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Abstract Chronic heavy alcohol use is associated with lethal arrhythmias. Whether common East Asian-specific aldehyde dehydrogenase deficiency (ALDH2*2) contributes to arrhythmogenesis caused by low level alcohol use remains unclear. Here we show 59 habitual alcohol users carrying ALDH2 rs671 have longer QT interval (corrected) and higher ventricular tachyarrhythmia events compared with 137 ALDH2 wild-type (Wt) habitual alcohol users and 57 alcohol non-users. Notably, we observe QT prolongation and a higher risk of premature ventricular contractions among human ALDH2 variants showing habitual light-to-moderate alcohol consumption. We recapitulate a human electrophysiological QT prolongation phenotype using a mouse ALDH2*2 knock-in (KI) model treated with 4% ethanol, which shows markedly reduced total amount of connexin43 albeit increased lateralization accompanied by markedly downregulated sarcolemmal Nav1.5, Kv1.4 and Kv4.2 expressions compared to EtOH-treated Wt mice. Whole-cell patch-clamps reveal a more pronounced action potential prolongation in EtOH-treated ALDH2*2 KI mice. By programmed electrical stimulation, rotors are only provokable in EtOH-treated ALDH2*2 KI mice along with higher number and duration of ventricular arrhythmia episodes. The present research helps formulate safe alcohol drinking guideline for ALDH2 deficient population and develop novel protective agents for these subjects.

Abstract Optogenetics is an emerging biological approach with the unique capability of specific targeting due to the precise light control with high spatial and temporal resolution. It uses selected light wavelengths to control and modulate the biological functions of cells, tissues, and organ levels. Optogenetics has been instrumental in different biomedical applications, including neuroscience, diabetes, and mitochondria, based on distinctive optical biomedical effects with light modulation. Nowadays, optogenetics in cardiology is rapidly evolving for the understanding and treatment of cardiovascular diseases. Several in vitro and in vivo research for cardiac optogenetics demonstrated visible progress. The optogenetics technique can be applied to address critical cardiovascular problems such as heart failure and arrhythmia. To this end, this paper reviews cardiac electrophysiology and the technical progress about experimental and clinical cardiac optogenetics and provides the background and evolution of cardiac optogenetics. We reviewed the literature to demonstrate the servo type, transfection efficiency, signal recording, and heart disease targets in optogenetic applications. Such literature review would hopefully expedite the progress of optogenetics in cardiology and further expect to translate into the clinical terminal in the future.

Background: The skin sympathetic nerve activity (SKNA) is a new method to measure sympathetic nerve activity by using conventional ECG electrodes. We developed a novel approach to analyze the complexity of SKNA time series under different time scales and showed its prognostic significance in patients receiving critical care. Methods: This study measured SKNA in patients admitted to an intensive care unit (ICU). Each recording is 10-minute long with 10000Hz sampling rate. Multi-scale fluctuation analysis (MSFA) was developed to quantify the variation within each time scale after removing the linear trend. The prognostic value of SKNA was combined with traditional prognostics scoring system to improve the predictive values. Results: 155 patients were recruited. After 30 and 90 days, 30 and 48 patients expired. MSFA was significantly higher in survival group than mortality group for 30-day (0.487 ± 0.185 vs 0.401 ± 0.045, p = 0.018) and 90-day (0.499 ± 0.196 vs 0.414 ± 0.061, p = 0.001) follow-up. Sequential Organ Failure Assessment (SOFA) score was significantly lower in the survival group compared to the expired group for 30-day and 90-day (4.1 ± 2.9 vs. 5.5 ± 4.1, p = 0.032 and 3.9 ± 3.0 vs. 5.4 ± 3.5, p = 0.012). The Kaplan–Meier survival analysis showed MSFA lower than 0.401 (log-rank test:4.96, p = 0.03) or with SOFA score lower than 5 (log-rank test:5.49, p = 0.019) have a significantly higher mortality rate. A multivariate Cox regression model showed that the MSFA is an independent predictor for 30-day mortality (HR = 2.35, 1.08–5.09, p = 0.031) and 90-day mortality (HR = 1.96, 1.08–3.58, p = 0.027). Conclusion: MSFA was a significant prognostic predictor for critically ill patients. MSFA adding to SOFA score could help improve risk prediction.

Abstract Electrocardiogram (ECG)-based intelligent screening for systolic heart failure (HF) is an emerging method that could become a low-cost and rapid screening tool for early diagnosis of the disease before the comprehensive echocardiographic procedure. We collected 12-lead ECG signals from 900 systolic HF patients (ejection fraction, EF

Abstract Aims Hypertension is a significant risk for the development of left ventricular hypertrophy, diastolic dysfunction, followed by heart failure and sudden cardiac death. While therapy with sacubitril/valsartan (SV) reduces the risk of sudden cardiac death in patients with heart failure and systolic dysfunction, the effect on those with diastolic dysfunction remains unclear. We hypothesized that, in the animal model of hypertensive heart disease, treatment with SV reduces the susceptibility to ventricular arrhythmia. Methods and results Young adult female spontaneous hypertensive rats (SHRs) were randomly separated into three groups, which were SHRs, SHRs treated with valsartan, and SHRs treated with SV. In addition, the age‐matched and weight‐matched Wistar Kyoto rats were considered as controls, and there were 12 rats in each group. In vivo ventricular tachyarrhythmia induction and in vitro optical mapping were used to measure the inducibility of ventricular arrhythmias and to characterize the dynamic properties of electrical propagation. The level of small‐conductance Ca2+‐activated potassium channel type 2 (KCNN2) was analysed in cardiac tissue. Compared with SHR with left ventricular hypertrophy, treatment with SV significantly improved cardiac geometry (relative wall thickness, 0.68 ± 0.11 vs. 0.76 ± 0.13, P

Background: Wearable and unobtrusive sensing devices are rapidly evolving for long-term cardiovascular monitoring. However, most of the cardiovascular device requires multi-channel physiological signals acquisition, especially in continuous blood pressure (BP) measurement using pulse transition time (PTT) based methods. The multi-devices implementation could impede wearable applications. Objective: This study developed a wearable neck patch device using single-channel impedance plethysmography (IPG) sensing for cardiovascular monitoring, including continuous BP and heart rate (HR) measurement. Methods: IPG-based BP model was derived based on the Bramwell-Hill equation. A patch IPG device was designed and installed above the carotid artery of the subject neck. To validate the BP and HR functions of our device, the Bland-Altman plots were performed to evaluate the estimation error between the reference and the proposed devices within 20 healthy subjects. Results: The BP performance indicates that systolic BP (SBP) estimation error was -0.16 ± 2.97 mmHg and 2.43 ± 1.71 mmHg in terms of mean error (ME) and mean absolute error (MAE), and 0.09 ± 3.30 mmHg and 2.83 ± 1.68 mmHg for diastolic BP (DBP) estimation. Moreover, the HR accuracy has the ME and MAE of 0.02 ± 0.17 bpm and 0.14 ± 0.08 bpm; mean percentage error (MPE) and mean absolute percentage error (MAPE) obtained 0.04 ± 0.23 % and 0.19 ± 0.12 %. Based on statistical results, the BP and HR function of our device satisfied with AAMI/ANSI criteria below 5 ± 8 mmHg and ± 5 bpm or ± 10%. Conclusion: This study implemented a wearable neck patch device with single-channel IPG acquisition that provided two significant cardiovascular parameters of continuous BP and HR, and its performance agreed with standard criteria based on validation with reference sensors. Significance: The proposed proof-of-concept IPG neck patch device has a high potential for wearable applications and low-cost manufacturing in cardiovascular monitoring.

Backgrounds: Acute myocardial infarction (AMI) affects the autonomic nervous system (ANS) function. The aim of our study is to detect the particular patterns of ANS regulation in AMI. We hypothesize that altered ANS regulation in AMI patients causes synchronized neural discharge (clustering phenomenon) detected by non-invasive skin sympathetic nerve activity (SKNA).Methods: Forty subjects, including 20 AMI patients and 20 non-AMI controls, participated in the study. The wide-band bioelectrical signals (neuECG) were continuously recorded on the body surface for 5 min. SKNA was signal processed to depict the envelope of SKNA (eSKNA). By labeling the clusters, the AMI subjects were separated into non-AMI, non-cluster appearing (AMINCA), and cluster appearing (AMICA) groups.Results: The average eSKNA was significantly correlated with HRV low-frequency (LF) power (rho = −0.336) and high-frequency power (rho = −0.372). The cross-comparison results demonstrated that eSKNA is a valid surrogate marker to assess ANS in AMI patients. The frequency of cluster occurrence was 0.01–0.03 Hz and the amplitude was about 3 μV. The LF/HF ratio of AMICA (median: 1.877; Q1–Q3: 1.483–2.413) revealed significantly lower than AMINCA (median: 3.959; Q1–Q3: 1.840–6.562). The results suggest that the SKNA clustering is a unique temporal pattern of ANS synchronized discharge, which could indicate the lower sympathetic status (by HRV) in AMI patients.Conclusion: This is the first study to identify SKNA clustering phenomenon in AMI patients. Such a synchronized nerve discharge pattern could be detected with non-invasive SKNA signals. SKNA temporal clustering could be a novel biomarker to classify ANS regulation ability in AMI patients.Clinical and Translational Significance: SKNA is higher in AMI patients than in control and negatively correlates with parasympathetic parameters. SKNA clustering is associated with a lower LF/HF ratio that has been shown to correlate with sudden cardiac death in AMI. The lack of SKNA temporal clustering could indicate poor ANS regulation in AMI patients.

Background: The mechanism of Interleukin-17 (IL-17) induced ventricular arrhythmia (VA) remains unclear. This study aimed to investigate the effect of intracellular calcium (Cai) handling and VA susceptibility by IL-17.Methods: The electrophysiological properties of isolated perfused rabbit hearts under IL-17 (20 ng/ml, N = 6) and the IL-17 with neutralizer (0.4 μg/ml, N = 6) were evaluated using an optical mapping system. The action potential duration (APD) and Cai transient duration (CaiTD) were examined, and semiquantitative reverse transcriptase-polymerase chain reaction analysis of ion channels was performed.Results: There were longer APD80, CaiTD80 and increased thresholds of APD and CaiTD alternans, the maximum slope of APD restitution and induction of VA threshold in IL-17 group compared with those in IL-17 neutralizer and baseline groups. During ventricular fibrillation, the number of phase singularities and dominant frequency were both significantly greater in IL-17 group than in baseline group. The mRNA expressions of the Na+/Ca2+ exchanger, phospholamban, and ryanodine receptor Ca2+ release channel were upregulated, and the subunit of L-type Ca2+ current and sarcoplasmic reticulum Ca2+-ATPase 2a were significantly reduced in IL-17 group compared to baseline and IL-17 neutralizer group.Conclusions: IL-17 enhanced CaiTD and APD alternans through disturbances in calcium handling, which may increase VA susceptibility.

Background Patients with rheumatoid arthritis are at twice the risk of ventricular arrhythmia and sudden cardiac death as the general population. We hypothesize that β‐blocker treatment of rheumatoid arthritis is antiarrhythmic by producing synergistic anticatecholaminergic and anti‐inflammatory effects. Methods and Results Collagen‐induced arthritis (CIA) was induced in Lewis rats by immunization with type II collagen in Freund's incomplete adjuvant. The treatment with propranolol (4 mg/kg) started on the first day of immunization. We evaluated the ventricular vulnerability to ventricular arrhythmia using in vivo programmed stimulation and performed ex vivo optical mapping to measure the electrical remodeling of the heart. The ventricular tissue was further processed for immunohistochemical staining and protein array analysis. The assessment of ventricular vulnerability showed that the number and duration of the induced ventricular arrhythmia episodes were increased in CIA rats, which were improved with propranolol treatment. The sympathovagal index and the plasma level of catecholamines significantly increased in CIA rats, whereas the use of propranolol attenuated sympathetic hyperactivity. In the optical mapping study, electrical remodeling, characterized by prolonged action potential duration, slow conduction velocity, and steepened action‐potential duration restitution, were noted in CIA rats and reversed in the propranolol‐treatment group. The propranolol treatment was associated with decreases in paw thickness, fewer inflammatory cell infiltrations in the heart, reduced levels of cardiac inflammatory cytokines, and less cardiac fibrosis as compared with the CIA group. Conclusions CIA increased ventricular arrhythmia vulnerability through sympathetic hyperinnervation and proarrhythmic ventricular electrophysiological remodeling. Treatment with propranolol in CIA rats was both anti‐inflammatory and antiarrhythmic.

Recent developments in epidemiology have confirmed that airborne particulates are directly associated with respiratory pathology and mortality. Although clinical studies have yielded evidence of the effects of many types of fine particulates on human health, it still does not have a complete understanding of how physiological reactions are caused nor to the changes and damages associated with cellular and molecular mechanisms. Currently, most health assessment studies of particulate matter (PM) are conducted through cell culture or animal experiments. The results of such experiments often do not correlate with clinical findings or actual human reactions, and they also cause difficulty when investigating the causes of air pollution and associated human health hazards, the analysis of biomarkers, and the development of future pollution control strategies. Microfluidic-based cell culture technology has considerable potential to expand the capabilities of conventional cell culture by providing high-precision measurement, considerably increasing the potential for the parallelization of cellular assays, ensuring inexpensive automation, and improving the response of the overall cell culture in a more physiologically relevant context. This review paper focuses on integrating the important respiratory health problems caused by air pollution today, as well as the development and application of biomimetic organ-on-a-chip technology. This more precise experimental model is expected to accelerate studies elucidating the effect of PM on the human body and to reveal new opportunities for breakthroughs in disease research and drug development.

INTRODUCTION:High beat-to-beat morphological variation (divergence) on the ventricular electrogram during programmed ventricular stimulation (PVS) is associated with increased risk of ventricular fibrillation (VF), with unclear mechanisms. We hypothesized that ventricular divergence is associated with epicardial wavebreaks during PVS, and that it predicts VF occurrence. METHOD AND RESULTS:Langendorff-perfused rabbit hearts (n = 10) underwent 30-min therapeutic hypothermia (TH, 30°C), followed by a 20-min treatment with rotigaptide (300 nM), a gap junction modifier. VF inducibility was tested using burst ventricular pacing at the shortest pacing cycle length achieving 1:1 ventricular capture. Pseudo-ECG (p-ECG) and epicardial activation maps were simultaneously recorded for divergence and wavebreaks analysis, respectively. A total of 112 optical and p-ECG recordings (62 at TH, 50 at TH treated with rotigaptide) were analyzed. Adding rotigaptide reduced ventricular divergence, from 0.13±0.10 at TH to 0.09±0.07 (p = 0.018). Similarly, rotigaptide reduced the number of epicardial wavebreaks, from 0.59±0.73 at TH to 0.30±0.49 (p = 0.036). VF inducibility decreased, from 48±31% at TH to 22±32% after rotigaptide infusion (p = 0.032). Linear regression models showed that ventricular divergence correlated with epicardial wavebreaks during TH (p

Electrical defibrillation is a well-established treatment for cardiac dysrhythmias. Studies have suggested that shock-induced spatial sawtooth patterns and virtual electrodes are responsible for defibrillation efficacy. We hypothesize that high-frequency shocks enhance defibrillation efficacy by generating temporal sawtooth patterns and using rapid virtual electrodes synchronized with shock frequency. High-speed optical mapping was performed on isolated rat hearts at 2000 frames/s. Two defibrillation electrodes were placed on opposite sides of the ventricles. An S1-S2 pacing protocol was used to induce ventricular tachyarrhythmia (VTA). High-frequency shocks of equal energy but varying frequencies of 125-1000 Hz were used to evaluate VTA vulnerability and defibrillation success rate. The 1000-Hz shock had the highest VTA induction rate in the shorter S1-S2 intervals (50 and 100 ms) and the highest VTA defibrillation rate (70%) among all frequencies. Temporal sawtooth patterns and synchronous shock-induced virtual electrode responses could be observed with frequencies of up to 1000 Hz. The improved defibrillation outcome with high-frequency shocks suggests a lower energy requirement than that of low-frequency shocks for successful ventricular defibrillation.

Continuous blood pressure (BP) measurement is crucial for long-term cardiovascular monitoring, especially for prompt hypertension detection. However, most of the continuous BP measurements rely on the pulse transit time (PTT) from multiple-channel physiological acquisition systems that impede wearable applications. Recently, wearable and smart health electronics have become significant for next-generation personalized healthcare progress. This study proposes an intelligent single-channel bio-impedance system for personalized BP monitoring. Compared to the PTT-based methods, the proposed sensing configuration greatly reduces the hardware complexity, which is beneficial for wearable applications. Most of all, the proposed system can extract the significant BP features hidden from the measured bio-impedance signals by an ultra-lightweight AI algorithm, implemented to further establish a tailored BP model for personalized healthcare. In the human trial, the proposed system demonstrates the BP accuracy in terms of the mean error (ME) and the mean absolute error (MAE) within 1.7 ± 3.4 mmHg and 2.7 ± 2.6 mmHg, respectively, which agrees with the criteria of the Association for the Advancement of Medical Instrumentation (AAMI). In conclusion, this work presents a proof-of-concept for an AI-based single-channel bio-impedance BP system. The new wearable smart system is expected to accelerate the artificial intelligence of things (AIoT) technology for personalized BP healthcare in the future.

Current research has enabled the use of microphysiological systems and creation of models for alveolar and pulmonary diseases. However, bottlenecks remain in terms of medium- and long-term regulation of cell cultures and their functions in microchannel systems, as well as in the enhancement of in vitro representation of alveolar models and reference values of the data. Currently used systems also require on-chip manufacturing of complex units, such as pumps, tubes, and other cumbersome structures for maintaining cells in culture. In addition, system simplification and minimization of all external and human factors major challenges facing the establishment of in vitro alveolar models. In this study, a magnetically driven dynamic alveolus cell-culture system has been developed to use controlled magnetic force to drive a magnetic film on the chip, thereby directing the fluid within it to produce a circulating flow. The system has been confirmed to be conducive with regard to facilitating uniform attachment of human alveolar epithelial cells and long-term culture. The cell structure has been recapitulated, and differentiation functions have been maintained. Subsequently, reactions between silica nanoparticles and human alveolar epithelial cells have been used to validate the effects and advantages of the proposed dynamic chip-based system compared to a static environment. The innovative concept of use of a magnetic drive has been successfully employed in this study to create a simple and controllable yet dynamic alveolus cell-culture system to realize its functions and advantages with regard to in vitro tissue construction.

Background. LCZ696 (valsartan/sacubitril) therapy significantly reduced mortality in patients with heart failure (HF). Although a clinical trial (PARADISE-MI Trial) has been ongoing to examine the effects of LCZ696 in myocardial infarction (MI) patients, the effects of LCZ696 on remodeling of cardiac electrophysiology in animal models remain largely unclear. Methods. We performed coronary artery ligation to create MI in Sprague-Dawley rats. Echocardiography was performed one week after MI to confirm the development of HF with left ventricular ejection fraction ≤ 40%. MI rats were randomly assigned to receive medical therapy for 4 weeks: LCZ696, enalapril, or vehicle. The sham-operation rats received sham operation without MI creation. In vivo electrophysiological exams were performed under general anesthesia. Western blot analyses were conducted to quantify ion channel proteins. Results. The HF-vehicle group did not show significant changes in LVEF. Both enalapril and LCZ696 therapy significantly improved LVEF. The HF-vehicle group had higher ventricular arrhythmia (VA) inducibility than the sham group. As compared with the HF-vehicle group, LCZ696 therapy significantly reduced VA inducibility, but enalapril therapy did not. Western blot analyses showed significant downregulation of NaV1.5, ERG, KCNE1, and KCNE2 channel proteins in the HF vehicle group compared with the sham group. LCZ696 therapy upregulated protein expression of ERG, KCNE1, and KCNE2. Conclusion. As compared with enalapril therapy, LCZ696 therapy led to improvement of LVEF, reduced VA inducibility, and upregulated expression of K+ channel proteins.

The European Association of Preventive Cardiology Exercise Prescription in Everyday Practice and Rehabilitative Training (EXPERT) tool has been developed for digital training and decision support in cardiovascular disease patients in clinical practice. Exercise prescription recommendation systems for sub-healthy people are essential to enhance this dominant group’s physical ability as well. This study aims to construct a guided exercise prescription system for sub-healthy groups using exercise community data to train an AI model. The system consists of six modules, including three-month suggested exercise mode (3m-SEM), predicted value of rest heart rate (rest HR) difference after following three-month suggested exercise mode (3m-PV), two-month suggested exercise mode (2m-SEM), predicted value of rest HR difference after following two-month suggested exercise mode (2m-PV), one-month suggested exercise mode (1m-SEM) and predicted value of rest HR difference after following one-month suggested exercise mode (1m-PV). A new user inputs gender, height, weight, age, and current rest HR value, and the above six modules will provide the user with a prescription. A four-layer neural network model is applied to construct the above six modules. The AI-enabled model produced 95.80%, 100.00%, and 95.00% testing accuracy in 1m-SEM, 2m-SEM, and 3m-SEM, respectively. It reached 3.15, 2.89, and 2.75 BPM testing mean absolute error in 1m-PV, 2m-PV, and 3m-PV. The developed system provides quantitative exercise prescriptions to guide the sub-healthy group to engage in effective exercise programs.

Continuous hemodynamic monitoring is important for long-term cardiovascular healthcare, especially in hypertension. The impedance plethysmography (IPG) based carotid pulse sensing is a non-invasive diagnosis technique for measuring pulse signals and further evaluating the arterial conditions of the patient such as continuous blood pressure (BP) monitoring. To reach the high-resolution IPG-based carotid pulse detection for cardiovascular applications, this study provides an optimized measurement parameter in response to obvious pulsation from the carotid artery. The influence of the frequency of excitation current, electrode cross-sectional area, electrode arrangements, and physiological site of carotid arteries on IPG measurement resolution was thoroughly investigated for optimized parameters. In this study, the IPG system was implemented and installed on the subject’s neck above the carotid artery to evaluate the measurement parameters. The measurement results within 6 subjects obtained the arterial impedance variation of 2137 mΩ using the optimized measurement conditions, including excitation frequency of 50 kHz, a smaller area of 2 cm2, electrode spacing of 4 cm and 1.7 cm for excitation and sensing functions, and location on the left side of the neck. The significance of this study demonstrates an optimized measurement methodology of IPG-based carotid pulse sensing that greatly improves the measurement quality in cardiovascular monitoring.

Non-invasive continuous blood pressure measurement is an emerging issue that potentially can be applied to cardiovascular disease monitoring and prediction. Recently, many groups have proposed the pulse transition time (PTT) method to estimate blood pressure for long-term monitoring. However, the PTT-based methods for blood pressure estimation are limited by non-specific estimation models and require multiple calibrations. This study aims to develop a low-cost wearable piezoelectric-based system for continuous beat-to-beat blood pressure measurement. The pressure change in the radial artery was extracted by systolic and diastolic feature points in pressure pulse wave (PPW) and the pressure sensitivity of the sensor. The proposed system showed a reliable accuracy of systolic blood pressure (SBP) (mean absolute error (MAE) ± standard deviation (SD) 1.52 ± 0.30 mmHg) and diastolic blood pressure (DBP, MAE ± SD 1.83 ± 0.50), and its performance agreed with standard criteria of MAE within 5 mmHg and SD within ±8 mmHg. In conclusion, this study successfully developed a low-cost, high-accuracy piezoelectric-based system for continuous beat-to-beat SBP and DBP measurement without multiple calibrations and complex regression analysis. The system is potentially suitable for continuous, long-term blood pressure-monitoring applications.

Autophagy is the spontaneous degradation of intracellular proteins and organelles in response to nutrient deprivation. The phagocytosis of iron oxide nanoparticles (IONPs) results in intracellular degradation that can be exploited for use in cancer treatment. Non-invasive magnetic control has emerged as an important technology, with breakthroughs achieved in areas such as magneto-thermal therapy and drug delivery. This study aimed to regulate autophagy in mouse B-lymphoma cells (A20) through the incorporation of IONPs–quantum dots (QDs). We hypothesized that with the application of an external magnetic field after phagocytosis of IONPs–QDs, autophagy of intracellular IONPs–QDs could be regulated in a non-invasive manner and subsequently modulate the regulation of inflammatory responses. The potential of this approach as a cancer treatment method was explored. The application of IONPs and an external magnetic force enabled the non-invasive regulation of cell autophagy and modulation of the self-regulatory function of cells. The combination of non-invasive magnetic fields and nanotechnology could provide a new approach to cancer treatment.

Diabetes has become a chronic metabolic disorder, and the growing diabetes population makes medical care more important. We investigated using a portable and noninvasive contact lens as an ideal sensor for diabetes patients whose tear fluid contains glucose. The key feature is the reversible covalent interaction between boronic acid and glucose, which can provide a noninvasive glucose sensor for diabetes patients. We present a phenylboronic acid (PBA)-based HEMA contact lens that exhibits a reversible swelling/shrinking effect to change its thickness. The difference in thickness can be detected in a picture taken with a smartphone and analyzed using software. Our novel technique offers the following capabilities: (i) non-enzymatic and continuous glucose detection with the contact lens; (ii) no need for an embedded circuit and power source for the glucose sensor; and (iii) the use of a smartphone to detect the change in thickness of the contact lens with no need for additional photo-sensors. This technique is promising for a noninvasive measurement of the glucose level and simple implementation of glucose sensing with a smartphone.

BACKGROUND:L-type calcium current reactivation plays an important role in development of early afterdepolarizations (EADs) and torsades de pointes (TdP). Secondary intracellular calcium (Cai) rise is associated with initiation of EADs. OBJECTIVE:To test whether inhibition of sarcoplasmic reticulum (SR) Ca2+ cycling suppresses secondary Cai rise and genesis of EADs. METHODS:Langendorff perfusion and dual voltage and Cai optical mapping were conducted in 10 rabbit hearts. Atrioventricular block (AVB) was created by radiofrequency ablation. After baseline studies, E4031, SR Ca2+ cycling inhibitors (ryanodine plus thapsigargin) and nifedipine were then administrated subsequently, and the protocols were repeated. RESULTS:At baseline, there was no spontaneous or pacing-induced TdP. After E4031 administration, action potential duration (APD) was significantly prolonged and the amplitude of secondary Cai rise was enhanced, and 7 (70%) rabbits developed spontaneous or pacing-induced TdP. In the presence of ryanodine plus thapsigargin, TdP inducibility was significantly reduced (2 hearts, 20%, p = 0.03). Although APD was significantly prolonged (from 298 ± 30 ms to 457 ± 75 ms at pacing cycle length of 1000 m, p = 0.007) by ryanodine plus thapsigargin, the secondary Cai rise was suppressed (from 8.8 ± 2.6% to 1.2 ± 0.9%, p = 0.02). Nifedipine inhibited TdP inducibility in all rabbit hearts. CONCLUSION:In this AVB and long QT rabbit model, inhibition of SR Ca2+ cycyling reduces the inducibility of TdP. The mechanism might be suppression of secondary Cai rise and genesis of EADs.

Apamin sensitive potassium current (I KAS), carried by the type 2 small conductance Ca(2+)-activated potassium (SK2) channels, plays an important role in post-shock action potential duration (APD) shortening and recurrent spontaneous ventricular fibrillation (VF) in failing ventricles.To test the hypothesis that amiodarone inhibits I KAS in human embryonic kidney 293 (HEK-293) cells.We used the patch-clamp technique to study I KAS in HEK-293 cells transiently expressing human SK2 before and after amiodarone administration.Amiodarone inhibited IKAS in a dose-dependent manner (IC50, 2.67 ± 0.25 µM with 1 µM intrapipette Ca(2+)). Maximal inhibition was observed with 50 µM amiodarone which inhibited 85.6 ± 3.1% of IKAS induced with 1 µM intrapipette Ca(2+) (n = 3). IKAS inhibition by amiodarone was not voltage-dependent, but was Ca(2+)-dependent: 30 µM amiodarone inhibited 81.5±1.9% of I KAS induced with 1 µM Ca(2+) (n = 4), and 16.4±4.9% with 250 nM Ca(2+) (n = 5). Desethylamiodarone, a major metabolite of amiodarone, also exerts voltage-independent but Ca(2+) dependent inhibition of I KAS.Both amiodarone and desethylamiodarone inhibit I KAS at therapeutic concentrations. The inhibition is independent of time and voltage, but is dependent on the intracellular Ca(2+) concentration. SK2 current inhibition may in part underlie amiodarone's effects in preventing electrical storm in failing ventricles.