Prognostic Implication of Platelet Reactivity According to Left Ventricular Systolic Dysfunction Status in Patients Treated With Drug-Eluting Stent Implantation: Analysis of the PTRG-DES Consortium.

BACKGROUND: Coronary artery disease patients undergoing percutaneous coronary intervention (PCI) often exhibit reduced left ventricular ejection fraction (LVEF). However, the impact of LV dysfunction status in conjunction with platelet reactivity on clinical outcomes has not been previously investigated. METHODS: From the multicenter PTRG-DES (Platelet function and genoType-Related long-term prognosis in DES-treated patients) consortium, the patients were classified as preserved-EF (PEF: LVEF ≥ 50%) and reduced-EF (REF: LVEF< 5 0%) group by echocardiography. Platelet reactivity was measured using VerifyNow P2Y12 assay and high platelet reactivity (HPR) was defined as PRU ≥ 252. The major adverse cardiac and cerebrovascular events (MACCEs) were a composite of death, myocardial infarction, stent thrombosis and stroke at 5 years after PCI. Major bleeding was defined as Bleeding Academic Research Consortium bleeding types 3-5. RESULTS: A total of 13,160 patients from PTRG-DES, 9,319 (79.6%) patients with the results of both PRU and LVEF were analyzed. The incidence of MACCE and major bleeding was higher in REF group as compared with PEF group (MACCEs: hazard ratio [HR] 2.17, P < 0.001, 95% confidence interval [CI] 1.85-2.55; major bleeding: HR 1.78, P < 0.001, 95% CI 1.39-2.78). The highest rate of MACCEs was found in patients with REF and HPR, and the difference between the groups was statistically significant (HR 3.14 in REF(+)/HPR(+) vs. PEF(+)/HPR(-) group, P < 0.01, 95% CI 2.51-3.91). The frequency of major bleeding was not associated with the HPR in either group. CONCLUSION: LV dysfunction was associated with an increased incidence of MACCEs and major bleeding in patients who underwent PCI. The HPR status further exhibited significant increase of MACCEs in patients with LV dysfunction in a large, real-world registry. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04734028.

In Situ Confocal Fluorescence Lifetime Imaging of Nanopore Electrode Arrays with Redox Active Fluorogenic Amplex Red.

Direct imaging of electrochemical processes on electrode surfaces is a central part of understanding spatially heterogeneous electrochemical processes on the surfaces. Herein, we report a strategy for the spatially resolved imaging of local faradaic processes on nanoscale electrochemical interfaces. This strategy is based on fluorescence lifetime imaging microscopy (FLIM) with the use of Amplex Red as a fluorogenic redox probe. After verifying the capability of Amplex Red for fluorescence lifetime imaging, we demonstrated the turn-on FLIM-based imaging of faradaic processes on the electrochemical interfaces of different dimensions. In particular, we achieved spatially resolved visualization of the local electrochemical processes occurring on even nanopore electrode arrays as well as conventional microelectrodes, including disk-shaped ultramicroelectrodes and interdigitated array microelectrodes.

Electrochemical Zero-Mode Waveguide Potential-Dependent Fluorescence of Glutathione Reductase at Single-Molecule Occupancy.

Understanding functional states of individual redox enzymes is important because electron-transfer reactions are fundamental to life, and single-enzyme molecules exhibit molecule-to-molecule heterogeneity in their properties, such as catalytic activity. Zero-mode waveguides (ZMW) constitute a powerful tool for single-molecule studies, enabling investigations of binding reactions up to the micromolar range due to the ability to trap electromagnetic radiation in zeptoliter-scale observation volumes. Here, we report the potential-dependent fluorescence dynamics of single glutathione reductase (GR) molecules using a bimodal electrochemical ZMW (E-ZMW), where a single-ring electrode embedded in each of the nanopores of an E-ZMW array simultaneously serves to control electrochemical potential and to confine optical radiation within the nanopores. Here, the redox state of GR is manipulated using an external potential control of the Au electrode in the presence of a redox mediator, methyl viologen (MV). Redox-state transitions in GR are monitored by correlating electrochemical and spectroscopic signals from freely diffusing MV/GR in 60 zL effective observation volumes at single GR molecule average pore occupancy, ⟨n⟩ ∼ 0.8. Fluorescence intensities decrease (increase) at reducing (oxidizing) potentials for MV due to the MV-mediated control of the GR redox state. The spectroelectrochemical response of GR to the enzyme substrate, i.e., glutathione disulfide (GSSG), shows that GSSG promotes GR oxidation via enzymatic reduction. The capabilities of E-ZMWs to probe spectroelectrochemical phenomena in zL-scale-confined environments show great promise for the study of single-enzyme reactions and can be extended to important technological applications, such as those in molecular diagnostics.

Role of electrochemical reactions in the degradation of formamidinium lead halide hybrid perovskite quantum dots.

Organic-inorganic hybrid perovskites are widely utilized in solar driven chemistry such as photocatalysis, hydrogen evolution, and oxygen reduction. Hybrid perovskites contain various components with high polarity and/or charge values, which undergo transformations due to ion exchange, photoinduced phase segregation, or ion migration. These variable characteristics make perovskites "soft materials". Meanwhile, optoelectronic devices often operate under electrochemical reactions in the presence of an electrical field. To examine the effect of this field on the material/photophysical properties of hybrid perovskites, hybrid FAPbBr3 (FA+: CH(NH2)2+) perovskite quantum dots (PQDs) were synthesized. In this study, we report the spectroelectrochemical investigation of the hybrid FAPbBr3 PQDs to understand the electrochemical stability and degradation process. We also found that the electrochemical condition played an important role in inducing defect-mediated oxidation/reduction reactions, changing the photophysical properties of hybrid PQDs, and causing their irreversible transformations to various lead halide plumbate complexes. These findings can help develop a strategy for enhancing the operational performance of PQDs for the solar driven chemistry.

Review of History of Basic Principles of Burn Wound Management.

Thermal energy is an essential and useful resource to humans in modern society. However, a consequence of using heat carelessly is burns. Burn injuries have various causes, such as exposure to flame, radiation, electrical, and chemical sources. In this study, we reviewed the history of burn wound care while focusing on the basic principles of burn management. Through this review, we highlight the need for careful monitoring and customization when treating burn victims at each step of wound care, as their individual needs may differ. We also propose that future research should focus on nanotechnology-based skin grafts, as this is a promising area for further improvement in wound care.

Single Entity Electrochemistry in Nanopore Electrode Arrays: Ion Transport Meets Electron Transfer in Confined Geometries.

Electrochemical measurements conducted in confined volumes provide a powerful and direct means to address scientific questions at the nexus of nanoscience, biotechnology, and chemical analysis. How are electron transfer and ion transport coupled in confined volumes and how does understanding them require moving beyond macroscopic theories? Also, how do these coupled processes impact electrochemical detection and processing? We address these questions by studying a special type of confined-volume architecture, the nanopore electrode array, or NEA, which is designed to be commensurate in size with physical scaling lengths, such as the Debye length, a concordance that offers performance characteristics not available in larger scale structures.The experiments described here depend critically on carefully constructed nanoscale architectures that can usefully control molecular transport and electrochemical reactivity. We begin by considering the experimental constraints that guide the design and fabrication of zero-dimensional nanopore arrays with multiple embedded electrodes. These zero-dimensional structures are nearly ideal for exploring how permselectivity and unscreened ion migration can be combined to amplify signals and improve selectivity by enabling highly efficient redox cycling. Our studies also highlight the benefits of arrays, in that molecules escaping from a single nanopore are efficiently captured by neighboring pores and returned to the population of active redox species being measured, benefits that arise from coupling ion accumulation and migration. These tools for manipulating redox species are well-positioned to explore single molecule and single particle electron transfer events through spectroelectrochemistry, studies which are enabled by the electrochemical zero-mode waveguide (ZMW), a special hybrid nanophotonic/nanoelectronic architecture in which the lower ring electrode of an NEA nanopore functions both as a working electrode to initiate electron transfer reactions and as the optical cladding layer of a ZMW. While the work described here is largely exploratory and fundamental, we believe that the development of NEAs will enable important applications that emerge directly from the unique coupled transport and electron-transfer capabilities of NEAs, including in situ molecular separation and detection with external stimuli, redox-based electrochemical rectification in individually encapsulated nanopores, and coupled sorters and analyzers for nanoparticles.

Characteristics and prognosis of patients with cryptogenic stroke and suggestive of patent foramen ovale.

AIMS: The purpose of this study were to identify the usefulness of screening for PFO using agitated saline echocardiography (ASE) and characteristics and prognosis of patients with suggestive of patent foramen ovale (PFO). METHODS: Three hundred three patients (mean age, 53 ± 9 years; 199 [66%] men) admitted with acute stroke or suspicion of stroke were included. Patients were classified into those with and without right-to-left shunt (RLS) according to the ASE results (positive ASE [n = 92] vs. negative ASE [n = 211]). Fifty-one out of ninety-two patients with positive ASE and twenty-one out of two hundred eleven patients with negative ASE underwent TEE with ASE to confirm PFO. RESULTS: Ninety-two were positive for ASE and thirty-six of the fifty-one patients who underwent TEE were confirmed as having PFO. Of the patients with RLS grade 1, 50% were diagnosed with PFO and all patients with RLS grade ≥ 2 were diagnosed with PFO. All patients with negative ASE had no PFO (sensitivity of 100% and specificity of 58%). Patients with positive ASE were younger, had a lower body mass, and a lower prevalence of hypertension. The positive ASE patients had a higher mean S' velocity and better diastolic function. Four of ninety-one patients with positive ASE and thirteen of one hundred seventy-seven showed recurrence of stroke and suspicion of stroke. CONCLUSION: Transthoracic ASE is a good method to screen for PFO. Patients with suggestive of PFO had lower risk factors, less atherosclerosis, and better cardiac performance.

Features of Patients Receiving Extracorporeal Membrane Oxygenation Relative to Cardiogenic Shock Onset: A Single-Centre Experience.

Background and Objectives: Extracorporeal membrane oxygenation (ECMO) can be helpful in patients with cardiogenic shock associated with myocardial infarction, and its early use can improve the patient survival rate. In this study, we report a mortality rate-difference analysis that examined the time and location of shock occurrence. Materials and Methods: We enrolled patients who underwent ECMO due to cardiogenic shock related to myocardial infarction and assigned them to either a pre- or post-admission shock group. The primary outcome was the 1-month mortality rate; a subgroup analysis was conducted to assess the effect of bailout ECMO. Results: Of the 113 patients enrolled, 67 (38 with pre-admission shock, 29 with post-admission shock) were analysed. Asystole was more frequently detected in the pre-admission shock group than in the post-admission group. In both groups, the commonest culprit lesion location was in the left anterior descending artery. Cardiopulmonary resuscitation was performed significantly more frequently and earlier in the pre-admission group. The 1-month mortality rate was significantly lower in the pre-admission group than in the post-admission group. Male sex and ECMO duration (≥6 days) were factors significantly related to the reduced mortality rate in the pre-admission group. In the subgroup analysis, the mortality rate was lower in patients receiving bailout ECMO than in those not receiving it; the difference was not statistically significant. Conclusions: ECMO application resulted in lower short-term mortality rate among patients with out-of-hospital cardiogenic shock onset than with in-hospital shock onset; early cardiopulmonary resuscitation and ECMO might be helpful in select patients.

Capture of Single Silver Nanoparticles in Nanopore Arrays Detected by Simultaneous Amperometry and Surface-Enhanced Raman Scattering.

The attoliter volumes and confinement abilities of zero-dimensional nanopore-electrode arrays (NEAs) hold considerable promise for examining the behavior of single nanoparticles. In this work, we use surface-enhanced Raman scattering (SERS) in tandem with amperometry in order to monitor single Ag Raman-sentinel nanoparticles transported to and captured in single nanopores. To that end, highly ordered solid-state NEAs were fabricated to contain periodic arrays of nanopores, each housing a single recessed Au-ring electrode. These were used to electrostatically capture and trap single silver nanoparticles (AgNPs) functionalized with the electrochemically stable Raman reporter, 1,4-bis(2-methylstyryl)benzene (bis-MSB). Transport and capture of the bis-MSB-tagged AgNPs in the nanopores was followed by simultaneous amperometry and SERS signals characteristic of AgNP oxidation and enhanced Raman scattering by bis-MSB at silver-gold hot spots, respectively. The frequency and magnitude of oxidation-current spikes increased with stepwise increases in DC voltage, and characteristic bis-MSB SERS spectra were observed. Under AC excitation, on the other hand, two distinctly different types of SERS signals were observed, independent of frequency and amplitude: (1) strong, transient (<10 s) spectra and (2) slow (>100 s) monotonically diminishing spectra. We hypothesize that the former behavior results from AgNP aggregates, whereas the latter occurs as a result of multiple incomplete AgNP-oxidation events in succession. These results show that attoliter-volume NEAs are competent for acquiring concurrent SERS spectra and for amperometry of single nanoparticles and that together these measurements can illuminate the collision dynamics of nanoparticles in confined environments.

Voltage-Gated Nanoparticle Transport and Collisions in Attoliter-Volume Nanopore Electrode Arrays.

Single nanoparticle analysis can reveal how particle-to-particle heterogeneity affects ensemble properties derived from traditional bulk measurements. High-bandwidth, low noise electrochemical measurements are needed to examine the fast heterogeneous electron-transfer behavior of single nanoparticles with sufficient fidelity to resolve the behavior of individual nanoparticles. Herein, nanopore electrode arrays (NEAs) are fabricated in which each pore supports two vertically spaced, individually addressable electrodes. The top ring electrode serves as a particle gate to control the transport of silver nanoparticles (AgNPs) within individual attoliter volume NEAs nanopores, as shown by redox collisions of AgNPs collisions at the bottom disk electrode. The AgNP-nanoporeis system has wide-ranging technological applications as well as fundamental interest, since the transport of AgNPs within the NEA mimics the transport of ions through cell membranes via voltage-gated ion channels. A voltage threshold is observed above which AgNPs are able to access the bottom electrode of the NEAs, i.e., a minimum potential at the gate electrode is required to switch between few and many observed collision events on the collector electrode. It is further shown that this threshold voltage is strongly dependent on the applied voltage at both electrodes as well as the size of AgNPs, as shown both experimentally and through finite-element modeling. Overall, this study provides a precise method of monitoring nanoparticle transport and in situ redox reactions within nanoconfined spaces at the single particle level.

Direct-Write Formation and Dissolution of Silver Nanofilaments in Ionic Liquid-Polymer Electrolyte Composites.

Materials with reconfigurable optical properties are candidates for applications such as optical cloaking and wearable sensors. One approach to fabricate these materials is to use external fields to form and dissolve nanoscale conductive channels in well-defined locations within a polymer. In this study, conductive atomic force microscopy is used to electrochemically form and dissolve nanoscale conductive filaments at spatially distinct points in a polyethylene glycol diacrylate (PEGDA)-based electrolyte blended with varying amounts of ionic liquid (IL) and silver salt. The fastest filament formation and dissolution times are detected in a PEGDA/IL composite that has the largest modulus (several GPa) and the highest polymer crystal fraction. This is unexpected because filament formation and dissolution events are controlled by ion transport, which is typically faster within amorphous regions where polymer mobility is high. Filament kinetics in primarily amorphous and crystalline regions are measured, and two different mechanisms are observed. The formation time distributions show a power-law dependence in the crystalline regions, attributable to hopping-based ion transport, while amorphous regions show a normal distribution. The results indicate that the timescale of filament formation/dissolution is determined by local structure, and suggest that structure could be used to tune the optical properties of the film.

Zero-Mode Waveguide Nanophotonic Structures for Single Molecule Characterization.

Single-molecule characterization has become a crucial research tool in the chemical and life sciences, but limitations, such as limited concentration range, inability to control molecular distributions in space, and intrinsic phenomena, such as photobleaching, present significant challenges. Recent developments in non-classical optics and nanophotonics offer promising routes to mitigating these restrictions, such that even low affinity (K D ~ mM) biomolecular interactions can be studied. Here we introduce and review specific nanophotonic devices used to support single molecule studies. Optical nanostructures, such as zero-mode waveguides (ZMWs), are usually fabricated in thin gold or aluminum films and serve to confine the observation volume of optical microspectroscopy to attoliter to zeptoliter volumes. These simple nanostructures allow individual molecules to be isolated for optical and electrochemical analysis, even when the molecules of interest are present at high concentration (µM - mM) in bulk solution. Arrays of ZMWs may be combined with optical probes such as single molecule fluorescence, single molecule fluorescence resonance energy transfer (smFRET), and fluorescence correlation spectroscopy (FCS) for distributed analysis of large numbers of single-molecule reactions or binding events in parallel. Furthermore, ZMWs may be used as multifunctional devices, for example by combining optical and electrochemical functions in a single discrete architecture to achieve electrochemical ZMWs (E-ZMW). In this review, we will describe the optical properties, fabrication, and applications of ZMWs for single-molecule studies, as well as the integration of ZMWs into systems for chemical and biochemical analysis.

Electrochemistry at single molecule occupancy in nanopore-confined recessed ring-disk electrode arrays.

Electrochemical reactions at nanoscale structures possess unique characteristics, e.g. fast mass transport, high signal-to-noise ratio at low concentration, and insignificant ohmic losses even at low electrolyte concentrations. These properties motivate the fabrication of high density, laterally ordered arrays of nanopores, embedding vertically stacked metal-insulator-metal electrode structures and exhibiting precisely controlled pore size and interpore spacing for use in redox cycling. These nanoscale recessed ring-disk electrode (RRDE) arrays exhibit current amplification factors, AFRC, as large as 55-fold with Ru(NH3)62/3+, indicative of capture efficiencies at the top and bottom electrodes, Φt,b, exceeding 99%. Finite element simulations performed to investigate the concentration distribution of redox species and to assess operating characteristics are in excellent agreement with experiment. AFRC increases as the pore diameter, at constant pore spacing, increases in the range 200-500 nm and as the pore spacing, at constant pore diameter, decreases in the range 1000-460 nm. Optimized nanoscale RRDE arrays exhibit a linear current response with concentration ranging from 0.1 µM to 10 mM and a small capacitive current with scan rate up to 100 V s-1. At the lowest concentrations, the average pore occupancy is 〈n〉 ∼ 0.13 molecule establishing productive electrochemical signals at occupancies at and below the single molecule level in these nanoscale RRDE arrays.

Single occupancy spectroelectrochemistry of freely diffusing flavin mononucleotide in zero-dimensional nanophotonic structures.

Zero-mode waveguides (ZMW) have the potential to be powerful confinement tools for studying electron transfer dynamics at single molecule occupancy conditions. Flavin mononucleotide contains an isoalloxazine chromophore, which is fluorescent in the oxidized state (FMN) while the reduced state (FMNH2) exhibits dramatically lower light emission, i.e. a dark-state. This allows fluorescence emission to report the redox state of single FMN molecules, an observation that has been used previously to study single electron transfer events in surface-immobilized flavins and flavoenzymes, e.g. sarcosine oxidase, by direct wide-field imaging of ZMW arrays. Single molecule electron transfer dynamics have now been extended to the study of freely diffusing molecules using fluorescence measurements of Au ZMWs under single occupancy conditions. The Au in the ZMW serves both as an optical cladding layer and as the working electrode for potential control, thereby accessing single molecule electron transfer dynamics at µM concentrations. Consistent with expectations, the probability of observing single reduced molecules increases as the potential is scanned negative, E(appl) < E(eq), and the probability of observing emitting oxidized molecules increases at E(appl) > E(eq). Different single molecules exhibit different electron transfer properties as reflected in the position of E(eq) and the distribution of E(eq) among a population of FMN molecules. Two types of actively-controlled electroluminescence experiments were used: chronofluorometry experiments, in which the potential is alternately stepped between oxidizing and reducing potentials, and cyclic potential sweep fluorescence experiments, analogous to cyclic voltammetry, these latter experiments exhibiting a dramatic scan rate dependence with the slowest scan rates showing distinct intermediate states that are stable over a range of potentials. These states are assigned to flavosemiquinone species that are stabilized in the special environment of the ZMW nanopore.

Electrochemical signal amplification for immunosensor based on 3D interdigitated array electrodes.

We devised an electrochemical redox cycling based on three-dimensional interdigitated array (3D IDA) electrodes for signal amplification to enhance the sensitivity of chip-based immunosensors. The 3D IDA consists of two closely spaced parallel indium tin oxide (ITO) electrodes that are positioned not only on the bottom but also the ceiling, facing each other along a microfluidic channel. We investigated the signal intensities from various geometric configurations: Open-2D IDA, Closed-2D IDA, and 3D IDA through electrochemical experiments and finite-element simulations. The 3D IDA among the four different systems exhibited the greatest signal amplification resulting from efficient redox cycling of electroactive species confined in the microchannel so that the faradaic current was augmented by a factor of ∼100. We exploited the enhanced sensitivity of the 3D IDA to build up a chronocoulometric immunosensing platform based on the sandwich enzyme-linked immunosorbent assay (ELISA) protocol. The mouse IgGs on the 3D IDA showed much lower detection limits than on the Closed-2D IDA. The detection limit for mouse IgG measured using the 3D IDA was ∼10 fg/mL, while it was ∼100 fg/mL for the Closed-2D IDA. Moreover, the proposed immunosensor system with the 3D IDA successfully worked for clinical analysis as shown by the sensitive detection of cardiac troponin I in human serum down to 100 fg/mL.

Operando spectroscopic characterization of formamidinium lead iodide perovskite quantum dots for tracking electrochemical reactions.

Multidimensional ABX3 hybrid perovskites three-dimensionally confined dot-shaped structure demonstrate versatile potential to photoelectrochemical cells for water splitting, hydrogen generation, solar cells, and light-emitting diodes. To apply perovskite quantum dots (PQDs) to solar-driven chemistry and optoelectronic devices, understanding the photoinduced charge carrier dynamics of PQDs under electrochemical conditions or applied bias are important. In this study, the detailed transformation mechanism of formamidinium lead iodide perovskite quantum dots under electrochemical conditions was studied by tracking the products of the reaction through cyclic voltammetry, X-ray photoemission spectroscopy, in-situ UV-visible spectroelectrochemistry, etc. Through comprehensive characterizations, the mechanism of irreversible oxidative transformation of perovskite quantum dots was presented. This study provides deeper insight into the electrochemical behavior of PQDs for successful solar-driven chemistry and optoelectronic device applications.

Fourth dose of microneedle array patch of SARS-CoV-2 S1 protein subunit vaccine elicits robust long-lasting humoral responses in mice.

The COVID-19 pandemic has underscored the pressing need for safe and effective booster vaccines, particularly in considering the emergence of new SARS-CoV-2 variants and addressing vaccine distribution inequalities. Dissolving microneedle array patches (MAP) offer a promising delivery method, enhancing immunogenicity and improving accessibility through the skin's immune potential. In this study, we evaluated a microneedle array patch-based S1 subunit protein COVID-19 vaccine candidate, which comprised a bivalent formulation targeting the Wuhan and Beta variant alongside a monovalent Delta variant spike proteins in a murine model. Notably, the second boost of homologous bivalent MAP-S1(WU + Beta) induced a 15.7-fold increase in IgG endpoint titer, while the third boost of heterologous MAP-S1RS09Delta yielded a more modest 1.6-fold increase. Importantly, this study demonstrated that the administration of four doses of the MAP vaccine induced robust and long-lasting immune responses, persisting for at least 80 weeks. These immune responses encompassed various IgG isotypes and remained statistically significant for one year. Furthermore, neutralizing antibodies against multiple SARS-CoV-2 variants were generated, with comparable responses observed against the Omicron variant. Overall, these findings emphasize the potential of MAP-based vaccines as a promising strategy to combat the evolving landscape of COVID-19 and to deliver a safe and effective booster vaccine worldwide.

Upregulation of TrkB by forskolin facilitated survival of MSC and functional recovery of memory deficient model rats.

Mesenchymal stem cells (MSCs) are effective vectors in delivering a gene of interest into degenerating brain. In ex vivo gene therapy, viability of transplanted MSCs is correlated with the extent of functional recovery. It has been reported that BDNF facilitates survival of MSCs but dividing MSCs do not express the BDNF receptor, TrkB. In this study, we found that the expression of TrkB is upregulated in human MSCs by the addition of forskolin (Fsk), an activator of adenylyl cyclase. To increase survival rate of MSCs and their secretion of tropic factors that enhance regeneration of endogenous cells, we pre-exposed hMSCs with Fsk and transduced with BDNF-adenovirus before transplantation into the brain of memory deficient rats, a degenerating brain disease model induced by ibotenic acid injection. Viability of MSCs and expression of a GABA synthesizing enzyme were increased. The pre-treatment improved learning and memory, as detected by the behavioral tests including Y-maze task and passive avoidance test. These results suggest that TrkB expression of hMSCs elevates the neuronal regeneration and efficiency of BDNF delivery for treating degenerative neurological diseases accompanying memory loss.

Prevalence of stable coronary artery disease and its associated clinical factors among patients with chest pain and elevated cardiac troponin alone.

Cardiac troponin is a useful test for diagnosing cardiogenic causes in patients with chest pain. However, cardiac troponin levels are often elevated in patients with chest pain due to non-cardiac causes other than coronary artery disease. The purpose of this study was to investigate the prevalence of coronary artery disease (CAD) and its associated factors in patients with chest pain and elevated cardiac troponin I (cTnI). 104 patients (mean age, 65 ± 11 years; 60 [58%] men) who underwent coronary angiography (CAG) for chest pain and elevated cTnI levels were enrolled in this study. All patients had a normal CK-MB range and did not show any ischemic changes on electrocardiography or echocardiography. Patients were classified into two groups according to the presence of CAD (Group 1, n = 62) and the absence of CAD (Group 2, n = 42). Patients were classified into subgroups according to the presence (Group 2a, microvascular angina [MVA], n = 18) and absence (Group 2b, non-angina [NA], n = 25) of angina. CAD was diagnosed in 62 (60%) patients and MVA was suspected in 18 (17%) patients without CAD. Patients with CAD showed elevated blood pressure and slightly decreased heart rate. Diabetes mellitus was more prevalent in patients with CAD and patients without CAD (esp. with MVA) were more likely to be common drinkers. Increased relative wall thickness (RWT) and reduced E' velocity were associated with CAD. High-density lipoprotein (HDL) levels were reduced in patients with CAD and MVA but were higher in patients with NA. Lower HDL level was found to be independently associated with the presence of CAD. Elevated cTn1 levels without other evidence of myocardial ischemia are sufficient for performing CAG in patients with stable chest pain.

Attenuation of ischemia-reperfusion injury by intracoronary chelating agent administration.

Ischemia-reperfusion (IR) injury accelerates myocardial injury sustained during the myocardial ischemic period and thus abrogates the benefit of reperfusion therapy in patients with acute myocardial infarction. We investigated the efficacy of intracoronary ethylenediaminetetraacetic acid (EDTA) administration as an adjunctive treatment to coronary intervention to reduce IR injury in a swine model. We occluded the left anterior descending artery for 1 h. From the time of reperfusion, we infused 50 mL of EDTA-based chelating agent via the coronary artery in the EDTA group and normal saline in the control group. IR injury was identified by myocardial edema on echocardiography. Tetrazolium chloride assay revealed that the infarct size was significantly lower in the EDTA group than in the control group, and the salvage percentage was higher. Electron microscopy demonstrated that the mitochondrial loss in the cardiomyocytes of the infarcted area was significantly lower in the EDTA group than in the control group. Echocardiography after 4 weeks showed that the remodeling of the left ventricle was significantly less in the EDTA group than in the control group: end-diastolic dimension 38.8 ± 3.3 mm vs. 43.9 ± 3.7 mm (n = 10, p = 0.0089). Left ventricular ejection fraction was higher in the EDTA group (45.3 ± 10.3 vs. 34.4 ± 11.8, n = 10, respectively, p = 0.031). In a swine model, intracoronary administration of an EDTA chelating agent reduced infarct size, mitochondrial damage, and post-infarct remodeling. This result warrants further clinical study evaluating the efficacy of the EDTA chelating agent in patients with ST-segment elevation myocardial infarction.