year-old woman presented with exertional dyspnea six days after left pectoral pacemaker implantation. Chest radiography at presentation showed that her left diaphragm was elevated when compared to earlier films. A fluoroscopic sniff test confirmed left diaphragmatic paralysis. Thoracic computed tomography did not reveal any major vascular or lung parenchymal injury; however, phrenic nerve injury on direct needle puncture during the original surgery was suspected. The patient's small body size may have increased the risk of this injury. Delayed-onset unilateral diaphragmatic paralysis appears to be a rare complication of cardiac device implantation.
Aged ; Body Size ; Diaphragm ; Dyspnea ; Female ; Humans ; Lung ; Needles ; Phrenic Nerve ; Punctures ; Radiography ; Respiratory Paralysis* ; Thorax

A 55-year-old woman was admitted because of sudden onset of chest tightness after ingesting a herbal medicine. She experienced refractory ventricular arrhythmia after admission. Electrocardiography showed ST-segment abnormalities that mimicked acute myocardial infarction, but the coronary artery was found to be normal. After conservative management, the cardiac rhythm was stabilized. This was an unusual case of aconitine intoxication that mimicked acute myocardial infarction.
Aconitine* ; Arrhythmias, Cardiac ; Coronary Vessels ; Electrocardiography ; Female ; Herbal Medicine ; Humans ; Middle Aged ; Myocardial Infarction* ; Tachycardia, Ventricular ; Thorax

Flecainide acetate is a potent class IC anti-arrhythmic drug with a major sodium channel blocking effect. Flecainide toxicity can cause myocardial impairment and precipitate circulatory collapse. It may also result in life-threatening arrhythmia, although cases of flecainide-induced torsades de pointes are rare. Furthermore, the electrical and hemodynamic deteriorations observed during flecainide toxicity may not respond to conventional treatments. In the present study, we report the case of a 20-year-old Korean man with flecainide poisoning, who presented with hypotension. The patient was successfully treated with sodium bicarbonate, amiodarone, MgSO₄, and lidocaine, with no recourse to extracorporeal therapy. Although there is no standard therapy for flecainide toxicity, this report demonstrates that intensive pharmacological treatment is beneficial in cases of flecainide overdose.
Amiodarone ; Arrhythmias, Cardiac ; Drug-Related Side Effects and Adverse Reactions ; Flecainide ; Hemodynamics ; Humans ; Hypotension ; Lidocaine ; Poisoning ; Shock ; Sodium Bicarbonate ; Sodium Channels ; Torsades de Pointes* ; Young Adult

Reynolds D, Duray GZ, Omar R, Soejima K, Neuzil P, Zhang S, Narasimhan C, Steinwender C, Brugada J, Lloyd M, Roberts PR, Sagi V, Hummel J, Bongiorni MG, Knops RE, Ellis CR, Gornick CC, Bernabei MA, Laager V, Stromberg K, Williams ER, Hudnall JH, Ritter P; Micra Transcatheter Pacing Study Group.

Dizziness is a common symptom in patients with diabetes mellitus; it can lead to or may be confused with presyncope or syncope. The causes of these three symptoms include various drugs, metabolic decompensation, cerebrovascular diseases, vestibular diseases, and diabetic autonomic neuropathy. Although cardiac autonomic neuropathy (CAN) in patients with diabetes is associated with increased cardiovascular morbidity and mortality, CAN might exist in a subclinical state before patients develop resting tachycardia, exercise intolerance, postural hypotension, cardiac dysfunction, and diabetic cardiomyopathy. Thus, it is important to detect CAN in the early phase. This article aimed to review the pathogenesis, manifestations, diagnosis, and treatment of diabetic CAN related to dizziness, presyncope, and syncope.
Cerebrovascular Disorders ; Diabetes Mellitus ; Diabetic Cardiomyopathies ; Diabetic Neuropathies* ; Diagnosis ; Dizziness* ; Humans ; Hypotension, Orthostatic ; Mortality ; Syncope* ; Tachycardia ; Vestibular Diseases

Since inappropriate sinus tachycardia (IST) occurs due to various reasons, it can be diagnosed after exclusion of all causes and diseases that may result in sinus tachycardia. In particular, it is important to differentiate postural orthostatic tachycardia syndrome (POTS), and a multidisciplinary approach is necessary for differentiating psychiatric events. In addition, whether the clinical symptoms coincide with tachycardia events should be checked before treatment. β-adrenergic blocker is the most effective drug, and exercise training is recommended for controlling clinical symptoms. Furthermore, discontinuation of smoking and alcohol consumption, and decrease in caffeine intake may be useful. Recently, ivabradine has been found effective, and catheter ablation can be considered in cases of drug refractory IST presenting with clinical symptoms.
Alcohol Drinking ; Arrhythmias, Cardiac ; Caffeine ; Catheter Ablation ; Postural Orthostatic Tachycardia Syndrome ; Smoke ; Smoking ; Tachycardia ; Tachycardia, Sinus*

Orthostatic intolerance is the inability to tolerate an upright posture as a consequence of varying degrees of autonomic nervous system dysfunction. Orthostatic intolerance syndromes can be classified into at least 3 categories: 1) orthostatic hypotension, 2) neurally mediated (reflex) syncope, and 3) postural orthostatic tachycardia syndrome. In this review, we discuss the pathophysiology and etiologies of orthostatic hypotension and postural orthostatic tachycardia syndrome, and propose their diagnostic and therapeutic alternatives.
Autonomic Nervous System ; Hypotension, Orthostatic ; Orthostatic Intolerance* ; Postural Orthostatic Tachycardia Syndrome ; Posture ; Syncope

BACKGROUND AND OBJECTIVES: Numerous clinical studies have demonstrated chronic right ventricular (RV) pacing induced left ventricular (LV) dyssynchrony and LV systolic dysfunction in patients with permanent pacemaker. However, only a limited number of studies have focused on RV dysfunction. We sought to determine the prevalence and identify the clinical predictors of RV dysfunction in patients with chronic RV pacing. SUBJECTS AND METHODS: We enrolled 72 patients (mean age 72.7±11.1 years, men 36.1%) who underwent permanent pacemaker implantation without RV dysfunction in baseline examination. Baseline clinical characteristics, laboratory data, echocardiographic parameters and pacing profiles were assessed. Follow up 2-dimentional echocardiography was used to identify the presence of RV dysfunction. RESULTS: We divided patients based on the criteria of either presence or absence of RV dysfunction, where RV dysfunction is defined as decreased tricuspid annulus systolic velocity (<11 cm/sec) in tissue Doppler image. Sixteen patients (22.2%) in our study showed meaningful RV dysfunction. Patients with RV dysfunction had lower LV ejection fraction (57.5±10.8% versus 64.6±9.1%, p<0.05) and higher B-type natriuretic peptide (BNP) levels (700.3±152.9 pg/mL versus 329.4±332.4 pg/mL, p<0.05) compared to patients without RV dysfunction. Implantation of VVI type pacemaker was associated with presence of RV dysfunction (81.3% versus 33.3%, p<0.05). Higher cumulative ratio of total RV pacing was associated with increased tendency for RV dysfunction. No statistically significant correlation was observed between the groups (70.7±13.2% in RV dysfunction group, 61.7±38.3% in non-RV dysfunction group, p=0.094). CONCLUSION: In this study, meaningful proportion of patients showed chronic RV pacing induced RV dysfunction. RV dysfunction was associated with lower LV systolic function, higher BNP level and VVI type pacemaker.
Echocardiography ; Follow-Up Studies ; Humans ; Male ; Natriuretic Peptide, Brain ; Prevalence* ; Ventricular Dysfunction, Right*

A 43-year-old man who had received mitral and aortic valve replacement surgery underwent the implantation of an implantable cardioverter defibrillator (ICD) for sustained ventricular tachycardia. The patient presented with a sudden jolting sensation in his left upper chest area one year after the device implantation. He had a history of vigorous upper body exercise during the several months of the follow-up period. Device interrogation revealed complete sensing and capture failure. The ventricular lead impedance was in the normal range, but the high voltage impedance had dropped to less than 10 Ω. Four inappropriate shocks for ventricular fibrillation had been delivered due to over-sensing of the atrial signal on the ventricular lead. Chest radiography showed ventricular lead displacement with extreme rotation and flipping-over of the generator. In the lead revision operation, the old ventricular lead was extracted and replaced, and the generator was fixed more deeply in the pocket with a non-absorbable ligature.
Adult ; Aortic Valve ; Defibrillators ; Defibrillators, Implantable* ; Electric Impedance ; Follow-Up Studies ; Humans ; Ligation ; Radiography ; Reference Values ; Sensation ; Shock* ; Tachycardia, Ventricular ; Thorax ; Ventricular Fibrillation