Search

Background: Cardiac optical mapping is an imaging technique that measures fluorescent signals across a cardiac preparation. Dual optical imaging of voltage-sensitive and calcium-sensitive probes allows for simultaneous recordings of cardiac action potentials and intracellular calcium transients with high spatiotemporal resolution. The analysis of these complex optical datasets is both time intensive and technically challenging; as such, we have developed a software package for semi-automated image processing and analysis. Herein, we report an updated version of our software package (KairoSight-3.0) with features to enhance the characterization of cardiac parameters using optical signals. Methods: To test software validity and applicability, we used Langendorff-perfused heart preparations to record transmembrane voltage and intracellular calcium signals from the epicardial surface. Isolated hearts from guinea pigs and rats were loaded with a potentiometric dye (RH237) and/or calcium indicator dye (Rhod-2AM) and fluorescent signals were acquired. We used Python 3.8.5 programming language to develop the KairoSight-3.0 software. Cardiac maps were validated with a user-specified manual mapping approach. Results: Manual maps of action potential duration (30 or 80 % repolarization), calcium transient duration (30 or 80 % reuptake), action potential and calcium transient alternans were constituted to validate the accuracy of software-generated maps. Manual and software maps had high accuracy, with >97 % of manual and software values falling within 10 ms of each other and >75 % within 5 ms for action potential duration and calcium transient duration measurements (n = 1000–2000 pixels). Further, our software package includes additional measurement tools to analyze signal-to-noise ratio, conduction velocity, action potential and calcium transient alternans, and action potential-calcium transient coupling time to produce physiologically meaningful optical maps. Conclusions: KairoSight-3.0 has enhanced capabilities to perform measurements of cardiac electrophysiology, calcium handling, alternans, and the excitation-contraction coupling with satisfactory accuracy.

Abstract One of the quantum theory concepts on which quantum information processing stands is superposition. Here we provide experimental evidence for the existence of classical analogues to the coherent superposition of energy states, which is made possible by the Hertz-type nonlinearity of the granules together with the external driving field. The granules’ nonlinear vibrations are projected into the linear modes of vibration, which depend on one another through the phase and form a coherent superposition. We show that the amplitudes of the coherent states form the components of a state vector that spans a two-dimensional Hilbert space, and time enables the system to span its Hilbert space parametrically. Thus, the superposition of states can be exploited in two-state quantum-like computations without decoherence and wave function collapse. Finally, we demonstrate the experimental realization of applying a reversible Hadamard gate to a pure base state that brings the state into a superposition.

Background: Adaptive cardiac resynchronization therapy (aCRT) is known to have clinical benefits over conventional CRT, but the mechanisms are unclear. Objective: Compare effects of aCRT and conventional CRT on electrical dyssynchrony. Methods: A prospective, double-blind, 1:1 parallel-group assignment randomized controlled trial in patients receiving CRT for routine clinical indications. Participants underwent cardiac computed tomography and 128-electrode body surface mapping. The primary outcome was change in electrical dyssynchrony measured on the epicardial surface using noninvasive electrocardiographic imaging before and 6 months post-CRT. Ventricular electrical uncoupling (VEU) was calculated as the difference between the mean left ventricular (LV) and right ventricular (RV) activation times. An electrical dyssynchrony index (EDI) was computed as the standard deviation of local epicardial activation times. Results: We randomized 27 participants (aged 64 ± 12 years; 34% female; 53% ischemic cardiomyopathy; LV ejection fraction 28% ± 8%; QRS duration 155 ± 21 ms; typical left bundle branch block [LBBB] in 13%) to conventional CRT (n = 15) vs aCRT (n = 12). In atypical LBBB (n = 11; 41%) with S waves in V5-V6, conduction block occurred in the anterior RV, as opposed to the interventricular groove in strict LBBB. As compared to baseline, VEU reduced post-CRT in the aCRT (median reduction 18.9 [interquartile range 4.3–29.2 ms; P = .034]), but not in the conventional CRT (21.4 [-30.0 to 49.9 ms; P = .525]) group. There were no differences in the degree of change in VEU and EDI indices between treatment groups. Conclusion: The effect of aCRT and conventional CRT on electrical dyssynchrony is largely similar, but only aCRT harmoniously reduced interventricular dyssynchrony by reducing RV uncoupling.

Electrocardiograms (ECG) are universally used to measure the electrical activity of the heart; however, variations in recording techniques and/or subject demographics can affect ECG interpretation. In this study, we investigated variables that are likely to influence ECG metric measurements in cardiovascular research, including recording technique, use of anesthesia, and animal model characteristics. Awake limb lead ECG recordings were collected in vivo from adult guinea pigs using a platform ECG system, while recordings in anesthetized animals were performed using both a platform and needle ECG system. We report significant heterogeneities in ECG metric values that are attributed to methodological differences (e.g., ECG lead configuration, ECG recording platform, presence or absence of anesthesia) that persist even within the same cohort of animals. Further, we report that variability in animal demographics is preserved in vivo ECG recordings—with animal age serving as a significant contributor, while sex-specific influences were less pronounced. Methodological approaches and subject demographics should be fully considered when interpreting ECG values in animal models, comparing datasets between studies, or developing artificial intelligence algorithms that utilize an ECG database.

Background: Sex is a well-recognized risk factor for sudden cardiac death (SCD). We hypothesized that sex modifies the association of electrophysiological (EP) substrate with SCD. Objective: The purpose of this study was to determine whether there are sex differences in electrocardiographic (ECG) measures and whether sex modifies the association of ECG measures of EP substrate with SCD. Methods: Participants from the Atherosclerosis Risk in Communities study with analyzable ECGs (n = 14,725; age 54.2 ± 5.8 years; 55% female; 74% white) were included. EP substrate was characterized by heart rate, QRS, QTc, Cornell voltage, spatial ventricular gradient (SVG), and sum absolute QRST integral (SAI QRST) ECG metrics. Two competing outcomes were adjudicated: SCD and non-SCD. Interaction of ECG metrics with sex was studied in Cox proportional hazards and Fine-Gray competing risk models. Model 1 was adjusted for prevalent cardiovascular disease (CVD) and risk factors. Time-updated model 2 was additionally adjusted for incident nonfatal CVD. Relative hazard ratio (RHR) and relative subhazard ratio with 95% confidence interval (CI) for SCD and non-SCD risk for women relative to men were calculated. Model 1 was adjusted for prevalent CVD and risk factors. Time-updated model 2 was additionally adjusted for incident nonfatal CVD. Results: Over median follow-up of 24.4 years, there were 530 SCDs (incidence 1.72; 95% CI 1.58–1.88 per 1000 person-years). Women compared to men experienced a greater risk of SCD associated with Cornell voltage (RHR 1.18; 95% CI 1.06–1.32; P = .003), SAI QRST (RHR 1.16; 95% CI 1.04–1.30; P = .007), and SVG magnitude (RHR 1.24; 95% CI 1.05–1.45; P = .009), independently from incident CVD. Conclusion: In women, the global EP substrate is associated with up to 24% greater risk of SCD than in men, suggesting differences in underlying mechanisms and the need for sex-specific SCD risk stratification.

Objectives We hypothesised that (1) the prevalent cardiovascular disease (CVD) is associated with global electrical heterogeneity (GEH) after adjustment for demographic, anthropometric, socioeconomic and traditional cardiovascular risk factors, (2) there are sex differences in GEH and (3) sex modifies an association of prevalent CVD with GEH.Design Cross-sectional, cohort study.Setting Prospective African-American The Jackson Heart Study (JHS) with a nested family cohort in 2000–2004 enrolled residents of the Jackson, Mississippi metropolitan area.Participants Participants from the JHS with analysable ECGs recorded in 2009–2013 (n=3679; 62±12 y; 36% men; 863 family units). QRS, T and spatial ventricular gradient (SVG) vectors’ magnitude and direction, spatial QRS-T angle and sum absolute QRST integral (SAI QRST) were measured.Outcome Prevalent CVD was defined as the history of (1) coronary heart disease defined as diagnosed/silent myocardial infarction, or (2) revascularisation procedure defined as prior coronary/peripheral arterial revascularisation, or (3) carotid angioplasty/carotid endarterectomy, or (4) stroke.Results In adjusted mixed linear models, women had a smaller spatial QRS-T angle (−12.2 (95% CI −19.4 to -5.1)°; p=0.001) and SAI QRST (−29.8 (−39.3 to −20.3) mV*ms; p

BackgroundMechanisms of arrhythmogenicity in hypertrophic cardiomyopathy (HCM) are not well understood.ObjectiveTo characterize an electrophysiological substrate of HCM in comparison to ischemic cardiomyopathy (ICM), or healthy individuals.MethodsWe conducted a prospective case-control study. The study enrolled HCM patients at high risk for ventricular tachyarrhythmia (VT) [n = 10; age 61 ± 9 years; left ventricular ejection fraction (LVEF) 60 ± 9%], and three comparison groups: healthy individuals (n = 10; age 28 ± 6 years; LVEF > 70%), ICM patients with LV hypertrophy (LVH) and known VT (n = 10; age 64 ± 9 years; LVEF 31 ± 15%), and ICM patients with LVH and no known VT (n = 10; age 70 ± 7 years; LVEF 46 ± 16%). All participants underwent 12-lead ECG, cardiac CT or MRI, and 128-electrode body surface mapping (BioSemi ActiveTwo, Netherlands). Non-invasive voltage and activation maps were reconstructed using the open-source SCIRun (University of Utah) inverse problem-solving environment.ResultsIn the epicardial basal anterior segment, HCM patients had the greatest ventricular activation dispersion [16.4 ± 5.5 vs. 13.1 ± 2.7 (ICM with VT) vs. 13.8 ± 4.3 (ICM no VT) vs. 8.1 ± 2.4 ms (Healthy); P = 0.0007], the largest unipolar voltage [1094 ± 211 vs. 934 ± 189 (ICM with VT) vs. 898 ± 358 (ICM no VT) vs. 842 ± 90 μV (Healthy); P = 0.023], and the greatest voltage dispersion [median (interquartile range) 215 (161–281) vs. 189 (143–208) (ICM with VT) vs. 158 (109–236) (ICM no VT) vs. 110 (106–168) μV (Healthy); P = 0.041]. Differences were also observed in other endo-and epicardial basal and apical segments.ConclusionHCM is characterized by a greater activation dispersion in basal segments, a larger voltage, and a larger voltage dispersion through LV.Clinical Trial Registrationwww.clinicaltrials.gov Unique identifier: NCT02806479.

Background Race is an established risk factor for sudden cardiac death (SCD). We sought to determine whether the association of electrophysiological substrate with SCD varies between black and white individuals. Methods and Results Participants from the ARIC (Atherosclerosis Risk in Communities) study with analyzable ECGs (n=14 408; age, 54±6 years; 74% white) were included. Electrophysiological substrate was characterized by ECG metrics. Two competing outcomes were adjudicated: SCD and non‐SCD. Interaction of ECG metrics with race was studied in Cox proportional hazards and Fine‐Gray competing risk models, adjusted for prevalent cardiovascular disease, risk factors, and incident nonfatal cardiovascular disease. At the baseline visit, adjusted for age, sex, and study center, blacks had larger spatial ventricular gradient magnitude (0.30 mV; 95% CI, 0.25–0.34 mV), sum absolute QRST integral (18.4 mV*ms; 95% CI, 13.7–23.0 mV*ms), and Cornell voltage (0.30 mV; 95% CI, 0.25–0.35 mV) than whites. Over a median follow‐up of 24.4 years, SCD incidence was higher in blacks (2.86 per 1000 person‐years; 95% CI, 2.50–3.28 per 1000 person‐years) than whites (1.37 per 1000 person‐years; 95% CI, 1.22–1.53 per 1000 person‐years). Blacks with hypertension had the highest rate of SCD: 4.26 (95% CI, 3.66–4.96) per 1000 person‐years. Race did not modify an association of ECG variables with SCD, except QRS‐T angle. Spatial QRS‐T angle was associated with SCD in whites (hazard ratio, 1.38; 95% CI, 1.25–1.53) and hypertension‐free blacks (hazard ratio, 1.52; 95% CI, 1.09–2.12), but not in blacks with hypertension (hazard ratio, 1.15; 95% CI, 0.99–1.32) (P‐interaction=0.004). Conclusions Race did not modify associations of electrophysiological substrate with SCD and non‐SCD. Electrophysiological substrate does not explain racial disparities in SCD rate.

Cannabis is one of the most commonly used illicit recreational drugs that is often taken for medicinal purposes. The psychoactive ingredient in cannabis is Δ9-Tetrahydrocannabinol (Δ9-THC, hereafter referred to as THC), which is an agonist at the endocannabinoid receptors CB1R and CB2R. Here, we exposed zebrafish embryos to THC during the gastrulation phase to determine the long-term effects during development. We specifically focused on reticulospinal neurons known as the Mauthner cells (M-cell) that are involved in escape response movements. The M- cells are born during gastrulation, thus allowing us to examine neuronal morphology of neurons born during the time of exposure. After the exposure, embryos were allowed to develop normally and were examined at two days post-fertilization for M-cell morphology and escape responses. THC treated embryos exhibited subtle alterations in M-cell axon diameter and small changes in escape response dynamics to touch. Because escape responses were altered, we also examined muscle fiber development. The fluorescent labelling of red and white muscle fibers showed that while muscles were largely intact, the fibers were slightly disorganized with subtle but significant changes in the pattern of expression of nicotinic acetylcholine receptors. However, there were no overt changes in the expression of nicotinic receptor subunit mRNA ascertained by qPCR. Embryos were allowed to further develop until 5 dpf, when they were examined for overall levels of movement. Animals exposed to THC during gastrulation exhibited reduced activity compared with vehicle controls. Together, these findings indicate that zebrafish exposed to THC during the gastrula phase exhibit small changes in neuronal and muscle morphology that may impact behavior and locomotion.

Defensins are small cysteine-rich endogenous host defense peptides expressed in all higher plants. They are thought to be important players in the defense arsenal of plants against fungal and oomycete pathogens. However, little is known regarding the antibacterial activity of these peptides. The genome of the model legume Medicago truncatula contains 63 genes each encoding a defensin with a tetradisulfide array. A unique bi-domain defensin, designated MtDef5, was recently characterized for its potent broad-spectrum antifungal activity. This 107-amino acid defensin contains two domains, 50 amino acids each, linked by a short peptide APKKVEP. Here, we characterize antibacterial activity of this defensin and its two domains, MtDef5A and MtDef5B, against two economically important plant bacterial pathogens, Gram-negative Xanthomonas campestris and Gram-positive Clavibacter michiganensis. MtDef5 inhibits the growth of X. campestris, but not C. michiganensis, at micromolar concentrations. MtDef5B, but not MtDef5A, exhibits more potent antibacterial activity than its parent MtDef5. MtDef5 and each of its two domains induce distinct morphological changes and cell death in X. campestris. They permeabilize the bacterial plasma membrane and translocate across membranes to the cytoplasm. They bind to negatively charged DNA indicating these peptides may kill bacterial cells by inhibiting DNA synthesis and/or transcription. The cationic amino acids present in the two γ-core motifs of MtDef5 that were previously shown to be important for its antifungal activity are also important for its antibacterial activity. MtDef5 and its more potent single domain MtDef5B have the potential to be deployed as antibacterial agents for control of a Xanthomonas wilt disease in transgenic crops.

BackgroundIn human cardiac ventricle, IK1 is mainly comprised Kir2.1, but Kir2.2 and Kir2.3 heterotetramers occur and modulate IK1. Long-QT syndrome-9-associated CAV3 mutations cause decreased Kir2.1 current density, but Kir2.x heterotetramers have not been studied. Here, we determine the effect of long-QT syndrome-9-CAV3 mutation F97C on Kir2.x homo- and heterotetramers and model-associated arrhythmia mechanisms.Methods and resultsSuper-resolution microscopy, co-immunoprecipitation, cellular electrophysiology, on-cell Western blotting, and simulation of Purkinje and ventricular myocyte mathematical models were used. Kir2.x isoforms have unique subcellular colocalization in human cardiomyocytes and coimmunoprecipitate with Cav3. F97C-Cav3 decreased peak inward Kir2.2 current density by 50% (-120 mV; P=0.019) and peak outward by 75% (-40 mV; P

Di-2-ethylhexyl phthalate (DEHP) is commonly used in the manufacturing of plastic materials, including intravenous bags, blood storage bags, and medical-grade tubing. DEHP can leach from plastic medical products, which can result in inadvertent patient exposure. DEHP concentrations were measured in red blood cell units stored between 7 and 42 days (17–119 μg/ml). Using these concentrations as a guide, Langendorff-perfused rat heart preparations were acutely exposed to DEHP. Sinus activity remained stable with lower doses of DEHP (25–50 μg/ml), but sinus rate declined by 43% and sinus node recovery time (SNRT) prolonged by 56.5% following 30-min exposure to 100 μg/ml DEHP. DEHP exposure also exerted a negative dromotropic response, as indicated by a 69.4% longer PR interval, 108.5% longer Wenckebach cycle length (WBCL), and increased incidence of atrioventricular (AV) uncoupling (60-min exposure). Pretreatment with doxycycline partially rescued the effects of DEHP on sinus activity, but did not ameliorate the effects on AV conduction. DEHP exposure also prolonged the ventricular action potential and effective refractory period, but had no measurable effect on intracellular calcium transient duration. Follow-up studies using human-induced pluripotent stem cell-derived cardiomyocytes confirmed that DEHP slows electrical conduction in a time (15 min–3 h) and dose-dependent manner (10–100 μg/ml). Previous studies have suggested that phthalate toxicity is specifically attributed to metabolites of DEHP, including mono-2-ethylhexylphthalate. This study demonstrates that DEHP exposure also contributes to cardiac dysfunction in a dose- and time-dependent manner. Future work is warranted to investigate the impact of DEHP (and its metabolites) on human health, with special consideration for clinical procedures that employ plastic materials. [ABSTRACT FROM AUTHOR]