Bundle of His ; Bundle-Branch Block ; Cardiac Pacing, Artificial ; Electrocardiography ; Humans ; Purkinje Fibers

We reviewed the anatomical characteristics of the conduction system in the ventricles of human and ungulate hearts and then raised some questions to be answered by clinical and anatomical studies in the future. The ventricular conduction system is a 3-dimensional structure as compared to the 2-dimensional character of the atrial conduction system. The proximal part consisting of the atrioventricular node, the bundle of His and fascicles are groups of conducting cells surrounded by fibrous connective tissue so as to insulate from the underlying myocardium. Their location and morphological characters are well established. The bundle of His is a cord like structure but the left and right fascicles are broad at the proximal and branching at the distal part. The more distal part of fascicles and Purkinje system are linear networks of conducting cells at the immediate subendocardium but the intra-mural network is detected at the inner half of the ventricular wall. The papillary muscle also harbors Purkinje system not in the deeper part. It is hard to recognize histologically in human hearts but conducting cells as well as Purkinje cells are easily recognized in ungulate hearts. Further observation on human and ungulate hearts with myocardial infarct, we could find preserved Purkinje system at the subendocardium in contrast to the damaged system at the deeper myocardium. Further studies are necessary on the anatomical characteristics of this peripheral conduction system so as to correlate the clinical data on hearts with ventricular arrhythmias.
Arrhythmias, Cardiac ; Atrioventricular Node ; Bundle of His ; Connective Tissue ; Heart ; Heart Conduction System ; Humans ; Myocardial Infarction ; Myocardium ; Papillary Muscles ; Purkinje Cells ; Purkinje Fibers ; Tachycardia, Ventricular

Dihydropyridine (DHP) calcium channel blockers (CCBs) have been widely used to treat of several cardiovascular diseases. An excessive shortening of action potential duration (APD) due to the reduction of Ca2+ channel current (I(Ca)) might increase the risk of arrhythmia. In this study we investigated the electrophysiological effects of nicardipine (NIC), isradipine (ISR), and amlodipine (AML) on the cardiac APD in rabbit Purkinje fibers, voltage-gated K+ channel currents (I(Kr), I(Ks)) and voltage-gated Na+ channel current (I(Na)). The concentration-dependent inhibition of Ca2+ channel currents (I(Ca)) was examined in rat cardiomyocytes; these CCBs have similar potency on I(Ca) channel blocking with IC50 (the half-maximum inhibiting concentration) values of 0.142, 0.229, and 0.227 nM on NIC, ISR, and AML, respectively. However, ISR shortened both APD50 and APD90 already at 1 microM whereas NIC and AML shortened APD50 but not APD90 up to 30 microM. According to ion channel studies, NIC and AML concentration-dependently inhibited I(Kr) and I(Ks) while ISR had only partial inhibitory effects (<50% at 30 microM). Inhibition of I(Na) was similarly observed in the three CCBs. Since the I(Kr) and I(Ks) mainly contribute to cardiac repolarization, their inhibition by NIC and AML could compensate for the AP shortening effects due to the block of I(Ca).
Action Potentials ; Amlodipine ; Animals ; Antihypertensive Agents ; Arrhythmias, Cardiac ; Calcium Channel Blockers* ; Calcium Channels* ; Calcium* ; Cardiovascular Diseases ; Inhibitory Concentration 50 ; Ion Channels ; Isradipine ; Myocytes, Cardiac ; Nicardipine ; Purkinje Fibers ; Rats

Sibutramine is an anorectic that has been banned since 2010 due to cardiovascular safety issues. However, counterfeit drugs or slimming products that include sibutramine are still available in the market. It has been reported that illegal sibutramine-contained pharmaceutical products induce cardiovascular crisis. However, the mechanism underlying sibutramine-induced cardiovascular adverse effect has not been fully evaluated yet. In this study, we performed cardiovascular safety pharmacology studies of sibutramine systemically using by hERG channel inhibition, action potential duration, and telemetry assays. Sibutramine inhibited hERG channel current of HEK293 cells with an IC50 of 3.92 muM in patch clamp assay and increased the heart rate and blood pressure (76 Deltabpm in heart rate and 51 DeltammHg in blood pressure) in beagle dogs at a dose of 30 mg/kg (per oral), while it shortened action potential duration (at 10 muM and 30 muM, resulted in 15% and 29% decreases in APD50, and 9% and 17% decreases in APD90, respectively) in the Purkinje fibers of rabbits and had no effects on the QTc interval in beagle dogs. These results suggest that sibutramine has a considerable adverse effect on the cardiovascular system and may contribute to accurate drug safety regulation.
Action Potentials ; Animals ; Blood Pressure ; Cardiovascular System ; Counterfeit Drugs ; Dogs ; Heart Rate ; HEK293 Cells ; Inhibitory Concentration 50 ; Pharmaceutical Preparations ; Pharmacology* ; Purkinje Fibers ; Rabbits ; Telemetry

A contralateral bundle branch block (BBB) aberration during tachycardia with a preexisting BBB strongly suggests the presence of ventricular tachycardia. We report on a middle-aged, female patient presented with wide QRS tachycardia. The patient had orthodromic atrioventricular tachycardia with a left BBB aberration in the presence of a preexisting right BBB due to an abnormal His-Purkinje system. We learned that the contralateral BBB aberration with supraventricular tachycardia could be seen when the His-Purkinje system was abnormal.
Bundle of His ; Bundle-Branch Block* ; Female ; Humans ; Purkinje Fibers ; Tachycardia ; Tachycardia, Supraventricular* ; Tachycardia, Ventricular

Sulfites are used as anti-microbial and anti-oxidant agents in the food and pharmaceutical industries. Curcumin, a flavonoid, is an Asian spice that shows neuroprotective activities. The current study aimed to stereologically assess the rats' cerebellar cortex and rotarod performance following sulfite exposure and determine the possible neuroprotective potential of curcumin. The rats were divided into five groups: distilled water, olive oil, curcumin (100 mg/kg/day), sodium metabisulfite (25 mg/kg/day), and sodium metabisulfite+curcumin. At 56 days after treatment, rotarod performance was tested, and then the cerebellum was removed for stereological analysis. The study results revealed 31%, 36%, 19% and 24% decrease in the total volume of the cerebellum, cortex, the total number of the Purkinje cells and length of the nerve fibers in the cortex per Purkinje, respectively in the sodium metabisulfite-treated rats compared to the distilled water group (p<0.01). The pre-trained animals on the rotarod apparatus were tested first on the fixed speed rotarod protocol followed by the accelerating rotarod protocol two days later. The results showed a significant decrease in the latency to fall in both test in sulfite-treated rats. The sulfite effects on the structural parameters and rotarod performance were significantly protected by the concomitant curcumin treatment (p<0.001). Sulfite can induce structural and functional changes in the rats' cerebellum and concomitant curcumin prescription plays a neuroprotective role.
Animals ; Asian Continental Ancestry Group ; Cerebellar Cortex ; Cerebellum ; Curcumin* ; Drug Industry ; Humans ; Nerve Fibers ; Olea ; Prescriptions ; Purkinje Cells ; Rats* ; Sodium* ; Spices ; Sulfites ; Water ; Olive Oil

PURPOSE: We hypothesized that Purkinje potential and their preferential conduction to the left ventricle (LV) posteroseptum during sinus rhythm (SR) are part of reentrant circuits of idiopathic left ventricular tachycardia (ILVT) and reentry anchors to papillary muscle. MATERIALS AND METHODS: In 14 patients with ILVT (11 men, mean age 31.5+/-11.1 years), we compared Purkinje potential and preferential conduction during SR with VT by non-contact mapping (NCM). If clear Purkinje potential(SR) was observed in the LV posteroseptum and the earliest activation site (EA) of preferential conduction at SR (EASR) was well matched with that of VT (EAVT), EASR was targeted for radiofrequency catheter ablation (RFCA). Also, the anatomical locations of successful ablation sites were evaluated by echocardiography in five additional patients. RESULTS: 1) All induced VTs exhibited clear Purkinje potential(VT) and preferential conduction in the LV posteroseptum. The Purkinje potential(VT) and EAVT was within 5.8+/-8.2 mm of EASR. However, the breakout sites of VT were separated by 30.2+/-12.6 mm from EAVT to the apical side. 2) Purkinje potential(SR) demonstrated a reversed polarity to Purkinje potential(VT), and the interval of Purkinje potential(SR)-QRS was longer than the interval of Purkinje potential(VT)-QRS (p<0.02) 3) RFCA targeting EASR eliminated VT in all patients without recurrence within 23.3+/-7.5 months, and the successful ablation site was discovered at the base of papillary muscle in the five additional (100%) patients. CONCLUSION: NCM-guided localization of EASR with Purkinje potential(SR) matches well with EAVT with Purkinje potential(VT) and provides an effective target for RFCA, potentially at the base of papillary muscle in patients with ILVT.
Adult ; Catheter Ablation ; Electrophysiology ; Female ; Humans ; Male ; Purkinje Fibers/*physiology ; Tachycardia, Ventricular/*physiopathology/surgery ; Ventricular Dysfunction, Left/*physiopathology/surgery ; Young Adult

Arrhythmias, Cardiac ; pathology ; physiopathology ; Humans ; Purkinje Fibers

KIOM-79, a mixture of ethanol extracts from four herbs (parched Puerariae radix, gingered Magnoliae cortex, Glycyrrhizae radix and Euphorbiae radix), has been developed for the potential therapeutic application to diabetic symptoms. Because screening of unexpected cardiac arrhythmia is compulsory for the new drug development, we investigated the effects of KIOM-79 on the action potential (AP) and various ion channel currents in cardiac myocytes. KIOM-79 decreased the upstroke velocity (Vmax) and plateau potential while slightly increased the duration of action potential (APD). Consistent with the decreased Vmax and plateau potential, the peak amplitude of Na+ current (INa) and Ca2+ current (ICa,L) were decreased by KIOM-79. KIOM-79 showed dual effects on hERG K+ current; increase of depolarization phase current (Idepol) and decreased tail current at repolarization phase (Itail). The increase of APD was suspected due to the decreased Itail. In computer simulation, the change of cardiac action potential could be well simulated based on the effects of KIOM-79 on various membrane currents. As a whole, the influence of KIOM-79 on cardiac ion channels are minor at concentrations effective for the diabetic models (0.1-10 microg/mL). The results suggest safety in terms of the risk of cardiac arrhythmia. Also, our study demonstrates the usefulness of the cardiac computer simulation in screening drug-induced long-QT syndrome.
Action Potentials/*drug effects ; Animals ; Cell Line ; Computer Simulation ; Female ; Ginger/chemistry ; Humans ; Ion Channels/*physiology ; Long QT Syndrome/diagnosis ; Male ; Membrane Potentials/drug effects/physiology ; Myocytes, Cardiac/*drug effects/physiology ; Patch-Clamp Techniques ; Plant Extracts/*pharmacology ; Pueraria/chemistry ; Purkinje Fibers/drug effects/physiology ; Rabbits ; Rats ; Rats, Sprague-Dawley

KIOM-79, a mixture of ethanol extracts from four herbs (parched Puerariae radix, gingered Magnoliae cortex, Glycyrrhizae radix and Euphorbiae radix), has been developed for the potential therapeutic application to diabetic symptoms. Because screening of unexpected cardiac arrhythmia is compulsory for the new drug development, we investigated the effects of KIOM-79 on the action potential (AP) and various ion channel currents in cardiac myocytes. KIOM-79 decreased the upstroke velocity (Vmax) and plateau potential while slightly increased the duration of action potential (APD). Consistent with the decreased Vmax and plateau potential, the peak amplitude of Na+ current (INa) and Ca2+ current (ICa,L) were decreased by KIOM-79. KIOM-79 showed dual effects on hERG K+ current; increase of depolarization phase current (Idepol) and decreased tail current at repolarization phase (Itail). The increase of APD was suspected due to the decreased Itail. In computer simulation, the change of cardiac action potential could be well simulated based on the effects of KIOM-79 on various membrane currents. As a whole, the influence of KIOM-79 on cardiac ion channels are minor at concentrations effective for the diabetic models (0.1-10 microg/mL). The results suggest safety in terms of the risk of cardiac arrhythmia. Also, our study demonstrates the usefulness of the cardiac computer simulation in screening drug-induced long-QT syndrome.
Action Potentials/*drug effects ; Animals ; Cell Line ; Computer Simulation ; Female ; Ginger/chemistry ; Humans ; Ion Channels/*physiology ; Long QT Syndrome/diagnosis ; Male ; Membrane Potentials/drug effects/physiology ; Myocytes, Cardiac/*drug effects/physiology ; Patch-Clamp Techniques ; Plant Extracts/*pharmacology ; Pueraria/chemistry ; Purkinje Fibers/drug effects/physiology ; Rabbits ; Rats ; Rats, Sprague-Dawley