BACKGROUND—Action potential duration (APD) variation is an important determinant of wave break and reentry. The determinants of APD variability during early ventricular fibrillation (VF) in myopathic ...human hearts have not been studied. The objective of this study was to study the role of APD restitution and short-term cardiac memory on variation in human VF.
METHODS AND RESULTS—The study consisted of 7 patients (67±9 years old) with ejection fraction <35%. Monophasic action potentials were recorded from the right and/or left ventricular septum during VF. APD60/90 was measured in sinus beat preceding induction of VF, and its amplitude was used to define 60%/90% repolarization in VF. The monophasic action potential upstroke (dV/dtmax) was used to characterize local excitability. Simple linear regression showed that variability in APDn60 was determined by APD/diastolic interval restitution (R=0.48, P<0.0001) and short-term memory (APD60 n−1, n−2, n−3, n−4; R=0.55, 0.40, 0.33, and 0.27 respectively; P<0.001). Using multiple stepwise regression, short-term memory and restitution accounted for 62% of variance in APD60 (P<0.001). Individually, memory effect had the greatest contribution to APD variability (R=0.55, P<0.0001).
CONCLUSIONS—In early human VF, short-term memory and APD/diastolic interval restitution explain most of the APD variability, with memory effects predominating. This suggests that in early human VF, short-term cardiac memory may provide a novel therapeutic target to modulate progression of VF in myopathic patients.
Abstract only Background: Cell therapy and cell derived extracellular vesicles (EVs) are promising treatment options for ischemic cardiomyopathy. Despite this increasing interest, the isolation of ...EVs is not standardized. The purpose of this study was to compare two most common methods of EV isolation, ultracentrifugation (UC) and polyethylene glycol precipitation (PEG); and also to test the hypothesis that PEG precipitation followed by UC (PEG+UC) offers a more efficient method of EV isolation compared to PEG precipitation or UC alone. Methods: EVs were isolated from mouse cardiac mesenchymal cells by either PEG, UC (2 cycles at 100,000g, 1 hour each), or PEG+UC (100,000g for 1 hour). Size analysis, protein content measurements and western blots (WB) were performed. Results: PEG precipitation yielded three distinct population of particles (~20-60nm, ~90-500nm & >1000nm – Figure 1A). UC and PEG+UC provided one distinct population of EVs (90-500nm). With PEG precipitation, the highest concentration of particles obtained were in the range of 20-60nm (~99%, Figure 1B). With PEG+UC, these smaller particles were cleared yielding an uncontaminated EV population (90-500nm). PEG precipitation yielded highest content of protein followed by PEG+UC (Figure 1C). WB demonstrated weak expression of EV markers with PEG precipitation and enriched markers with UC & PEG+UC (Figure 1D). Conclusion: PEG precipitation yields least pure population of EVs with highest protein contamination, likely from precipitation of soluble proteins. UC provides pure EV population with low yield. PEG precipitation followed by UC provides the highest yield of EVs while maintaining EV purity.
Rationale: Ventricular fibrillation (VF) leads to global ischemia. The modulation of ischemia-dependent pathways may alter the electrophysiological evolution of VF. Objective: We addressed the ...hypotheses that there is regional disease-related expression of K ATP channels in human cardiomyopathic hearts and that K ATP channel blockade promotes spontaneous VF termination by attenuating spatiotemporal dispersion of refractoriness. Methods and Results: In a human Langendorff model, electric mapping of 6 control and 9 treatment (10 μmol/L glibenclamide) isolated cardiomyopathic hearts was performed. Spontaneous defibrillation was studied and mean VF cycle length was compared regionally at VF onset and after 180 seconds between control and treatment groups. K ATP subunit gene expression was compared between LV endocardium versus epicardium in myopathic hearts. Spontaneous VF termination occurred in 1 of 6 control hearts and 7 of 8 glibenclamide-treated hearts ( P =0.026). After 180 seconds of ischemia, a transmural dispersion in VF cycle length was observed between epicardium and endocardium ( P =0.001), which was attenuated by glibenclamide. There was greater gene expression of all K ATP subunit on the endocardium compared with the epicardium ( P <0.02). In an ischemic rat heart model, transmural dispersion of refractoriness (ΔERP Transmural =ERP Epicardium −ERP Endocardium ) was verified with pacing protocols. ΔERP Transmural in control was 5±2 ms and increased to 36±5 ms with ischemia. This effect was greatly attenuated by glibenclamide (ΔERP Transmural for glibenclamide+ischemia=4.9±4 ms, P =0.019 versus control ischemia). Conclusions: K ATP channel subunit gene expression is heterogeneously altered in the cardiomyopathic human heart. Blockade of K ATP channels promotes spontaneous defibrillation in cardiomyopathic human hearts by attenuating the ischemia-dependent spatiotemporal heterogeneity of refractoriness during early VF.
Abstract only The aim of this study was to evaluate the impacts of mesenchymal stem cell (MSC) transplantation on electrophysiological remodelling following myocardial infarction (MI). Methods: Three ...weeks after coronary ligation, 3×10 6 MSCs, or culture medium alone, were directly injected into infarcted Lewis rat hearts. Hearts were excised one to two weeks later, Langendorff-perfused, optically mapped using the potentiometric dye di-4-ANEPPS, and then fixed and sectioned for morphometric and histological analyses. Gene expression was assessed by qRT-PCR. Results: Optical mapping showed that MSC transplantation attenuated the reduction in conduction velocity (CV) and the prolongation of effective refractory period (ERP) in infarcted hearts. These electrophysiological changes correlated with higher vascular density and better-preserved ventricular wall thickness in MSC-treated hearts. A number of ion channel genes showed post-MI changes in expression. In particular, the expression of Kir2.1, which mediates the inward rectifier K + current I K1 , was reduced in MI and partially restored with MSC transplantation. Conclusion: Apart from well-documented benefits such as promoting angiogenesis and limiting adverse structural remodelling, MSC transplantation improves conduction and reduces refractoriness in infarcted hearts. MSCs also partially restore Kir2.1 expression, which would enhance I K1 and contribute to a more negative resting membrane potential, allowing for more Na + channels to open during depolarization and improving CV. As I K1 contributes to repolarization, restoring Kir2.1 expression would also attenuate ERP prolongation. Our experiments showed that MSCs have the capacity to alter cardiac ion channel expression and mitigate adverse electrophysiological remodelling following MI. Thus MSC transplantation may be a potential strategy to prevent post-MI arrhythmias.
Background: Modulation of ischemia-dependent pathways alters electrophysiological evolution of ventricular fibrillation (VF). Hypothesis: 1) There is regional disease-related expression of ...KATP-channels in human cardiomyopathic hearts. 2) KATP- channel blockade promotes spontaneous VF termination by attenuating spatiotemporal dispersion of refractoriness (ΔERP). Methods and Results: Electric mapping of control (n=6) and treatment (n=9, 10 ?mol/L glibenclamide) isolated human cardiomyopathic hearts was performed. Spontaneous defibrillation and KATP-subunit gene expression were studied. Spontaneous VF termination occurred in 1/6 control and 7/8 treated hearts (p=0.026). After 180 seconds of ischemia, LV transmural dispersion in VF cycle length was observed (p=0.001), which was attenuated by glibenclamide. There was greater gene expression of all KATP--subunit on the endocardium compared with the epicardium (p<0.02). In ischemic rat heart model, ΔERP was verified with pacing protocols (365ms vs 4.94ms, p=0.019). Conclusions: KATP channel subunit gene expression is heterogeneously altered in the cardiomyopathic human heart. Blockade of KATP channels promotes spontaneous defibrillation by attenuating ischemia-dependent ΔERP during VF. Key Words: Potassium Channels, Ventricular Fibrillation, Arrhythmia, Glibenclamide.
Efficacy of noncontact mapping in detecting epicardial activation Shokrollahi, E.; Krishnan, S.; Masse, S. ...
2009 Annual International Conference of the IEEE Engineering in Medicine and Biology Society,
01/2009, Letnik:
2009
Conference Proceeding, Journal Article
The aim of this study is to determine if some of the characteristics of reconstructed unipolar electrograms from the noncontact mapping system can be used to detect epicardial electrical activation ...in a canine heart. This would help the electrophysiologist know where exactly the origin or the critical point in tissue is located. Following this, arrhythmia can be successfully treated by ablating that part of the tissue of heart. Virtual electrograms were recorded while pacing the right ventricle of an open-chest dog at multiple endocardial and epicardial sites using the commercially available noncontact mapping system (EnSite 3000). The endocardial and epicardial paced virtual electrograms from the juxtaposing sites allow for analyzing systematically the differences in their morphologies. Maximal dV/dt, area under the depolarization curve and latency extracted from unipolar electrograms demonstrated significant difference between epicardial and endocardial pacing sites with a p-value of less than 0.01 in all three cases. The above features were fed to a linear discriminant analysis based classifier and high classification accuracy was achieved. In conclusion, reliable criteria can be proposed to allow for discrimination of an endocardial versus epicardial origin of electrical activation.
In this article presents two techniques of commands DTC (direct torque control) and DPC (direct power control) applied in the system of converting wind energy with storage. The wind generator used is ...based on a double fed induction generator (DFIG) where the stator is linked directly with the network and the rotor is connected to the network through the power converter. The flywheel energy storage system (FESS) based on a flywheel, an induction machine (IM) and an electronic power converter is associated with the wind generator via the DC bus. The two converters side DFIG and the (FESS) are controlled by the DTC. The three-level converter side electricity grid which ensures constant DC bus voltage is controlled by the DPC, in order to mitigate the wave quality problems. In the literature, this control strategy has been frequently used for the two levels converter. The direct control of these systems has a purpose of eliminating the block of pulse width modulation and loops of regulations internal controlled variables, which gives a faster response. The use of switching table makes the system more efficient from the technical and economic view. A maximum power tracking technique «Maximum Power Point Tracking» (MPPT) and a pitch angle control strategy are presented. The model of the complete system is developed in Matlab/Simulink/to analyze from the simulation results the integration of wind chain to electric networks.
Physiological pressure measurement is one of the most common applications of sensors in healthcare. Particularly, continuous pressure monitoring provides key information for early diagnosis, ...patient-specific treatment, and preventive healthcare. This paper presents a thin-film flexible wireless pressure sensor for continuous pressure measurement in a wide range of medical applications but mainly focused on interface pressure monitoring during compression therapy to treat venous insufficiency. The sensor is based on a pressure-dependent capacitor (C) and printed inductive coil (L) that form an inductor-capacitor (LC) resonant circuit. A matched reader coil provides an excellent coupling at the fundamental resonance frequency of the sensor. Considering varying requirements of venous ulceration, two versions of the sensor, with different sizes, were finalized after design parameter optimization and fabricated using a cost-effective and simple etching method. A test setup consisting of a glass pressure chamber and a vacuum pump was developed to test and characterize the response of the sensors. Both sensors were tested for a narrow range (0-100 mmHg) and a wide range (0-300 mmHg) to cover most of the physiological pressure measurement applications. Both sensors showed good linearity with high sensitivity in the lower pressure range <100 mmHg, providing a wireless monitoring platform for compression therapy in venous ulceration.
Rapid detection and phenotyping of pathogenic microbes is critical for administration of effective antibiotic therapies and for impeding the spread of antibiotic resistance. Here, we present a novel ...platform, rapid ultrasensitive detector (RUSD), that utilizes the high reflectance coefficient at high incidence angles when light travels from low- to high-refractive-index media. RUSD leverages a principle that does not require complex manufacturing, labeling, or processing steps. Utilizing RUSD, we can detect extremely low cell densities (optical density OD ≥ 5 × 10-7) that correspond to approximately 20 bacterial cells or a single fungal cell in the detection volume, which is nearly 4 orders of magnitude more sensitive than standard OD methods. RUSD can measure minimum inhibitory concentrations (MICs) of commonly used antibiotics against gram-negative and gram-positive bacteria, including Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli, within 2 to 4 h. Here, we demonstrate that antibiotic susceptibility tests for several pathogens can rapidly be performed with RUSD using both small inoculum sizes (500 cells/mL) and larger inoculum sizes (5 × 105 cells/mL) used in standard antibiotic susceptibility tests. We anticipate that the RUSD system will be particularly useful for the cases in which antibiotic susceptibility tests have to be done with a limited number of bacterial cells that are available. Its compatibility with standard antibiotic susceptibility tests, simplicity, and low cost can make RUSD a viable and rapidly deployed diagnostic tool.
Background
Arrhythmia‐induced cardiomyopathy (AIC) is characterized by improvement in left ventricular ejection fraction (LVEF) following arrhythmia treatment. Predictors of recovery in LVEF are not ...well understood.
Objective
We evaluated predictors of AIC recovery in a large multicenter cohort.
Methods
In total, 243 patients (age 65 ± 11, 73% male) with AIC caused by atrial fibrillation (49%), atrial tachycardia (20%), and premature ventricular contractions (PVCs; 31%) were treated and included. LVEF was assessed before and after treatment. Patients were stratified by arrhythmia duration (known KN, n = 132 vs. unknown UKN, n = 111), arrhythmia type, LVEF, and presence of structural heart disease (SHD).
Results
Arrhythmia treatment was rhythm control in 95%. Median arrhythmia duration in the KN group was 47 months (25–75th percentile, 24–80 months). Post treatment LVEF was higher in KN group (55.9 ± 7 vs. 46.2 ± 12%; p < .0001) but the degree of LVEF improvement was similar (21.2 ± 9 vs. 19.4 ± 11; p = .16). Comparing highest quartile (longest arrhythmia duration) versus the rest of the KN group, the extent of LVEF improvement was similar (21.5 ± 8 vs. 21 ± 9%; p = .1). Patients in lowest index LVEF quartile (n = 74) had more PVC‐induced AIC, greater EF improvement after treatment (24 ± 17 vs. 19 ± 7%; p < .0001) but lower post treatment EF (45 ± 14 vs. 54 ± 8%; p < .0001) versus other patients. Patients with SHD had lower index EF (28 ± 8 vs. 34 ± 8%; p < .0001) and lower final EF (47 ± 12 vs. 56 ± 7; p ≪ .0001). In multivariate regression, low index LVEF predicted myocardial recovery (odds ratio, 11.4; p < .005).
Conclusions
In this AIC cohort, LVEF improved regardless of arrhythmia duration or type but those with PVCs had lower index LVEF and had less recovery. Low index LVEF predicted LVEF recovery following arrhythmia treatment.
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