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1.
Biosens Bioelectron ; 179: 113060, 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33571936

RESUMO

BACKGROUND: Electrophysiological sensing of cardiomyocytes (CMs) in optogenetic preparations applies various techniques, such as patch-clamp, microelectrode array, and optical mapping. However, challenges remain in decreasing the cost, system dimensions, and operating skills required for these technologies. OBJECTIVE: This study developed a low-cost, portable impedance plethysmography (IPG)-based electrophysiological measurement of cultured CMs for optogenetic applications. METHODS: To validate the efficacy of the proposed sensor, optogenetic stimulation with different pacing cycle lengths (PCL) was performed to evaluate whether the channelrhodopsin-2 (ChR2)-expressing CM beating rhythm measured by the IPG sensor was consistent with biological responses. RESULTS: The experimental results show that the CM field potential was synchronized with external optical pacing with PCLs ranging from 250 ms to 1000 ms. Moreover, irregular fibrillating waveforms induced by CM arrhythmia were detected after overdrive optical pacing. Through the combined evidence of the theoretical model and experimental results, this study confirmed the feasibility of long-term electrophysiological sensing for optogenetic CMs. CONCLUSION: This study proposes an IPG-based sensor that is low-cost, portable, and requires low-operating skills to perform real-time CM field potential measurement in response to optogenetic stimulation. SIGNIFICANCE: This study demonstrates a new methodology for convenient electrophysiological sensing of CMs in optogenetic applications.

2.
Sci Rep ; 11(1): 1948, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33479367

RESUMO

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 < 50%) and 900 individuals with normal EF in the absence of HF symptoms. The 12-lead ECG signals were converted by continuous wavelet transform (CWT) to 2D spectra and classified using a 2D convolutional neural network (CNN). The 2D CWT spectra of 12-lead ECG signals were trained separately in 12 identical 2D-CNN models. The 12-lead classification results of the 2D-CNN model revealed that Lead V6 had the highest accuracy (0.93), sensitivity (0.97), specificity (0.89), and f1 scores (0.94) in the testing dataset. We designed four comprehensive scoring methods to integrate the 12-lead classification results into a key diagnostic index. The highest quality result among these four methods was obtained when Leads V5 and V6 of the 12-lead ECG signals were combined. Our new 12-lead ECG signal-based intelligent screening method using straightforward combination of ECG leads provides a fast and accurate approach for pre-screening for systolic HF.

3.
Heart Rhythm ; 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33246037

RESUMO

BACKGROUND: Sympathetic nerve activity (SNA), heart rate (HR) and blood pressure (BP) all have very low frequency (VLF), low frequency (LF) and high frequency (HF) oscillations. OBJECTIVE: To test the hypotheses that the frequency spectra of the subcutaneous nerve activity (ScNA), stellate ganglion nerve activity (SGNA), HR and BP are important to cardiac arrhythmogenesis. METHODS: We used radiotransmitters to record SGNA, ScNA, HR and BP in 6 ambulatory dogs and determined the dominant frequency and PAT episodes in 3-min windows over a 24-hr period. RESULTS: The frequency spectra determined in the ScNA reflected that in the SGNA. HF oscillations were present in both ScNA and SGNA at all time but could be overshadowed by the much larger LF and VLF burst activities. The dominant frequency could occur in any of the 3 frequency bands. There were circadian variations with more frequent occurrences of the HF oscillations at night. The HF oscillations in HR and BP matched the HF oscillations in SGNA and ScNA. PATs occurred only when dominant frequencies of SGNA and ScNA were in the LF and VLF bands. CONCLUSIONS: The HF oscillations in BP and HR correlate with the HF oscillations in SNA and are present at all time. HF oscillations can be overshadowed by the much larger LF and VLF burst activities. The PATs only occur when LF or VLF but not when HF is the dominant frequency. The frequency spectra determined in the ScNA reflect that in the SGNA.

4.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 2614-2617, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018542

RESUMO

The main goal of this research is to evaluate the defibrillation efficacy with the high-frequency waveform on ventricular fibrillation in small animals. A biphasic defibrillator with adjustable frequency was designed for this study. This custom-designed defibrillator can be adjusted to generate four different frequencies of 125, 250, 500, and 1000 Hz. Six rat hearts were induced VT/VF by electrical induction using the waveform of these four frequencies. Success VT/VF-induction by applying those four frequencies were recorded and observed by optical mapping. The results showed that the VT/VF-induction success rate is increasing along with higher frequencies. The VT/VF-induction success rate is 16% in 125Hz and 250 Hz, 33% in 500 Hz, and 100% in 1000 Hz with S1-S2 protocol at 100 ms coupling interval. Also, using optical mapping technique, shock-induced optical potential showed that only high-frequency waveform exhibited the largest tissue responses in the middle position of the heart. In conclusion, high-frequency (1000Hz) defibrillation waveform has the highest defibrillation efficacy comparing to other lower frequencies used in this study.


Assuntos
Coração , Fibrilação Ventricular , Animais , Desfibriladores , Eletricidade , Masculino , Ratos , Registros , Fibrilação Ventricular/terapia
5.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 4337-4340, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018955

RESUMO

The function of the autonomic nervous system (ANS) influences most of the physiological mechanisms. The popular non-invasive method to estimate the activities of the autonomic nervous system (ANS) is the heart rate variability (HRV). However, the HRV cannot provide real-time information of the ANS function. The skin sympathetic nerve activity (SKNA) is a novel method to evaluate sympathetic nerve system (SNS) activity. The SKNA technique has shown promise in clinical applications but is limited to evaluating SNS activities. To date, a direct non-invasive method for measuring the parasympathetic nerve system (PNS) function is urgently needed. According to anatomy, the auricular branch of the vagus nerve (aVN) is near the concha surface. In this study, we hypothesize that we can measure the aVN activity (aVNA) with the same technique developed for SKNA recording. Flexible auricular electrodes were developed for continuous long-term recording of aVN activity. The SKNA and aVNA were simultaneously recorded during the experiment. The cold face test and cold pressor test were performed to physiologically activate ANS. The SKNA and aVNA can be obtained simultaneously, and they are correlated with the heart rate change during the physiological challenge. The aVNA has a high potential to be developed into a novel method to measure the PNS activity.


Assuntos
Sistema Nervoso Parassimpático , Nervo Vago , Sistema Nervoso Autônomo , Frequência Cardíaca , Humanos , Sistema Nervoso Simpático
6.
J Am Heart Assoc ; 9(18): e016084, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32865101

RESUMO

Background Patients with rheumatoid arthritis are at twice the risk of ventricular arrhythmia and sudden cardiac death as the general population. We hypothesize that ß-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.

7.
ESC Heart Fail ; 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32969191

RESUMO

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 < 0.05) and diastolic dysfunction (isovolumetric relaxation time, 59.4 ± 3.2 vs. 70.5 ± 4.2 ms, P < 0.05; deceleration time of mitral E wave, 46 ± 4.8 vs. 42 ± 3.8, P < 0.05). The incidence of induced ventricular arrhythmia was significantly reduced in SHR treated with SV compared with SHR (ventricular tachycardia, 1.14 ± 0.32 vs. 2.91 ± 0.5 episodes per 10 stimuli, P < 0.001; ventricular fibrillation, 1.72 ± 0.31 vs. 5.81 ± 0.42 episodes per 10 stimuli, P < 0.001). The prolonged action potential duration (APD) and increase of the maximum slope of APD restitution were observed in SHR, while the treatment of SV improved the arrhythmogeneity (APD, 37.12 ± 6.18 vs. 92.41 ± 10.71 ms at 250 ms pacing cycle length, P < 0.001; max slope 0.29 ± 0.01 vs. 1.48 ± 0.04, P < 0.001). These effects were strongly associated with down-regulation of KCNN2 (0.38 ± 0.07 vs. 0.74 ± 0.12 ng/ml, P < 0.001). The treatment of SV also decreased the level of N-terminal pro-B-type natriuretic peptide, cardiac bridging integrator-1, and intramyocardial fibrosis of SHR. CONCLUSIONS: In conclusion, synergistic blockade of the neprilysin and the renin-angiotensin system by SV in SHRs results in KCNN2-associated electrical remodelling in ventricle, which stabilizes electrical dynamics and attenuates arrhythmogenesis.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32946036

RESUMO

PURPOSE: Ventricular arrhythmia (VA) is related to inflammatory activity. Rhodiola crenulate (RC) and its main active component, salidroside, have been reported as anti-inflammatory agents. The aim of this study was to demonstrate the effect of RC and salidroside in preventing VA via the inhibition of IL-17 in an ischemic heart failure (HF) model. METHODS: Rabbit HF models were established by coronary artery ligation for 4 weeks. These rabbits were treated with RC (125, 250, 500 mg/kg) and salidroside (9.5 mg/kg) once every 2 days for 4 weeks. WBC, serum biochemistry, ECG, and the expression of CD4+ T cells were measured every 2 weeks. The mRNA and protein expressions of IL-17 were measured by real time-PCR, ELISA, and Western blotting after RC and salidroside treatment for 4 weeks. Open-chest epicardial catheter stimulation was performed for VA provocation. RESULTS: After RC and salidroside treatment in HF left ventricle, (1) the levels of WBC and CD4+ T cells decreased, (2) the expression of IL-17 and its downstream target genes, IL-6, TNF-α, IL-1ß, IL-8, and CCL20, reduced, (3) the level of NLRP3 inflammasome was decreased, (4) fibrosis and collagen production were significantly downregulated, (5) p38 MAPK and ERK1/2 phosphorylation were attenuated, (6) the inducibility of VA was decreased, and (7) the levels of Kir2.1, Nav1.5, NCX, PLB, SERCA2a and RyR were up-regulated. CONCLUSIONS: RC inhibited the expression of IL-17 and its downstream target genes that were mediated by activation of several MAPKs, which decreased the levels of fibrosis and apoptosis and suppressed VA.

9.
J Formos Med Assoc ; 2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32741736

RESUMO

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.

10.
Eur J Cardiothorac Surg ; 58(5): 915-922, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32584984

RESUMO

OBJECTIVES: Serial lactate (clearance) data are commonly used for risk stratification in patients receiving veno-arterial extracorporeal life support (ECLS). METHODS: We retrospectively analysed 855 patients who had undergone ECLS due to cardiac (n = 578) and non-cardiac (n = 277) aetiologies between 2002 and 2013 at National Taiwan University Hospital. Serial lactate (clearance) data were collected before ECLS and at 8, 16, 24, 48 and 72 h after ECLS. To investigate the impact of lactate (clearance) levels on 180-day survival, we performed linear mixed model and joint model analyses using the Bayesian approach. RESULTS: Among the 855 patients, 564 (65.9%) patients died within 180 days after ECLS cannulation. The joint model showed that the effect of lactate on survival was null in both the reduced model and the fully adjusted model. However, an effect of lactate clearance on survival was observed in the reduced model [estimate 0.004; 95% confidence interval (CI) 0.002-0.006] and the fully adjusted model (estimate 0.003; 95% CI 0.001-0.005). In a further secondary analysis, lactate clearance (hazard ratio 0.861; 95% CI 0.813-0.931) at 16 h after ECLS cannulation was determined to be a risk factor for mortality. According to a receiver operating characteristic curve analysis, the SAVE score combined with lactate clearance (area under curve = 0.881) showed good outcome discrimination. CONCLUSIONS: Incorporating lactate clearance at 16 h after ECLS cannulation into the SAVE system improved the predictive value for mortality in patients receiving ECLS.

11.
Artigo em Inglês | MEDLINE | ID: mdl-32548105

RESUMO

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.

12.
PLoS One ; 15(5): e0232529, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32357163

RESUMO

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.


Assuntos
Cardioversão Elétrica/métodos , Taquicardia Ventricular/terapia , Fibrilação Ventricular/terapia , Animais , Modelos Animais de Doenças , Eletrodos , Fenômenos Eletrofisiológicos , Feminino , Ventrículos do Coração/fisiopatologia , Técnicas In Vitro , Modelos Cardiovasculares , Ratos , Ratos Sprague-Dawley , Taquicardia Ventricular/fisiopatologia , Interface Usuário-Computador , Fibrilação Ventricular/fisiopatologia , Função Ventricular , Imagens com Corantes Sensíveis à Voltagem/instrumentação , Imagens com Corantes Sensíveis à Voltagem/métodos
13.
Int J Mol Sci ; 21(8)2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32331417

RESUMO

Retinal prosthesis has recently emerged as a treatment strategy for retinopathies, providing excellent assistance in the treatment of age-related macular degeneration (AMD) and retinitis pigmentosa. The potential application of graphene oxide (GO), a highly biocompatible nanomaterial with superior physicochemical properties, in the fabrication of electrodes for retinal prosthesis, is reviewed in this article. This review integrates insights from biological medicine and nanotechnology, with electronic and electrical engineering technological breakthroughs, and aims to highlight innovative objectives in developing biomedical applications of retinal prosthesis.

14.
Nat Protoc ; 15(5): 1853-1877, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32313253

RESUMO

neuECG, the simultaneous noninvasive recording of ECG and skin sympathetic nerve activity (SKNA), directly records sympathetic nerve activity over a long period of time. It can be used to measure sympathetic tone in healthy subjects and in subjects with non-cardiovascular diseases. The electrical activity that can be measured on the surface of the skin originates from the heart, the muscle or nerve structures. Because the frequency content of nerve activity falls in a higher frequency range than that of the ECG and myopotential, it is possible to use high-pass or band-pass filtering to specifically isolate the SKNA. neuECG is voltage calibrated and does not require invasive procedures to impale electrodes in nerves and thus has advantages over microneurography. Here, we present a protocol that takes <10 min to set up. The neuECG can be continuously recorded over a 24-h period or longer. We also describe methods to efficiently analyze neuECG from humans using commercially available hardware and software to facilitate adoption of this technology in clinical research.


Assuntos
Técnicas de Diagnóstico Neurológico , Eletrocardiografia , Sistema Nervoso Simpático , Voluntários Saudáveis , Humanos , Pele/inervação
15.
J Card Fail ; 26(6): 527-537, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32209390

RESUMO

BACKGROUND: Coronary artery disease is the most common cause of heart failure (HF) in developed countries. The aim of this study was to elucidate the mechanisms of reduction of arrhythmias after sacubitril/valsartan (LCZ696) therapy in a myocardial infarction (MI)-HF rabbit model. METHODS AND RESULTS: Chronic MI in rabbits with HF were divided into 3 groups: placebo control, valsartan 30 mg/day and LCZ696 60 mg/day. After 4 weeks of therapy, an electrophysiologic study and a dual voltage-calcium optical mapping study were performed. The LCZ696 group had significantly better left ventricular ejection fraction and lower ventricular tachyarrhythmia inducibility than the valsartan and placebo groups. The most common ventricular tachyarrhythmia pattern was 1 or 2 ectopic beats originating from the peri-infarct areas, followed by re-entrant beats surrounding phase singularity points. Compared to the valsartan and placebo groups, the LCZ696 group had significantly shorter action-potential duration, shorter intracellular calcium tau constant, faster conduction velocity, and shorter pacing cycle length to induce arrhythmogenic alternans. LCZ696 therapy reduced the phosphorylated calmodulin-dependent protein kinase II (CaMKII-p) expression. CONCLUSIONS: In a rabbit model with chronic MI and HF, LCZ696 therapy ameliorated postinfarct heart function impairment and electrophysiologic remodeling and altered CaMKII-p expression, leading to reduced ventricular tachyarrhythmia inducibility.

16.
Sensors (Basel) ; 20(3)2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32033495

RESUMO

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.

17.
PLoS One ; 15(2): e0228818, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32084145

RESUMO

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<0.001). CONCLUSION: Ventricular divergence correlated with, and might be predictive of epicardial wavebreaks during PVS at TH. Rotigaptide decreased both the ventricular divergence and epicardial wavebreaks, and reduced the probability of pacing-induced VF during TH.


Assuntos
Arritmias Cardíacas/fisiopatologia , Ventrículos do Coração/fisiopatologia , Hipotermia Induzida/efeitos adversos , Pericárdio/fisiologia , Animais , Eletrocardiografia , Ventrículos do Coração/efeitos dos fármacos , Oligopeptídeos/farmacologia , Pericárdio/efeitos dos fármacos , Pericárdio/fisiopatologia , Coelhos
18.
J Am Coll Cardiol ; 75(1): 1-13, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31918815

RESUMO

BACKGROUND: The presence and significance of neural remodeling in premature ventricular contraction-induced cardiomyopathy (PVC-CM) remain unknown. OBJECTIVES: This study aimed to characterize cardiac sympathovagal balance and proarrhythmia in a canine model of PVC-CM. METHODS: In 12 canines, the investigators implanted epicardial pacemakers and radiotelemetry units to record cardiac rhythm and nerve activity (NA) from the left stellate ganglion (SNA), left cardiac vagus (VNA), and arterial blood pressure. Bigeminal PVCs (200 ms coupling) were applied for 12 weeks to induce PVC-CM in 7 animals then disabled for 4 weeks to allow complete recovery of left ventricular ejection fraction (LVEF), versus 5 sham controls. RESULTS: After 12 weeks of PVCs, LVEF (p = 0.006) and dP/dT (p = 0.007) decreased. Resting SNA (p = 0.002) and VNA (p = 0.04), exercise SNA (p = 0.01), SNA response to evoked PVCs (p = 0.005), heart rate (HR) at rest (p = 0.003), and exercise (p < 0.04) increased, whereas HR variability (HRV) decreased (p = 0.009). There was increased spontaneous atrial (p = 0.02) and ventricular arrhythmias (p = 0.03) in PVC-CM. Increased SNA preceded both atrial (p = 0.0003) and ventricular (p = 0.009) arrhythmia onset. Clonidine suppressed SNA and abolished all arrhythmias. After disabling PVC for 4 weeks, LVEF (p = 0.01), dP/dT (p = 0.047), and resting VNA (p = 0.03) recovered to baseline levels. However, SNA, resting HR, HRV, and atrial (p = 0.03) and ventricular (p = 0.03) proarrhythmia persisted. There was sympathetic hyperinnervation in stellate ganglia (p = 0.02) but not ventricles (p = 0.2) of PVC-CM and recovered animals versus sham controls. CONCLUSIONS: Neural remodeling in PVC-CM is characterized by extracardiac sympathetic hyperinnervation and sympathetic neural hyperactivity that persists despite normalization of LVEF. The altered cardiac sympathovagal balance is an important trigger and substrate for atrial and ventricular proarrhythmia.


Assuntos
Cardiomiopatias/fisiopatologia , Contração Miocárdica/fisiologia , Recuperação de Função Fisiológica/fisiologia , Complexos Ventriculares Prematuros/fisiopatologia , Remodelação Ventricular/fisiologia , Animais , Cardiomiopatias/diagnóstico por imagem , Cães , Ecocardiografia/métodos , Eletrocardiografia/métodos , Frequência Cardíaca/fisiologia , Complexos Ventriculares Prematuros/diagnóstico por imagem
19.
Heart Rhythm ; 17(2): 332-340, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31513946

RESUMO

BACKGROUND: Ondansetron, a widely prescribed antiemetic, has been implicated in drug-induced long QT syndrome. Recent patch clamp experiments have shown that ondansetron inhibits the apamin-sensitive small conductance calcium-activated potassium current (IKAS). OBJECTIVE: The purpose of this study was to determine whether ondansetron causes action potential duration (APD) prolongation by IKAS inhibition. METHODS: Optical mapping was performed in rabbit hearts with pacing-induced heart failure (HF) and in normal hearts before and after ondansetron (100 nM) infusion. APD at 80% repolarization (APD80) and arrhythmia inducibility were determined. Additional studies with ondansetron were performed in normal hearts perfused with hypokalemic Tyrode's (2.4 mM) solution before or after apamin administration. RESULTS: The corrected QT interval in HF was 326 ms (95% confidence interval [CI] 306-347 ms) at baseline and 364 ms (95% CI 351-378 ms) after ondansetron infusion (P < .001). Ondansetron significantly prolonged APD80 in the HF group and promoted early afterdepolarizations, steepened the APD restitution curve, and increased ventricular vulnerability. Ventricular fibrillation was not inducible in HF ventricles at baseline, but after ondansetron infusion, ventricular fibrillation was induced in 5 of the 7 ventricles (P = .021). In hypokalemia, apamin prolonged APD80 from 163 ms (95% CI 146-180 ms) to 180 ms (95% CI 156-204 ms) (P = .018). Subsequent administration of ondansetron failed to further prolong APD80 (180 ms [95% CI 156-204 ms] vs 179 ms [95% CI 165-194 ms]; P = .789). The results were similar when ondansetron was administered first, followed by apamin. CONCLUSION: Ondansetron is a specific IKAS blocker at therapeutic concentrations. Ondansetron may prolong the QT interval in HF by inhibiting small conductance calcium-activated potassium channels, which increases the vulnerability to ventricular arrhythmias.

20.
Heart Rhythm ; 17(5 Pt A): 804-812, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31605791

RESUMO

BACKGROUND: Autonomic imbalance is the proposed mechanism of syncope during a tilt table test (TTT). We have recently demonstrated that skin sympathetic nerve activity (SKNA) can be noninvasively recorded using electrocardiographic electrodes. OBJECTIVE: The purpose of this study was to test the hypothesis that increased SKNA activation precedes tilt-induced syncope. METHODS: We studied 50 patients with a history of neurocardiogenic syncope undergoing a TTT. The recorded signals were band-pass filtered at 500-1000 Hz to analyze nerve activity. RESULTS: The average SKNA (aSKNA) value at baseline was 1.38 ± 0.38 µV in patients without syncope and 1.42 ± 0.52 µV in patients with syncope (P = .77). On upright tilt, aSKNA was 1.34 ± 0.40 µV in patients who did not have syncope and 1.39 ± 0.43 µV in patients who had syncope (P = .65). In all 14 patients with syncope, there was a surge of SKNA before an initial increase in heart rate followed by bradycardia, hypotension, and syncope. The peak aSKNA immediately (<1 minute) before syncope was significantly higher than baseline aSKNA (2.63 ± 1.22 vs 1.39 ± 0.43 µV; P = .0005). After syncope, patients were immediately placed in the supine position and aSKNA dropped significantly to 1.26 ± 0.43 µV; (P = .0004). The heart rate variability during the TTT shows a significant increase in parasympathetic tone during syncope (low-frequency/high-frequency ratio: 7.15 vs 2.21; P = .04). CONCLUSION: Patients with syncope do not have elevated sympathetic tone at baseline or during the TTT except immediately before syncope when there is a transient surge of SKNA followed by sympathetic withdrawal along with parasympathetic surge.

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