ResearchPad - electrophysiology https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Early correction of synaptic long-term depression improves abnormal anxiety-like behavior in adult GluN2B-C456Y-mutant mice]]> https://www.researchpad.co/article/elastic_article_13831 Mice that carry a heterozygous, autism spectrum disorder-risk C456Y mutation in the NMDA receptor (NMDAR) subunit GluN2B show decreased protein levels, hippocampal NMDAR currents, and NMDAR-dependent long-term depression and have abnormal anxiolytic-like behavior. Early, but not late, treatment of the young mice with the NMDAR agonist D-cycloserine rescues these phenotypes.

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<![CDATA[Inferring a simple mechanism for alpha-blocking by fitting a neural population model to EEG spectra]]> https://www.researchpad.co/article/elastic_article_13836 One of the most striking features of the human electroencephalogram (EEG) is the presence of neural oscillations in the range of 8-13 Hz. It is well known that attenuation of these alpha oscillations, a process known as alpha blocking, arises from opening of the eyes, though the cause has remained obscure. In this study we infer the mechanism underlying alpha blocking by fitting a neural population model to EEG spectra from 82 different individuals. Although such models have long held the promise of being able to relate macroscopic recordings of brain activity to microscopic neural parameters, their utility has been limited by the difficulty of inferring these parameters from fits to data. Our approach involves fitting eyes-open and eyes-closed EEG spectra in a way that minimizes unnecessary differences in model parameters between the two states. Surprisingly, we find that changes in just one parameter, the level of external input to the inhibitory neurons in cortex, is sufficient to explain the attenuation of alpha oscillations. This indicates that opening of the eyes reduces alpha activity simply by increasing external inputs to the inhibitory neurons in the cortex.

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<![CDATA[Low-rate firing limit for neurons with axon, soma and dendrites driven by spatially distributed stochastic synapses]]> https://www.researchpad.co/article/elastic_article_13830 Neurons are extended cells with multiple branching dendrites, a cell body and an axon. In an active neuronal network, neurons receive vast numbers of incoming synaptic pulses throughout their dendrites and cell body that each exhibit significant variability in amplitude and arrival time. The resulting synaptic input causes voltage fluctuations throughout their structure that evolve in space and time. The dynamics of how these signals are integrated and how they ultimately trigger outgoing spikes have been modelled extensively since the late 1960s. However, until relatively recently the majority of the mathematical formulae describing how fluctuating synaptic drive triggers action potentials have been applicable only for small neurons with the dendritic and axonal structure ignored. This has been largely due to the mathematical complexity of including the effects of spatially distributed synaptic input. Here we show that in a physiologically relevant, low-firing-rate regime, an approximate level-crossing approach can be used to provide an estimate for the neuronal firing rate even when the dendrites and axons are included. We illustrate this approach using basic neuronal morphologies that capture the fundamentals of neuronal structure. Though the models are simple, these preliminary results show that it is possible to obtain useful formulae that capture the effects of spatially distributed synaptic drive. The generality of these results suggests they will provide a mathematical framework for future studies that might require the structure of neurons to be taken into account, such as the effect of electrical fields or multiple synaptic input streams that target distinct spatial domains of cortical pyramidal cells.

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<![CDATA[Aging-associated sinus arrest and sick sinus syndrome in adult zebrafish]]> https://www.researchpad.co/article/elastic_article_13853 Because of its powerful genetics, the adult zebrafish has been increasingly used for studying cardiovascular diseases. Considering its heart rate of ~100 beats per minute at ambient temperature, which is very close to human, we assessed the use of this vertebrate animal for modeling heart rhythm disorders such as sinus arrest (SA) and sick sinus syndrome (SSS). We firstly optimized a protocol to measure electrocardiogram in adult zebrafish. We determined the location of the probes, implemented an open-chest microsurgery procedure, measured the effects of temperature, and determined appropriate anesthesia dose and time. We then proposed an PP interval of more than 1.5 seconds as an arbitrary criterion to define an SA episode in an adult fish at ambient temperature, based on comparison between the current definition of an SA episode in humans and our studies of candidate SA episodes in aged wild-type fish and Tg(SCN5A-D1275N) fish (a fish model for inherited SSS). With this criterion, a subpopulation of about 5% wild-type fish can be considered to have SA episodes, and this percentage significantly increases to about 25% in 3-year-old fish. In response to atropine, this subpopulation has both common SSS phenotypic traits that are shared with the Tg(SCN5A-D1275N) model, such as bradycardia; and unique SSS phenotypic traits, such as increased QRS/P ratio and chronotropic incompetence. In summary, this study defined baseline SA and SSS in adult zebrafish and underscored use of the zebrafish as an alternative model to study aging-associated SSS.

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<![CDATA[Novel coronavirus 19 (COVID-19) associated sinus node dysfunction: a case series]]> https://www.researchpad.co/article/elastic_article_12439 Novel coronavirus-19 disease (COVID-19) is associated with significant cardiovascular morbidity and mortality. To date, there have not been reports of sinus node dysfunction (SND) associated with COVID-19. This case series describes clinical characteristics, potential mechanisms, and short-term outcomes of COVID-19 patients who experience de novo SND.Case summaryWe present two cases of new-onset SND in patients recently diagnosed with COVID-19. Patient 1 is a 70-year-old female with no major past medical history who was intubated for acute hypoxic respiratory failure secondary to COVID-19 pneumonia and developed new-onset sinus bradycardia without a compensatory increase in heart rate in response to relative hypotension. Patient 2 is an 81-year-old male with a past medical history of an ascending aortic aneurysm, hypertension, and obstructive sleep apnoea who required intubation for COVID-19-induced acute hypoxic respiratory failure and exhibited new-onset sinus bradycardia followed by numerous episodes of haemodynamically significant accelerated idioventricular rhythm. Two weeks following the onset of SND, both patients remain in sinus bradycardia.DiscussionCOVID-19-associated SND has not previously been described. The potential mechanisms for SND in patients with COVID-19 include myocardial inflammation or direct viral infiltration. Patients diagnosed with COVID-19 should be monitored closely for the development of bradyarrhythmia and haemodynamic instability. ]]> <![CDATA[Genetic algorithm-based personalized models of human cardiac action potential]]> https://www.researchpad.co/article/elastic_article_7669 We present a novel modification of genetic algorithm (GA) which determines personalized parameters of cardiomyocyte electrophysiology model based on set of experimental human action potential (AP) recorded at different heart rates. In order to find the steady state solution, the optimized algorithm performs simultaneous search in the parametric and slow variables spaces. We demonstrate that several GA modifications are required for effective convergence. Firstly, we used Cauchy mutation along a random direction in the parametric space. Secondly, relatively large number of elite organisms (6–10% of the population passed on to new generation) was required for effective convergence. Test runs with synthetic AP as input data indicate that algorithm error is low for high amplitude ionic currents (1.6±1.6% for IKr, 3.2±3.5% for IK1, 3.9±3.5% for INa, 8.2±6.3% for ICaL). Experimental signal-to-noise ratio above 28 dB was required for high quality GA performance. GA was validated against optical mapping recordings of human ventricular AP and mRNA expression profile of donor hearts. In particular, GA output parameters were rescaled proportionally to mRNA levels ratio between patients. We have demonstrated that mRNA-based models predict the AP waveform dependence on heart rate with high precision. The latter also provides a novel technique of model personalization that makes it possible to map gene expression profile to cardiac function.

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<![CDATA[An electrodiffusive, ion conserving Pinsky-Rinzel model with homeostatic mechanisms]]> https://www.researchpad.co/article/elastic_article_7780 Neurons generate their electrical signals by letting ions pass through their membranes. Despite this fact, most models of neurons apply the simplifying assumption that ion concentrations remain effectively constant during neural activity. This assumption is often quite good, as neurons contain a set of homeostatic mechanisms that make sure that ion concentrations vary quite little under normal circumstances. However, under some conditions, these mechanisms can fail, and ion concentrations can vary quite dramatically. Standard models are thus not able to simulate such conditions. Here, we present what to our knowledge is the first multicompartmental neuron model that accounts for ion concentration variations in a way that ensures complete and consistent ion concentration and charge conservation. In this work, we use the model to explore under which activity conditions the ion concentration variations become important for predicting the neurodynamics. We expect the model to be of great value for the field of neuroscience, as it can be used to simulate a range of pathological conditions, such as spreading depression or epilepsy, which are associated with large changes in extracellular ion concentrations.

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<![CDATA[Model based estimation of QT intervals in non-invasive fetal ECG signals]]> https://www.researchpad.co/article/elastic_article_7659 The end timing of T waves in fetal electrocardiogram (fECG) is important for the evaluation of ST and QT intervals which are vital markers to assess cardiac repolarization patterns. Monitoring malignant fetal arrhythmias in utero is fundamental to care in congenital heart anomalies preventing perinatal death. Currently, reliable detection of end of T waves is possible only by using fetal scalp ECG (fsECG) and fetal magnetocardiography (fMCG). fMCG is expensive and less accessible and fsECG is an invasive technique available only during intrapartum period. Another safer and affordable alternative is the non-invasive fECG (nfECG) which can provide similar assessment provided by fsECG and fMECG but with less accuracy (not beat by beat). Detection of T waves using nfECG is challenging because of their low amplitudes and high noise. In this study, a novel model-based method that estimates the end of T waves in nfECG signals is proposed. The repolarization phase has been modeled as the discharging phase of a capacitor. To test the model, fECG signals were collected from 58 pregnant women (age: (34 ± 6) years old) bearing normal and abnormal fetuses with gestational age (GA) 20-41 weeks. QT and QTc intervals have been calculated to test the level of agreement between the model-based and reference values (fsECG and Doppler Ultrasound (DUS) signals) in normal subjects. The results of the test showed high agreement between model-based and reference values (difference < 5%), which implies that the proposed model could be an alternative method to detect the end of T waves in nfECG signals.

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<![CDATA[Machine learning-based mortality prediction of patients undergoing cardiac resynchronization therapy: the SEMMELWEIS-CRT score]]> https://www.researchpad.co/article/Nfdfae2c8-4bd7-498a-a217-27426147ea00 Our aim was to develop a machine learning (ML)-based risk stratification system to predict 1-, 2-, 3-, 4-, and 5-year all-cause mortality from pre-implant parameters of patients undergoing cardiac resynchronization therapy (CRT).Methods and resultsMultiple ML models were trained on a retrospective database of 1510 patients undergoing CRT implantation to predict 1- to 5-year all-cause mortality. Thirty-three pre-implant clinical features were selected to train the models. The best performing model [SEMMELWEIS-CRT score (perSonalizEd assessMent of estiMatEd risk of mortaLity With machinE learnIng in patientS undergoing CRT implantation)], along with pre-existing scores (Seattle Heart Failure Model, VALID-CRT, EAARN, ScREEN, and CRT-score), was tested on an independent cohort of 158 patients. There were 805 (53%) deaths in the training cohort and 80 (51%) deaths in the test cohort during the 5-year follow-up period. Among the trained classifiers, random forest demonstrated the best performance. For the prediction of 1-, 2-, 3-, 4-, and 5-year mortality, the areas under the receiver operating characteristic curves of the SEMMELWEIS-CRT score were 0.768 (95% CI: 0.674–0.861; P < 0.001), 0.793 (95% CI: 0.718–0.867; P < 0.001), 0.785 (95% CI: 0.711–0.859; P < 0.001), 0.776 (95% CI: 0.703–0.849; P < 0.001), and 0.803 (95% CI: 0.733–0.872; P < 0.001), respectively. The discriminative ability of our model was superior to other evaluated scores.ConclusionThe SEMMELWEIS-CRT score (available at semmelweiscrtscore.com) exhibited good discriminative capabilities for the prediction of all-cause death in CRT patients and outperformed the already existing risk scores. By capturing the non-linear association of predictors, the utilization of ML approaches may facilitate optimal candidate selection and prognostication of patients undergoing CRT implantation. ]]> <![CDATA[Influence of the tubular network on the characteristics of calcium transients in cardiac myocytes]]> https://www.researchpad.co/article/N7f446290-780e-4486-a1de-95187c6060a1

Transverse and axial tubules (TATS) are an essential ingredient of the excitation-contraction machinery that allow the effective coupling of L-type Calcium Channels (LCC) and ryanodine receptors (RyR2). They form a regular network in ventricular cells, while their presence in atrial myocytes is variable regionally and among animal species We have studied the effect of variations in the TAT network using a bidomain computational model of an atrial myocyte with variable density of tubules. At each z-line the t-tubule length is obtained from an exponential distribution, with a given mean penetration length. This gives rise to a distribution of t-tubules in the cell that is characterized by the fractional area (F.A.) occupied by the t-tubules. To obtain consistent results, we average over different realizations of the same mean penetration length. To this, in some simulations we add the effect of a network of axial tubules. Then we study global properties of calcium signaling, as well as regional heterogeneities and local properties of sparks and RyR2 openings. In agreement with recent experiments in detubulated ventricular and atrial cells, we find that detubulation reduces the calcium transient and synchronization in release. However, it does not affect sarcoplasmic reticulum (SR) load, so the decrease in SR calcium release is due to regional differences in Ca2+ release, that is restricted to the cell periphery in detubulated cells. Despite the decrease in release, the release gain is larger in detubulated cells, due to recruitment of orphaned RyR2s, i.e, those that are not confronting a cluster of LCCs. This probably provides a safeguard mechanism, allowing physiological values to be maintained upon small changes in the t-tubule density. Finally, we do not find any relevant change in spark properties between tubulated and detubulated cells, suggesting that the differences found in experiments could be due to differential properties of the RyR2s in the membrane and in the t-tubules, not incorporated in the present model. This work will help understand the effect of detubulation, that has been shown to occur in disease conditions such as heart failure (HF) in ventricular cells, or atrial fibrillation (AF) in atrial cells.

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<![CDATA[Disruption of genes associated with Charcot-Marie-Tooth type 2 lead to common behavioural, cellular and molecular defects in Caenorhabditis elegans]]> https://www.researchpad.co/article/N5d50b5cf-e057-490e-9c44-60569e9f28d4

Charcot-Marie-Tooth (CMT) disease is an inherited peripheral motor and sensory neuropathy. The disease is divided into demyelinating (CMT1) and axonal (CMT2) neuropathies, and although we have gained molecular information into the details of CMT1 pathology, much less is known about CMT2. Due to its clinical and genetic heterogeneity, coupled with a lack of animal models, common underlying mechanisms remain elusive. In order to gain an understanding of the normal function of genes associated with CMT2, and to draw direct comparisons between them, we have studied the behavioural, cellular and molecular consequences of mutating nine different genes in the nematode Caenorhabditis elegans (lin-41/TRIM2, dyn-1/DNM2, unc-116/KIF5A, fzo-1/MFN2, osm-9/TRPV4, cua-1/ATP7A, hsp-25/HSPB1, hint-1/HINT1, nep-2/MME). We show that C. elegans defective for these genes display debilitated movement in crawling and swimming assays. Severe morphological defects in cholinergic motors neurons are also evident in two of the mutants (dyn-1 and unc-116). Furthermore, we establish methods for quantifying muscle morphology and use these to demonstrate that loss of muscle structure occurs in the majority of mutants studied. Finally, using electrophysiological recordings of neuromuscular junction (NMJ) activity, we uncover reductions in spontaneous postsynaptic current frequency in lin-41, dyn-1, unc-116 and fzo-1 mutants. By comparing the consequences of mutating numerous CMT2-related genes, this study reveals common deficits in muscle structure and function, as well as NMJ signalling when these genes are disrupted.

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<![CDATA[Fatal heart block from intentional yew tree (Taxus baccata) ingestion: a case report]]> https://www.researchpad.co/article/Na92a0bc8-ec2f-4903-990e-8247d5560c6d

Abstract

Background 

Taxus baccata, also known as English yew, is a poison that causes cardiac arrhythmias and can result in death from cardiogenic shock.

Case summary 

A 49-year-old gentleman was admitted following yew ingestion with suicidal intent. He was bradycardic at 30 b.p.m. and hypotensive on arrival. Electrocardiography revealed complete heart block with broad complex ventricular escape rate of 30 b.p.m. Bedside echocardiography revealed severe global impairment of right and left ventricular systolic function. Urgent temporary transvenous pacing was instituted, and the patient was considered for veno-arterial extracorporeal membrane oxygenation. Unfortunately, he deteriorated rapidly and cardiorespiratory arrest ensued, and despite prolonged in-hospital resuscitation, the patient died. Post-mortem examination revealed small needle-shaped plant leaves together with seeds found in the stomach. Ante mortem serum sample analysis sent to the Royal Botanical Gardens and revealed the presence of taxine Type B alkaloids in the patient’s blood.

Discussion 

Yew poisoning is a rare occurrence, and there is currently no effective antidote. Treatment involves supportive management, comprising prolonged effective cardiopulmonary resuscitation, pacing, and mechanical cardiac support. This case illustrates the importance of prompt recognition of yew poisoning, alongside early consideration of pacing and mechanical cardiac support. Due to the rarity of this cause of heart block, and since patients may not always volunteer a history of yew ingestion, yew poisoning is something that physicians should be aware of and this should be considered in the differential diagnosis in patients with unexpected heart block. Serum analysis for taxine alkaloids can be used to confirm the diagnosis.

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<![CDATA[False-positive ST-segment elevation]]> https://www.researchpad.co/article/N846ed87f-8e16-43bb-ac8c-d394dc7010e7 ]]> <![CDATA[A case report of arrhythmogenic ventricular cardiomyopathy presenting with sustained ventricular tachycardia arising from the right and the left ventricles before structural changes are documented]]> https://www.researchpad.co/article/N96757243-c3a8-482e-9dec-db0334209365

Abstract

Background

Arrhythmogenic ventricular cardiomyopathy (AC) is a genetic progressive disease characterized by fibro-fatty replacement of either ventricles in isolation or in combination. Arrhythmogenic ventricular cardiomyopathy is frequently associated with ventricular tachycardia (VT) having a left bundle branch block (LBBB) morphology and much more rarely with VT having right bundle branch block (RBBB) morphology even when the left ventricle is involved. Cardiac magnetic resonance (CMR) imaging plays a key role in the diagnosis of AC. Sustained VT in AC may occur in the concealed stage of the disease before the manifestation of morphological abnormalities on echocardiogram; however, they almost always are accompanied by structural abnormalities of the ventricles on CMR.

Case summary

A 54-year-old man presented with sustained VT of LBBB configuration consistent with the diagnosis of AC but with no right ventricular (RV) anomalies at repeat CMR. Ten years later, he developed sustained VT with RBBB morphology and structural changes at CMR compatible with RV involvement in the setting of AC. Two years later, he suffered from recurrent identical sustained RBBB-VT with typical CMR signs of left ventricular involvement. Genetic analysis was negative for any known mutation.

Discussion

In the present report, we describe a patient with AC who first exhibited LBBB- and 10 years later RBBB-sustained VT. Contrasting with what is usually observed in patients with AC, documentations of the VT’s arising from either ventricle were found to precede the structural anomalies in the respective cardiac chambers. This case highlights that normal CMR does not exclude underlying AC contrary to the perceptions of many clinicians. In addition, it strongly encourages repeating CMR after 1–2 years when the diagnosis of AC is highly suspected.

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<![CDATA[Game changer? A sporting indication to implant a left atrial appendage closure device in a rugby player with atrial fibrillation: a case report]]> https://www.researchpad.co/article/Nf2cd79d6-2340-49a1-9b6c-1fa564661d51

Abstract

Background

Caring for athletes with cardiac disease requires an approach that caters to the specific needs of the athlete.

Case summary

A 27-year-old professional rugby player was admitted with decompensated heart failure and atrial fibrillation (AF). Transthoracic echocardiogram showed features in keeping with a dilated cardiomyopathy with severe left ventricular (LV) systolic impairment. He made good progress on evidence-based heart failure medication and his LV systolic function returned to normal. He failed to maintain sinus rhythm with cardioversion and remained in persistent AF. He then suffered a transient ischaemic attack despite appropriate anticoagulation. At 1-year follow-up, he was asymptomatic and against medical advice continued to play competitive rugby whilst taking rivaroxaban. He subsequently underwent implantation with a percutaneous left atrial appendage occlusion device, allowing him to discontinue anticoagulation, reduce his bleeding risk and resume his career, whilst simultaneously lowering the thromboembolic risk.

Discussion

Counselling should include different management options aimed at minimizing the risks to athletes if they to return to competitive sports. Left atrial appendage occlusion devices are a suitable AF-related stroke prevention strategy in athletes competing in full-contact sports.

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<![CDATA[The impact of body posture on intrinsic brain activity: The role of beta power at rest]]> https://www.researchpad.co/article/N65f7a4e6-ac5f-46ef-91d2-3d4de84bb5d0

Tying the hands behind the back has detrimental effects on sensorimotor perceptual tasks. Here we provide evidence that beta band oscillatory activity in a resting state condition might play a crucial role in such detrimental effects. EEG activity at rest was measured from thirty young participants (mean age = 24.03) in two different body posture conditions. In one condition participants were required to keep their hands freely resting on the table. In the other condition, participants’ hands were tied behind their back. Increased beta power was observed in the left inferior frontal gyrus during the tied hands condition compared to the free hands condition. A control experiment ruled out alternative explanations for observed change in beta power, including muscle tension. Our findings provide new insights on how body postural manipulations impact on perceptual tasks and brain activity.

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<![CDATA[Polymer-fiber-coupled field-effect sensors for label-free deep brain recordings]]> https://www.researchpad.co/article/N12f161cb-ce31-436b-989e-fa44b0a6dffa

Electrical recording permits direct readout of neural activity but offers limited ability to correlate it to the network topography. On the other hand, optical imaging reveals the architecture of neural circuits, but relies on bulky optics and fluorescent reporters whose signals are attenuated by the brain tissue. Here we introduce implantable devices to record brain activities based on the field effect, which can be further extended with capability of label-free electrophysiological mapping. Such devices reply on light-addressable potentiometric sensors (LAPS) coupled to polymer fibers with integrated electrodes and optical waveguide bundles. The LAPS utilizes the field effect to convert electrophysiological activity into regional carrier redistribution, and the neural activity is read out in a spatially resolved manner as a photocurrent induced by a modulated light beam. Spatially resolved photocurrent recordings were achieved by illuminating different pixels within the fiber bundles. These devices were applied to record local field potentials in the mouse hippocampus. In conjunction with the raster-scanning via the single modulated beam, this technology may enable fast label-free imaging of neural activity in deep brain regions.

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<![CDATA[Activity-dependent switches between dynamic regimes of extracellular matrix expression]]> https://www.researchpad.co/article/Ndfacbadd-d1b4-4759-ab64-7c15dc34928b

Experimental studies highlight the important role of the extracellular matrix (ECM) in the regulation of neuronal excitability and synaptic connectivity in the nervous system. In its turn, the neural ECM is formed in an activity-dependent manner. Its maturation closes the so-called critical period of neural development, stabilizing the efficient configurations of neural networks in the brain. ECM is locally remodeled by proteases secreted and activated in an activity-dependent manner into the extracellular space and this process is important for physiological synaptic plasticity. We ask if ECM remodeling may be exaggerated under pathological conditions and enable activity-dependent switches between different regimes of ECM expression. We consider an analytical model based on known mechanisms of interaction between neuronal activity and expression of ECM, ECM receptors and ECM degrading proteases. We demonstrate that either inhibitory or excitatory influence of ECM on neuronal activity may lead to the bistability of ECM expression, so two stable stationary states are observed. Noteworthy, only in the case when ECM has predominant inhibitory influence on neurons, the bistability is dependent on the activity of proteases. Excitatory ECM-neuron feedback influences may also result in spontaneous oscillations of ECM expression, which may coexist with a stable stationary state. Thus, ECM-neuronal interactions support switches between distinct dynamic regimes of ECM expression, possibly representing transitions into disease states associated with remodeling of brain ECM.

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<![CDATA[CHA 2 DS 2 ‐VASc Score and the Risk of Ventricular Tachyarrhythmic Events and Mortality in MADIT‐CRT]]> https://www.researchpad.co/article/N9ba715bc-b571-457b-be63-dbbb4e68244c

Background

We hypothesized that multiple cardiovascular comorbidities, incorporated in the CHA 2 DS 2VASc score, may be useful in the assessment of ventricular tachyarrhythmias (VTAs) and mortality risk in heart failure (HF) patients.

Methods and Results

We evaluated the association between the CHA 2 DS 2VASc score (dichotomized as high at the upper quartile [≥5] and further assessed as a continuous measure) and the risk of VTA and death among 1804 patients enrolled in MADIT‐CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy). A high CHA 2 DS 2VASc score (n=464; 26%) was inversely associated with the risk of any VTA (hazard ratio [HR]: 0.64; P=0.001), fast VTA >200 beats/min (HR; 0.51; P<0.001), and appropriate implantable cardioverter‐defibrillator shocks (HR: 0.60; P<0.001). In contrast, a high score was directly correlated with mortality risk (HR: 1.92; P<0.001) and the risk of HF or death (HR: 1.60; P<0.001). Consistently, each 1‐U increment in CHA 2 DS 2VASc was associated with a significant 13% (P=0.003) reduction in VTA risk but a corresponding 33% (P<0.001) increase in mortality risk. Patients with a high CHA 2 DS 2VASc score and left bundle‐branch block derived a pronounced 53% (P<0.001) reduction in the risk of HF or death with cardiac resynchronization therapy with defibrillator versus implantable cardioverter‐defibrillator–only therapy.

Conclusions

Our findings suggest that a high CHA 2 DS 2VASc score can be used to identify patients with mild HF who have low VTA risk and high morbidity or mortality risk and may derive a pronounced clinical benefit from cardiac resynchronization therapy without a defibrillator. These data suggest a possible role for the CHA 2 DS 2VASc score in device selection among candidates for biventricular pacing.

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<![CDATA[Renal Hydrogen Peroxide Production Prevents Salt‐Sensitive Hypertension]]> https://www.researchpad.co/article/N08cd4be9-1efd-4f72-b08a-95eb7cad4f97

Background

The regulation of sodium excretion is important in the pathogenesis of hypertension and salt sensitivity is predictive of cardiovascular events and mortality. C57Bl/6 and BALB/c mice have different blood pressure sensitivities to salt intake. High salt intake increases blood pressure in some C57Bl/6J mouse strains but not in any BALB/c mouse strain.

Methods and Results

We determined the cause of the difference in salt sensitivity between C57Bl/6 and BALB/c mice. Basal levels of superoxide and H2O2 were higher in renal proximal tubule cells (RPTCs) from BALB/c than C57Bl/6J mice. High salt diet increased H2O2 production in kidneys from BALB/c but C57Bl/6J mice. High sodium concentration (170 mmol/L) in the incubation medium increased H2O2 levels in BALB/c‐RPTCs but not in C57Bl/6J‐RPTCs. H2O2 (10 μmol/L) treatment decreased sodium transport in RPTCs from BALB/c but not C57Bl/6J mice. Overexpression of catalase in the mouse kidney predisposed BALB/c mice to salt‐sensitive hypertension.

Conclusions

Our data show that the level of salt‐induced H2O2 production negatively regulates RPTC sodium transport and determines the state of salt sensitivity in 2 strains of mice. High concentrations of antioxidants could prevent H2O2 production in renal proximal tubules, which would result in sodium retention and increased blood pressure.

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