Effect of iron overload on electrophysiology of slow reaction autorhythmic cells of left ventricular outflow tract in guinea pigs

Objective: To investigate the electrophysiology effects and mechanism of iron overload on the slow response autorhythmic cells in the left ventricular outflow tract of guinea pigs.Methods: Standard microelectrode cell recording techniques were adopted to observe the electrophysiological effects of different concentrations of Fe^(2+)(100 μmol/L, 200 μmol/L) on the left ventricular outflow tract autorhythmic cells.Heart tissues were perfused with FeSO_4(200 μmol/L) combing with CaCl_2(4.2 mmol/L), Verapamil,(1 μmol/L), and nickel chloride(200μmol/L) respectively to observe the influences of these contents on electrophysiology of FeSO_4(200μmol/L) on the left ventricular outflow tract autorhythmic cells.Results: Fe^(2+)at both 100 μmol/L and 200 μmol/L could change the electrophysiological parameters of the slow response autorhythmic cells of the left ventricular outflow tract in a concentrationdependent manner resulting into decrease in Vmax, APA and MDP, slower RPF and VDD, and prolonged APD_(50) and APD_(90)(P all <0.05).Besides, perfusion of increased Ca^(2+) concentration could partially offset the electrophysiological effects of Fe^(2+)(200 μmol/L).The L-type calcium channel(LTCC) blocker Verapamil(1 μmol/L) could block the electrophysiological effects of Fe^(2+)(200 μmol/L).But the T-type calcium channel(TTCC) blocker nickel chloride(NiCl_2, 200 μmol/L) could not block the electrophysiological effects of Fe^(2+)(200 μmol/L).Conclusions: Fe^(2+) can directly change the electrophysiological characteristics of the slow response autorhythmic cells of the left ventricular outflow tract probably through the L-type calcium channel.

Electrophysiology and genetic testing in the precision medicine of congenital deafness:A review

Background:Congenital hearing loss is remarkably heterogeneous,with over 130 deafness genes and thousands of variants,making for innumerable genotype/phenotype combinations.Understanding both the pathophysiology of hearing loss and molecular site of lesion along the auditory pathway permits for significantly individualized counseling.Electrophysiologic techniques such as electrocochleography(ECochG)and electrically-evoked compound action potentials(eCAP)are being studied to localize pathology and estimate residual cochlear vs.neural health.This review describes the expanding roles of genetic and electrophysiologic evaluation in the precision medicine of congenital hearing loss.The basics of genetic mutations in hearing loss and electrophysiologic testing(ECochG and eCAP)are reviewed,and how they complement each other in the diagnostics and prognostication of hearing outcomes.Used together,these measures improve the understanding of insults to the auditory system,allowing for individualized counseling for CI candidacy/outcomes or other habilitation strategies.Conclusion:Despite tremendous discovery in deafness genes,the effects of individual genes on neural function remain poorly understood.Bridging the understanding between molecular genotype and neural and functional phenotype is paramount to interpreting genetic results in clinical practice.The future hearing healthcare provider must consolidate an ever-increasing amount of genetic and phenotypic information in the precision medicine of hearing loss.

Arrhythmic risk stratification in ischemic,non-ischemic and hypertrophic cardiomyopathy:A two-step multifactorial,electrophysiology study inclusive approach

Annual arrhythmic sudden cardiac death ranges from 0.6%to 4%in ischemic cardiomyopathy(ICM),1%to 2%in non-ischemic cardiomyopathy(NICM),and 1%in hypertrophic cardiomyopathy(HCM).Towards a more effective arrhythmic risk stratification(ARS)we hereby present a two-step ARS with the usage of seven non-invasive risk factors:Late potentials presence(≥2/3 positive criteria),premature ventricular contractions(≥30/h),non-sustained ventricular tachycardia(≥1episode/24 h),abnormal heart rate turbulence(onset≥0%and slope≤2.5 ms)and reduced deceleration capacity(≤4.5 ms),abnormal T wave alternans(≥65μV),decreased heart rate variability(SDNN<70ms),and prolonged QT_(c)interval(>440 ms in males and>450 ms in females)which reflect the arrhythmogenic mechanisms for the selection of the intermediate arrhythmic risk patients in the first step.In the second step,these intermediate-risk patients undergo a programmed ventricular stimulation(PVS)for the detection of inducible,truly high-risk ICM and NICM patients,who will benefit from an implantable cardioverter defibrillator.For HCM patients,we also suggest the incorporation of the PVS either for the low HCM Risk-score patients or for the patients with one traditional risk factor in order to improve the inadequate sensitivity of the former and the low specificity of the latter.

In-Cell Nanoelectronics:Opening the Door to Intracellular Electrophysiology

Establishing a reliable electrophysiological recording platform is crucial for cardiology and neuroscience research.Noninvasive and label-free planar multitransistors and multielectrode arrays are conducive to perform the large-scale cellular electrical activity recordings,but the signal attenua-tion limits these extracellular devices to record subthreshold activities.In recent decade,in-cell nanoelectronics have been rapidly developed to open the door to intracellular electrophysi-ology.With the unique three-dimensional nanotopography and advanced penetration strategies,high-throughput and high-fidelity action potential like signal recordings is expected to be realized.This review summarizes in-cell nanoelectronics from versatile nano-biointerfaces,penetration strategies,active/pas-sive nanodevices,systematically analyses the applications in electrogenic cells and especially evaluates the influence of nanodevices on the high-quality intracellular electrophysiological signals.Further,the opportunities,challenges and broad prospects of in-cell nanoelectronics are prospected,expecting to promote the development of in-cell electrophysiological platforms to meet the demand of theoretical investigation and clinical application.

Anesthetic Technique for Transesophageal Electrophysiology Studies in Pediatric Patients with Wolff-Parkinson-White Syndrome

Objective: Patients with Wolff-Parkinson-White (WPW) Syndrome require risk assessment to determine their potential for sudden cardiac death. Transesophageal electrophysiology studies (TEEPS) are an effective risk stratification tool. The purpose of this study is to describe a minimially invasive, effective anesthetic technique to employ during transesophageal electrophysiology studies. Methods: A retrospective review of anesthetic technique utilized during TEEPS. Inclusion criteria;WPW on ECG;age <18 years;and no history of tachycardia, palpitations, or syncope and patient had TEEPS under monitored anesthesia care (MAC). Midazolam, Fentanyl, and Propofol were used in various combinations. Sevoflurane was used during induction period in all GA cases and discontinued 10 minutes prior to initiation of TEEPS. Results: Inclusion criteria were met by 20 patients with an average age of 11.9 years, average weight of 48.9 kg and average height of 149.2 cm. IV sedation was performed on 15%, MAC on 10% and GA in remainder. Airway management techniques included 13.3% LMA, 20% endotrachael tube (ETT) and 66% mask. IV sedation, the initial anesthetic, was found to be cumbersome and uncomfortable. Next was ETT and LMA but trouble pacing was encountered due to positional change of the esophagus relative to the left atrium during ventilation. Mask induction was then performed in remaining 10 patients with TEEPS probe inserted through a nare while anesthesiologist continued mask ventilation. All mask procedures were successful without complications. Conclusions: Induction of anesthesia to perform TEEPS procedures on pediatric patients with Wolff-Parkinson-White syndrome underwent numerous attempts to make the procedure easy, reliable and reproducible for anesthesia and electrophysiologist. The eventual technique that proved to meet these criteria during a transesopheagel electrophysiology procedure was utilization of mask induction with continuous IV sedation.

Effects of Diazoxide Treatments on Electrophysiologyic Properties in Guinea Pig Papillary Muscles Undergoing Ischemia/Reperfusion

The effects of diazoxide treatments on electrophysiologyic properties in guinea pig papillary muscles undergoing ischemia/reperfusion was studied using intracellular microelectrode technique. Twenty-four guinea pigs were randomly divided into three groups (n=8 in each group). In control group, St.Thomas solution was given. In experimental group, St.Thomas solution with diazoxide (100 mol/L) was given. In pretreatment group, the muscle was treated with diazoxide 20 min before arrested with St.Thomas cardioplegia. The results showed that the APD_50 and APD_90 in experimental and pretreatment groups were significantly shorter after 5 and 10 min reperfusion (P<0.01, P<0.05), but longer after 30 min reperfusion (P<0.01, P<0.05) than in control group. In experimental and pretreatment groups, APA, OS, Vmax recovered more quickly than those in control group. The time to re-systole after reperfusion in control group was longer than that in experimental and pretreatment groups. There was no significant difference in RP among three groups. The time of arrest in pretreatment group was longer than that in experimental and pretreatment group (P<0.05). This study indicates that protective effects of St.Thomas solution with diazoxide is better than that of pretreatment with diazoxide or St.Thomas solution alone.

Electrophysiology as a tool to unravel the origin of pancreatic pain

Intense abdominal pain is the most common symptom in chronic pancreatitis, but the underlying mechanisms are not completely understood and pain management remains a significant clinical challenge.The focus of pain origin in chronic pancreatitis traditionally has been on the pancreatic gland, assuming pain to originate in the pancreas or its surrounding organs. However, research in the last decade points to abnormal central nervous system pain processing.For this reason, electroencephalography has been receiving increasing attention. In contrast to imaging methods such as functional magnetic resonance and positron emission tomography, electroencephalogram has excellent temporal resolution making it possible to investigate central processing of pain on a millisecond time scale. Moreover, continuously advancing methodology made it possible to explore brain sources responsible for generation of evoked potentialsand hence to study brain reorganization due to pain in chronic pancreatitis. The aim of this review is to give an overview of the current methods and findings in electroencephalography as a tool to unravel the origin of pancreatic pain.

Tail nerve electrical stimulation-induced walking training promotes restoration of locomotion and electrophysiology in rats with chronic spinal cord injury

Functional recovery is the final goal in the treatment of spinal cord injury. However, to date, few treatment strategies have demonstrated significant locomotor improvement in animal experiments. By using tail nerve electrical stimulation (TANES) as an open-field locomotor training method combined with glial scar ablation and cell transplantation, we have successfully promoted locomotor recovery in rats with chronic spinal cord contusion injury. The purpose of the present study is to further investigate the mechanism of TANES and its effect on electrophysiology. Spinal cord segment T10 of female, adult Long-Evans rats was contused using the NYU impactor device with 25 mm height setting. After injury, rats were randomly divided into three groups. Group I was used as a control without any treatment, group II and group III were subjected to basic treatment including glial scar ablation and transplantation of olfactory lamina propria 6 weeks after injury, and group III received TANES-induced open-field locomotor training weekly after basic treatment. All animals were allowed to survive 22 weeks, except some rats which were transected. Basso, Beattie, and Bresnahan (BBB) open-field locomotor rating scale, horizontal ladder rung walking test, and electrophysiological tests were used to assess the restoration of functional behavior and conduction. Results showed that TANES significantly improves locomotor recovery and spinal cord conduction, reflex, as well as significantly reduces the occurrence of autophagia. Additionally, after transection, trained rats still maintained higher BBB score than that of control rats. This may be related to the activity-dependent plasticity promoted by TANES-induced locomotor training.

Effects of hydrogen sulfide on guinea pig aortic vestibule autorhythmic cells electrophysiology and its mechanism

Objective:To investigate the electrophysiological effects of hydrogen sulfide (H2S) on left ventricular outflow tract autonomic cells in guinea pigs and its mechanism.Methods:Intracellular microelectrode recording technique was used to observe the electrophysiological effects of different concentrations of hydrogen sulfide on the autonomic cells of left ventricular outflow tract.Results: CSE irreversible inhibitor PPG (200 μmol/L) makes the left ventricular outflow tract of autorhythmic cells Vmax, RPF and VDD accelerate, APA increase (P<0.05);CBS synthase inhibitor AOAA (100μmol/L) acts on the autorhythmic cells of the left ventricular outflow tract without effect. The concentration-dependency of the 50, 100 and 200μmol/L NaHS made RPF and VDD of autorhythmic cell of the left ventricular outflow tract decrease with increasing concentration of NaHS, Vmax and APA decrease (P<0.01). The ATP sensitive potassium channel (KATP) blocker glybenclamide (Gli, 20 μmol/L) partially blocked the electrophysiological effects of NaHS (P<0.05). The L-Ca2+ channel agonist Bay K8644 could partially block the electrophysiological effects of NaHS.Conclusion:The autorhythmic cells of the left ventricular outflow tract had endogenous H2S produced by CSE. H2S had a negative chronotropic effect on autorhythmic cells in the left ventricular outflow tract, and its mechanism was related to the inhibition of L-Ca2+ channels by the open KATP pathway.

The Electrophysiology in Idiopathic Senile Macular Hole

Of 12 patients with idiopathic senile full- thickness macular hole, 3 had bilateral involvement, 9 had monocular macular hole. Flash ERG and pattern VEP were performed in the bilateral eyes of all patients. The abnormal rate of the pattern VEP was 93.3% when we used 15' checkboard stimulus, the changes of the VEP appeared as delayed latencies, reduced amplitudes or malformation of P100. The abnormal rate of the flash ERG was 53.3%, showing primary characteristics of reduced amplitudes of cone response b...

Comparison of the Frequency-dependent Effects of Amiodarone on Ventricular Electrophysiology in Congestive Heart Failure Canine Models and Normal Dogs

Objectives To compare the frequency-dependent effects of amiodarone （Ami） on ventricular electrophysiology in fight ventricular rapid pacing-induced congestive heart failure （CHF） canine models. Methods Thirty-two dogs were randomized into four groups： the control group, the Ami group in which the normal dogs were given Ami orally 300 mg a day for 4 -5 weeks, the CHF group induced by right ventricular rapid pacing （240 pulses, min^- 1 for 4 -5 weeks ）, and the group of CHF dogs fed with Ami orally 300 mg a day for 4 - 5 weeks. The techniques of electrical stimulation and monophasic action potential （MAP） recording were used in the electrophysiology studies. Results The effects of Ami on ventricular MAP duration （MAPD90） and effective refractory period （VERP） were not frequency-dependent in CHF dogs. There was also no frequency-dependent effect on the increase in the ratio of VERP to MAPD90 （ VERP/MAPD90 ）. The prolongation of ventricular conduction time was frequencydependent. Conclusions The frequency-dependent effects of Ami on ventricular electrophysiology in CHF dogs were similar to that in normal dogs.

Computer Simulation Methods of Cardiac Electrophysiology

The Luo Rudy models of mammalian ventricular cell were chosen in studying cardiac electrophysiology. Rush and Larsen’s algorithm and adaptive time step methods were used to solve the ordinary differential equations (ODE’s). The operator splitting (or time splitting) and adaptive time step methods were used to solve the partial differential equations (PDE’s) in cardiac tissue conduction models. The alternating direction implicit (ADI) method was used to integrate the PDE. Using these methods we accomplished the simulation programs of single cardiomyocyte model, one dimensional cable model(1 D) and two dimensional(2 D) tissue model. The methods of initiating spiral waves were studied with these software. The data getting from 2 D simulation can be used for further study on isopotential contour lines, spiral wave tip trajectories, and pseudo ECG. The software for computer simulation have been successfully used in simulation studying of electrophysiology properties of single cardiomyocyte, conduction in one dimensional cable model(1 D) and two dimensional(2 D) tissue model.

Effect of tetrandrine on cellular electrophysiology and calcium uptake of myocardium in guinea pigs and dogs

Objective To study the effects of tetrandrine, a Chinese herbal medicine, on the action potential (AP),contraction as well as sarcoplasmic reticulum (SR) calcium uptake of myocardium in guinea-pigs and dogs.Methods Changes in AP, dV/dt, peak tension (PT) and dT/dt of myocardial cells were studied using the technique of glass electrode. Changes of the calcium uptake rate by sarcoplasmic reticulum and release of inorganic phosphate from sarcoplasmic reticulum were assessed with biochemical techniques.Results Tetrandrine exerts a concentration-dependent and frequency-dependent negative inotropic effect and shortens action potential duration. Tetrandrine depresses both dT(E)/dt and dT(L)/dt as well as the tension of myocardium, and reduces dV/dt and amplitude only in the slow action potential, thus implying that tetrandrine blocks the slow calcium channel. In addition, compared with thapsigargin, a specific inhibitor of Ca2+-ATPase on SR, tetrandrine more apparently suppresses the contraction of the myocardium.Conclusions Tetrandrine is a wide-range calcium antagonist of plant origin. Not only it blocks the voltageoperated calcium channels as other authors reported, but also may play an important role in affecting the function of Ca2+ -ATPase and calcium release channels on SR. From this study, we also suggest that the calcium channel appears to be more critical than SR for the contraction of my ocardium.

Asynchronization in Changes of Electrophysiology and Pathology of Spinal Cord Motor Neurons in Rats Following Middle Cerebral Artery Occlusion

Background： Motor dysfunction is common in stroke patients. Clinical electrophysiological studies suggest that transsynaptic degeneration occurred in the lower motor neurons, while pathological evidence is lacked. This study aimed to combine the electrophysiological and pathological results to prove the existence of transsynaptic degeneration in the motor system after stroke. Methods： Modified neurologic severity score, electrophysiological, and pathological assessments were evaluated in rats before middle cerebral artery occlusion （MCAO）, and at 24 hours, 7 days, and 14 days after MCAO. Paired and independent-sample t-tests were applied to assess the changes of electrophysiological and pathological data. Results： Compound motor action potential amplitude in the paretic side was significantly lower than the nonparetic side at both 24 hours （61.9 ± 10.4 vs. 66.6 ± 8.9, P 〈 0.05） and 7 days （60.9 ± 8.4 vs. 67.3 ±9.6, P 〈 0.05） after MCAO. Motor unit number estimation of the paretic side was significantly less than the nonparetic side （379.0 ± 84.6 vs. 445.0 ±9.5, P 〈 0.05） at 7 days after MCAO. Until 14 days after stroke, the pathological loss of motor neurons was detected. Motor neurons in 14-day MCAO group were significantly decreased, compared with control group （5.3 ± 0.7 vs. 7.3 ± 1.8, P 〈 0.05）. Conclusions： Both electrophysiological and pathological studies showed transsynaptic degeneration after stroke. This study identified the asynchronization in changes of electrophysiology and pathology. The abnormal physiological changes and function impairment can be detected in the early stage and recovered quickly, while the pathological loss of motor neuron can be detected only in a later stage.

Cardiac differentiation and electrophysiology characteristics of bone marrow mesenchymal stem cells

Objective To review the progress of cardiac differentiation and electrophysiological characteristics of bone marrow mesenchymal stem cells. Data sources The databases of PubMed, Springer Link, Science Direct and CNKI were retrieved for papers published from January 2000 to January 2012 with the key words of ＂bone marrow mesenchymal stem cells, cardiac or heart, electrophysiology or electrophysiological characteristics＂. Study selection The articles concerned cardiac differentiation and electrophysiological characteristics of bone marrow mesenchymal stem cells were collected. After excluding papers that study purposes are not coincident with this review or contents duplicated, 56 papers were internalized at last. Results For the treatment of myocardial infarction and myocardiac disease, the therapeutic effects of transplantation of bone marrow mesenchymal stem cells which have the ability to develop into functional myocardial cells by lots of methods have been proved by many researches. But the arrhythmogenic effect on ventricles after transplantation of bone marrow mesenchymal stem cells derived myocardial cells is still controversial in animal models. Certainly, the low differentiation efficiency and heterogeneous development of electricial function could be the most important risk for proarrhythmia. Conclusion Many studies of cardiac differentiation of bone marrow mesenchymal stem cells have paid attention to improve the cardiac differentiation rate, and the electrophysiology characteristics of the differentiated cells should be concerned for the risk for proarrhythmia as well.

Ion Channels at the Nucleus： Electrophysiology Meets the Genome

The nuclear envelope is increasingly viewed from an electrophysiological perspective by researchers interested in signal transduction pathways that influence gene transcription and other processes in the nucleus. Here, we describe evidence for ion channels and transporters in the nuclear membranes and for possible ion gating by the nuclear pores. We argue that a systems-level understanding of cellular regulation is likely to require the assimilation of nuclear electrophysiology into molecular and biochemical signaling pathways.

CLINICAL VISUAL ELECTROPHYSIOLOGY IN CHINA

With the development of modern ophthalmology in thepast 40 years, great progress has been made in visual electrophysiology in terms of clinical application, basic re-search and academic exchange in China. A series of visual electrophysiological measurements, such as electroretinography(ERG), evoked early response (ERP), electrooculography (EOG), visual evoked potential (VEP), which are assisted withvarious stimuli and computer analysis, have been used in test-ing different layers of the visual system. Some new relevanttechniques have been developed and the academic organizationsestablished. These demonstrate that clinical visual physiologyhas entered a new period of development.

On the electrophysiology of the atrial fast conduction system:an uncertain quantification study

Cardiac modeling entails the epistemic uncertainty of the input parameters,such as bundles and chambers geometry,electrical conductivities and cell parameters,thus calling for an uncertainty quantification(UQ)analysis.Since the cardiac activation and the subsequent muscular contraction is provided by a complex electrophysiology system made of interconnected conductive media,we focus here on the fast conductivity structures of the atria(internodal pathways)with the aim of identifying which of the uncertain inputs mostly influence the propagation of the depolarization front.Firstly,the distributions of the input parameters are calibrated using data available from the literature taking into account gender differences.The output quantities of interest(Qols)of medical relevance are defined and a set of metamodels(one for each Qol)is then trained according to a polynomial chaos expansion(PCE)in order to run a global sensitivity analysis with non-linear variance-based SoboF indices with confidence intervals evaluated through the bootstrap method.The most sensitive parameters on each Qol are then identified for both genders showing the same order of importance of the model inputs on the electrical activation.Lastly,the probability distributions of the Qols are obtained through a forward sensitivity analysis using the same trained metamodels.It results that several input parameters-including the position of the internodal pathways and the electrical impulse applied at the sinoatrial node一have a little influence on the Qols studied.Vice-versa the electrical activation of the atrial fast conduction system is sensitive on the bundles geometry and electrical conductivities that need to be carefully measured or calibrated in order for the electrophysiology model to be accurate and predictive.

Effects of irbesartan on atrial cell electrophysiology

Atrial fibrillation (AF) is the most common sustained arrhythmia encounteredin clinical practice.1 Its incidence increases with age and the presence of structural heartdisease. It is a major cause of stroke, especially in the elderly. It has been shown thatangiotensin converting enzyme inhibitor (ACEI) can reduce the incidence of AF after acute myocardialinfarction.2 Several studies have shown that activation of the rennin-angiotensin system isassociated with the mechanisms of AF. Irbesartan is a long-acting angiotensin II type 1 receptorantagonist used widely in the treatment of hypertension.3 In recent years, it has been demonstratedthat patients treated with amiodarone plus irbesartan had a lower rate of recurrence of atrialfibrillation than did patients treated with amiodarone alone.4 These findings suggest that theinhibition of angiotensin II may prevent AF, but its underlying electrophysiological mechanisms areobscure. The purpose of this study is to investigate the effects of irbesartan on atrial cellelectrophysiology.

Advances in micro-nano biosensing platforms for intracellular electrophysiology

The establishment of a dependable electrophysiological detection platform is paramount for cardiology and neuroscience research.In the past decade,devices based on micro and nanoscale sensing and control technologies have been developed to construct electrophysiological platforms.Their unique morphological advantages and novel processing methods offer the potential for high-throughput,high-fidelity electrical signal recording.In this review,we analyze the structure,transmembrane strategies,and electrophysiological detection methods of active/passive micro and nano sensing platforms.We also provide an outlook on their vast potential for development in light of the opportunities and challenges facing micro and nano sensing technology,with the aim of pushing for higher-level electrophysiological platform construction to meet the needs of experimental research and clinical applications.