ABSTRACT
The toxicity of methylmercury (MeHg) during embryonic development is a relevant issue that remains unclear and deserves investigation. In this sense, there is evidence that links the intake of contaminated food with cardiovascular pathologies in human adults and children. Thus, this study aimed to verify the impact of MeHg on the structure and integrity of extraembryonic and cardiac blood vessels and the contractile function of cardiomyocytes, also evaluating embryonic weight and the cardiosomatic index (CSI). Thus, chicken embryos, used as an experimental model, were exposed to a single dose of 0.1 µg MeHg/50 µl saline at E1.5 and analyzed at E10. After exposure, an increase in the number of extraembryonic blood vessels and the veins of the cardiac tissue was observed. These increases were accompanied by a reduction in the content of VEGF and VCAM proteins related to vessel growth and adhesiveness. Together, these results were related to reduced nitrite (NOx) levels. Furthermore, MeHg reduces the number of sarcomeres and increases the content of cardiac troponin I (cTnI), a protein that regulates contraction. In general, exposure to MeHg affected the integrity of extraembryonic and cardiac vessels and the contractile function of cardiomyocytes, which had a systemic impact evidenced by the reduction in embryonic weight gain and CSI.
Subject(s)
Methylmercury Compounds , Myocardial Contraction , Myocytes, Cardiac , Myocytes, Cardiac/drug effects , Animals , Chick Embryo , Methylmercury Compounds/toxicity , Myocardial Contraction/drug effects , Embryonic Development/drug effects , Coronary Vessels/drug effects , Troponin I/metabolismABSTRACT
BACKGROUND: Chemotherapy with doxorubicin may lead to left ventricular dysfunction. There is a controversial recommendation that biomarkers can predict ventricular dysfunction, which is one of the most feared manifestations of anthracycline cardiotoxicity. OBJECTIVE: The aim of this study was to evaluate the behavior of biomarkers such as Troponin I, type B natriuretic peptide, creatine phosphokinase fraction MB, and myoglobin in predicting cardiotoxicity in a cohort of women with breast cancer undergoing chemotherapy with anthracycline. METHODS: This is an observational, prospective, longitudinal, unicentric study, which included 40 women with breast cancer, whose therapeutic proposal included treatment with doxorubicin. The protocol had a clinical follow-up of 12 months. Biomarkers such as Troponin I, type B natriuretic peptide, creatine phosphokinase fraction MB, and myoglobin were measured pre-chemotherapy and after the first, third, fourth, and sixth cycles of chemotherapy. RESULTS: There was a progressive increase in type B natriuretic peptide and myoglobin values in all chemotherapy cycles. Although creatine phosphokinase fraction MB showed a sustained increase, this increase was not statistically significant. Troponin, type B natriuretic peptide, myoglobin, and creatine phosphokinase fraction MB were the cardiotoxicity markers with the earliest changes, with a significant increase after the first chemotherapy session. However, they were not able to predict cardiotoxicity. CONCLUSION: Troponin I, type B natriuretic peptide, myoglobin, and creatine phosphokinase fraction MB are elevated during chemotherapy with doxorubicin, but they were not able to predict cardiotoxicity according to established clinical and echocardiographic criteria. The incidence of subclinical cardiotoxicity resulting from the administration of doxorubicin was 12.5%.
Subject(s)
Biomarkers , Breast Neoplasms , Cardiotoxicity , Doxorubicin , Myoglobin , Troponin I , Humans , Female , Breast Neoplasms/drug therapy , Prospective Studies , Troponin I/blood , Doxorubicin/adverse effects , Cardiotoxicity/etiology , Middle Aged , Biomarkers/blood , Myoglobin/blood , Adult , Antibiotics, Antineoplastic/adverse effects , Natriuretic Peptide, Brain/blood , Aged , Creatine Kinase, MB Form/blood , Longitudinal Studies , Anthracyclines/adverse effects , Ventricular Dysfunction, Left/chemically induced , Predictive Value of TestsABSTRACT
BACKGROUND: Ablation Index (AI) software has allowed better atrial fibrillation (AF) ablation results, but recurrence rates remain significant. Specific serum biomarkers have been associated with this recurrence. OBJECTIVES: To evaluate whether certain biomarkers could be used (either individually or combined) to predict arrhythmia recurrence after AI-guided AF ablation. METHODS: Prospective multicenter observational study of consecutive patients referred for AF ablation from January 2018 to March 2021. Hemoglobin, brain natriuretic peptide (BNP), C-reactive protein, high sensitivity cardiac troponin I, creatinine clearance, thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were assessed for their ability to predict arrhythmia recurrence during follow-up. Statistical significance was accepted for p values of<0.05. RESULTS: A total of 593 patients were included - 412 patients with paroxysmal AF and 181 with persistent AF. After a mean follow-up of 24±6 months, overall single-procedure freedom from atrial arrhythmia was 76.4%. Individually, all biomarkers had no or only modest predictive power for recurrence. However, a TSH value >1.8 µUI/mL (HR=1.82 [95% CI, 1.89-2.80], p=0.006) was an independent predictor of arrhythmia recurrence. When assessing TSH, FT4 and BNP values in combination, each additional "abnormal" biomarker value was associated with a lower freedom from arrhythmia recurrence (87.1 % for no biomarker vs. 83.5% for one vs. 75.1% for two vs. 43.3% for three biomarkers, p<0.001). Patients with three "abnormal" biomarkers had a threefold higher risk of AF recurrence compared with no "abnormal" biomarker (HR=2.88 [95% CI, 1.39-5.17], p=0.003). CONCLUSIONS: When used in combination, abnormal TSH, FT4 and BNP values can be a useful tool for predicting arrhythmia recurrence after AI-guided AF ablation.
FUNDAMENTO: O software ablation index (AI) permitiu melhorar os resultados da ablação de fibrilação atrial (FA), mas as taxas de recorrência permanecem significativas. Biomarcadores séricos específicos têm sido associados a essa recorrência. OBJETIVOS: Avaliar se certos biomarcadores podem ser utilizados (individualmente ou combinados) para predizer a recorrência de FA pós ablação guiada pelo AI. MÉTODOS: Estudo multicêntrico, observacional, prospectivo de pacientes consecutivos, encaminhados para ablação de FA de janeiro de 2018 a março de 2021. Hemoglobina, peptídeo natriurético cerebral (BNP), proteína C reativa, troponina I ultrassensível, clearance de creatinina, Hormônio Tireoestimulante (TSH), e Tiroxina livre (T4) foram avaliados quanto à capacidade de prever a recorrência de arritmias durante o acompanhamento. Valores de p <0,05 foram aceitos como estatisticamente significativos. RESULTADOS: Um total de 593 pacientes foram incluídos 412 com FA paroxística e 181 com FA persistente. Durante o seguimento médio de 24±6 meses, 76,4% não apresentaram recidiva após ablação. Individualmente, os biomarcadores demonstraram um valor preditivo baixo ou nulo para recorrência. No entanto, TSH >1,8 µUI/mL [HR=1,82 (IC95%, 1,89-2,80), p=0,006] foi um preditor independente de recorrência. Avaliando-se a combinação de TSH, FT4 e BNP, a adição de cada valor "anormal" foi associada a uma menor sobrevida livre de recorrência (87,1% se nenhum vs. 83,5% se um vs. 75,1% se dois vs. 43,3% se três biomarcadores, p<0,001). Doentes com três biomarcadores "anormais" apresentaram três vezes maior probabilidade de recorrência de FA, comparativamente aos que não apresentaram nenhum biomarcador "anormal" (HR=2,88 [IC95%, 1,39-5,17], p=0,003). CONCLUSÕES: Quando combinados, valores anormais de TSH, FT4 e BNP podem ser uma ferramenta útil para prever a recorrência de FA pós ablação guiada pelo AI.
Subject(s)
Atrial Fibrillation , Biomarkers , Catheter Ablation , Recurrence , Thyrotropin , Humans , Atrial Fibrillation/surgery , Atrial Fibrillation/blood , Biomarkers/blood , Male , Female , Prospective Studies , Middle Aged , Catheter Ablation/methods , Aged , Thyrotropin/blood , Natriuretic Peptide, Brain/blood , Predictive Value of Tests , C-Reactive Protein/analysis , Treatment Outcome , Thyroxine/blood , Risk Factors , Troponin I/bloodSubject(s)
Acute Coronary Syndrome , Myocardial Infarction , Humans , Acute Coronary Syndrome/diagnosis , Troponin I , BiomarkersABSTRACT
Numerous studies have been published suggesting that troponin levels are related to adverse outcomes in chronic cardiac and non-cardiac conditions. Our study investigated whether troponin levels gathered from unselected blood samples taken during outpatient care are associated with adverse outcomes in a population with stable coronary artery disease. In a cohort of 949 patients with stable coronary artery disease, an average age of 67.5 ± 9.5 years, 69.5% male, 52.1% diabetics, 51.6% with previous myocardial infarction, and 57.9% with triple-vessel disease, 21.7% of patients encountered new events during an average period of monitoring of 2.07 ± 0.81 years. Troponin I/99th percentile categorized into tertiles emerged as an independent predictor of death and combined events risk (hazard ratio: 2.02 (1.13-3.60), p = 0.017; 2.30 (1.37-3.88, p = 0.002, respectively). A troponin ratio > 0.24 was able to identify 53.3% of patients at risk of death and heart failure hospitalization. In patients with stable coronary artery disease who are adherent to treatment, troponin levels are independently associated with death and heart failure hospitalization in a medium-term follow-up.
Subject(s)
Coronary Artery Disease , Heart Failure , Humans , Male , Middle Aged , Aged , Female , Troponin I , Outpatients , BiomarkersABSTRACT
Background: Coronavirus disease 2019 (COVID-19) can cause cardiac injury, probably associated with myocarditis and ischemia induced by the infection. Myocardial damage leads to the liberation of proinflammatory cytokines and to the activation of autoimmune adaptive mechanisms through molecular limitation. Objective: To assess mortality associated with myocardial damage in hospitalized patients with COVID-19 confirmed by troponin I measurement. Material and methods: Case-control study nested in a cohort of patients of a third-level hospital. Descriptive statistics were used to characterize the population. Qualitative variables were expressed as proportions and ranges, quantitative variables as means and standard deviation. Fisher's exact test was used to compare mortality between patients with and without myocardial damage. A p value < 0.05 was considered significant. Results: From June 2020 to August 2020, 28 patients who met the selection criteria were enrolled, out of which 15 had no myocardial damage and 13 had myocardial damage assessed by serum troponin measurement. A strong association was found between mortality and the presence of myocardial damage, since mortality was 20% (3/15) among patients without myocardial damage and 92.3% (12/13) among those with myocardial damage (Fisher's exact test, p < 0.005). Conclusion: Mortality in patients with COVID-19 is associated with myocardial damage assessed by troponin I measurement.
Introducción: la enfermedad por coronavirus del 2019 (COVID-19) puede causar lesión cardiaca, probablemente asociada con miocarditis e isquemias inducidas por la infección. El daño miocárdico conduce a la liberación de citocinas proinflamatorias y a la activación de mecanismos adaptativos de tipo autoinmune por medio de la limitación molecular. Objetivo: evaluar la mortalidad asociada a daño miocárdico en pacientes hospitalizados con COVID-19 confirmado mediante la medición de troponina I. Material y métodos: estudio de casos y controles anidado en una cohorte de los pacientes de un hospital de tercer nivel. Se utilizó estadística descriptiva para caracterizar a la población. Las variables cualitativas se expresaron como proporciones y rangos, las cuantitativas como medias y desviación estándar. Para comparar la mortalidad entre pacientes con y sin daño miocárdico se utilizó la prueba exacta de Fisher. Valores de p < 0.05 fueron significativos. Resultados: de junio del 2020 a agosto del 2020 se enrolaron 28 pacientes que cumplieron los criterios de selección, de los cuales 15 no tuvieron daño miocárdico y 13 tuvieron daño miocárdico evaluado con la medición de troponina sérica. Se encontró fuerte asociación entre la mortalidad y la presencia de daño miocárdico, ya que se registró mortalidad del 20% (3/15) entre los pacientes sin daño miocárdico y de 92.3% (12/13) entre los que tuvieron daño miocárdico (prueba exacta de Fisher: p < 0.005). Conclusiones: la mortalidad en pacientes con COVID-19 se asocia a daño miocárdico evaluado a través de la medición de troponina I.
Subject(s)
COVID-19 , Humans , COVID-19/complications , COVID-19/epidemiology , Troponin I , Case-Control Studies , SARS-CoV-2ABSTRACT
INTRODUCTION: Zika virus infection during pregnancy causes fetal microcephaly and brain damage. Congenital Zika syndrome (CZS) is characterized by systemic involvement with diffuse muscle impairment, a high frequency of arthrogryposis, and microphthalmia. Cardiac impairment in CZS has rarely been evaluated. Our study assessed morphology and biventricular cardiac function in children with CZS and advanced neurological dysfunction. METHODS: This cross-sectional study was conducted on 52 children with CZS (Zika group; ZG) and 25 healthy children (control group; CG) in Paraiba, Brazil. Clinical evaluation, electrocardiogram (EKG), and transthoracic echocardiogram (TTE) were performed on all children. Additionally, troponin I and natriuretic peptide type B (BNP) levels, the degree of cerebral palsy, and neuroimaging findings were assessed in the ZG group. RESULTS: The median age of the study population was 5 years in both groups, and 40.4% (ZG) and 60% (CG) were female. The most prevalent electrocardiographic alteration was sinus arrhythmia in both the ZG (n = 9, 17.3%) and CG (n = 4, 16%). The morphological parameters adjusted for Z score were as follows: left ventricular (LV) end-diastolic diameter in ZG: -2.36 [-5.10, 2.63] vs. CG: -1.07 [-3.43, 0.61], p<0.001); ascending aorta (ZG: -0.09 [-2.08, 1.60] vs. CG: 0.43 [-1.47, 2.2], p = 0.021); basal diameter of the right ventricle (RV) (ZG: -2.34 [-4.90, 0.97] vs. CG: -0.96 [-2.21, 0.40], p<0.01); and pulmonary artery dimension (ZG: -2.13 [-5.99, 0.98] vs. CG: -0.24 [-2.53, 0.59], p<0.01). The ejection fractions (%) were 65.7 and 65.6 in the ZG and CG, respectively (p = 0.968). The left atrium volume indices (mL/m2) in the ZG and CG were 13.15 [6.80, 18.00] and 18.80 [5.90, 25.30] (p<0.01), respectively, and the right atrium volume indices (mL/m2) were 10.10 [4.90, 15.30] and 15.80 [4.10, 24.80] (p<0.01). The functional findings adjusted for Z score were as follows: lateral systolic excursion of the mitral annular plane (MAPSE) (ZG: 0.36 [-2.79, 4.71] vs. CG: 1.79 [-0.93, 4.5], p = 0.001); tricuspid annular plane systolic excursion (TAPSE) (ZG: -2.43 [-5.47, 5.09] vs. CG: 0.07 [-1.98, 3.64], p<0.001); and the S' of the RV (ZG: 1.20 [3.35, 2.90] vs. CG: -0.20 [-2.15, 1.50], p = 0.0121). No differences in biventricular strain measurements were observed between the groups. Troponin I and BNP levels were normal in in the ZG. Grade V cerebral palsy and subcortical calcification were found in 88.6% and 97.22% of children in the ZG group, respectively. CONCLUSION: A reduction in cardiac dimensions and functional changes were found in CZS patients, based on the TAPSE, S' of the RV, and MAPSE, suggesting the importance of cardiac evaluation and follow-up in this group of patients.
Subject(s)
Cerebral Palsy , Zika Virus Infection , Zika Virus , Child , Humans , Female , Child, Preschool , Male , Zika Virus Infection/complications , Cross-Sectional Studies , Troponin I , EchocardiographyABSTRACT
This work describes the development of a membraneless, self-powered immunosensor exploiting a photoelectrochemical system based on two photoelectrodes for cardiac troponin I (cTn). An electrode based on CaBi2Ta2O9 combined with bismuth oxyiodides (BiOI/Bi4O5I2/Bi5O7I) was modified with the cTnI antibody (anti-cTnI) and applied in a photoelectrochemical cell as a photoanode. To perform the cTnI detection exploiting a self-powered photoelectrochemical setup, the immunosensor (anti-cTnI/BiOI/Bi4O5I2/Bi5O7I/CaBi2Ta2O9/FTO) was coupled to a photoelectrochemical cell containing a photocathode based on CuBi2O4 (CBO/FTO) for zero-biased photoelectrochemical immunosensing of cardiac troponin I (cTnI) biomarker. For comparison purposes, the photoanode was applied for cTnI detection in a three-electrode electrochemical cell. The spectroscopic, structural, and morphological characteristics of the photoelectrochemical (PEC) materials were evaluated using scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and X-ray diffraction (XRD). Electrochemical impedance spectroscopy (EIS) measurements were performed in the presence and absence of light to investigate the effects of photons on the charge transfer resistance of the photoanode. The influence of the cTnI biomarker on the photoelectrochemical response of the anti-cTnI antibody-modified photoelectrochemical platform (anti-cTnI/BiOI/Bi4O5I2/Bi5O7I/CaBi2Ta2O9/FTO) was evaluated by measuring the photocurrent of the system. The immunosensor presented a linear response ranging from 1 pg mL-1 to 200 ng mL-1 as well as a mean recovery percentage between 95.7% and 108.0% in real human serum samples for the cTnI biomarker.
Subject(s)
Biosensing Techniques , Electrochemical Techniques , Humans , Electrochemical Techniques/methods , Immunoassay/methods , Bismuth/chemistry , Biosensing Techniques/methods , Troponin I , Biomarkers , Alpha-Ketoglutarate-Dependent Dioxygenase FTOABSTRACT
INTRODUCTION: Stable angina develops during physical activity or stress, and it is typically an aspect of Coronary Heart Disease (CHD) that can lead to arrhythmia, heart failure and even sudden death. ANRIL, an Antisense Noncoding RNA gene in the INK4 Locus, is associated with multiple disorders including CHD; however, expressional levels of ANRIL in between patients with stable angina and myocardial infarction, one of the acute coronary syndrome, have not been clarified yet. METHODS: The authors enrolled 62 patients with myocardial infarction and 59 with stable angina before primary percutaneous coronary intervention, as well as 48 healthy volunteers. Their peripheral blood was collected for analysis of ANRIL and cardiac troponin I, a traditional diagnostic index of CHD by real-time PCR. RESULTS: The data showed that ANRIL is a better diagnostic indicator than cardiac troponin I in patients with stable angina and that the levels of ANRIL are higher in patients with stable angina than those with the myocardial infarction. DISCUSSION: The levels of ANRIL in peripheral plasma could be used as a good biomarker for stable angina.
Subject(s)
Angina, Stable , Myocardial Infarction , RNA, Long Noncoding , Humans , RNA, Long Noncoding/genetics , Angina, Stable/genetics , Troponin I , RNA, AntisenseABSTRACT
Troponin is the American College of Cardiology and American Heart Association preferred biomarker for diagnosing acute myocardial infarction (MI). We provide a modeling framework for high sensitivity cardiac Troponin I (hs-cTnI) detection in chromatographic immunoassays (flow displacement mode) with an analytical limit of detection, i.e., LOD < 10 ng/L. We show that each of the various control parameters exert a significant influence over the design requirements to reach the desired LOD. Additionally, the design implications in a multiplexed fluidic network, as in the case of Simple Plex™ Ella instrument, are significantly affected by the choice of the number of channels or partitions in the network. We also provide an upgrade on the existing LOD equation to evaluate the necessary minimum volume to detect a particular concentration by considering the effects of stochastics and directly incorporating the target number of copies in each of the partitions in case of multiplexed networks. Even though a special case of cTnI has been considered in this study, the model and analysis are analyte agnostic and may be applied to a wide class of chromatographic immunoassays. We believe that this contribution will lead to more efficient designing of the immunochromatographic assays.
Subject(s)
Myocardial Infarction , Troponin I , Humans , Myocardial Infarction/diagnosis , Biomarkers , Immunoassay , Troponin TABSTRACT
AIMS: Chest pain is a major cause of medical evaluation at emergency department (ED) and demands observation to exclude the diagnosis of acute myocardial infarction (AMI). High-sensitivity cardiac troponin assays used as isolated measure and by 0- and 1-h algorithms are accepted as a rule-in/rule-out strategy, but there is a lack of validation in specific populations. METHODS AND RESULTS: The IN-HOspital Program to systematizE Chest Pain Protocol (IN-HOPE study) is a multicentre study that prospectively included patients admitted to the ED due to suspected symptoms of AMI at 16 sites in Brazil. Medical decisions of all patients followed the standard approach of 0 h/3 h protocol, but, in addition, blood samples were also collected at 0 and 1 h and sent to a central laboratory (core lab) to measure high-sensitivity cardiac troponin T (hs-cTnT). To assess the theoretical performance of 0 h/1 h algorithm, troponin < 12 ng/L with a delta < 3 was considered rule-out while a value ≥ 52 or a delta ≥ 5 was considered a rule-in criterion (the remaining were considered as observation group). The main objective of the study was to assess, in a population managed by the 0 h/3 h protocol, the accuracy of 0 h/1 h algorithm overall and in groups with a higher probability of AMI. All patients were followed up for 30 days, and potential events were adjudicated. In addition to the prospective cohort, a retrospective analysis was performed assessing all patients with hs-cTnT measured during the year of 2021 but not included in the prospective cohort, regardless of the indication of the test. A total of 5.497 patients were included (583 in the prospective and 4.914 in the retrospective analysis). The prospective cohort had a mean age of 57.3 (± 14.8) and 45.6% of females with a mean HEART score of 4.0 ± 2.2. By the core lab analysis, 74.4% would be eligible for a rule-out approach (45.3% of them with a HEART score > 3) while 7.3% would fit the rule-in criteria. In this rule-out group, the negative predictive value for index AMI was 100% (99.1-100) overall and regardless of clinical scores. At 30 days, no death or AMI occurred in the rule-out group of both 0/1 and 0/3 h algorithms while 52.4% of the patients in the rule-in group (0 h/1 h) were considered as AMI by adjudication. In the observation group (grey zone) of 0 h/1 h algorithm, GRACE discriminated the risk of these patients better than HEART score. In the retrospective analysis, 1.091 patients had a troponin value of <5 ng/L and there were no cardiovascular deaths at 30 days in this group. Among all 4.914 patients, the 30-day risk of AMI or cardiovascular death increased according to the level of troponin: 0% in the group < 5 ng/L, 0.6% between 5 and 14 ng/L, 2.2% between 14 and 42 ng/L, 6.3% between 42 and 90 ng/L, and 7.7% in the level ≥ 90 ng/L. CONCLUSION: In this large multicentre study, a 0 h/1 h algorithm had the potential to classify as rule-in or rule-out in almost 80% of the patients. The rule-out protocol had high negative predictive value regardless of clinical risk scores. Categories of levels of hs-cTn T also showed good accuracy in discriminating risk of the patients with a very favourable prognosis for cardiovascular death in the group with value < 5 ng/L. CLINICALTRIALS.GOV: NCT04756362.
Subject(s)
Myocardial Infarction , Troponin T , Female , Humans , Middle Aged , Algorithms , Biomarkers , Chest Pain/diagnosis , Chest Pain/etiology , Emergency Service, Hospital , Myocardial Infarction/diagnosis , Myocardial Infarction/epidemiology , Prospective Studies , Retrospective Studies , Troponin I , Male , Adult , AgedABSTRACT
Lateral flow assays (LFAs) have emerged as one of the most prominent paper-based biosensor platforms for rapidly detecting and quantifying analytes. Their selectivity, cost-effectiveness, efficiency, and simplicity make them ideal candidates for point-of-care (POC) applications, particularly when time-sensitive decisions are needed, such as cardiovascular events. The profound impact of cardiovascular diseases (CVDs), characterized by their high morbidity, mortality, and rehospitalization rates, necessitates an optimized approach for the early detection of cardiac muscle damage. This comprehensive review aims to consolidate the existing scientific literature on LFAs that specifically target cardiovascular biomarkers, including myoglobin and cardiac troponin I, over the past decade. By examining the advancements and findings in this field, valuable insights can be gained regarding the potential and future directions of LFAs in cardiovascular diagnostics.
Subject(s)
Cardiovascular Diseases , Point-of-Care Systems , Humans , Biomarkers , Troponin I , Cardiovascular Diseases/diagnosisABSTRACT
BACKGROUND: Skeletal muscle generates force and movements and maintains posture. Under pathological conditions, muscle fibers suffer an imbalance in protein synthesis/degradation. This event causes muscle mass loss and decreased strength and muscle function, a syndrome known as sarcopenia. Recently, our laboratory described secondary sarcopenia in a chronic cholestatic liver disease (CCLD) mouse model. Interestingly, the administration of ursodeoxycholic acid (UDCA), a hydrophilic bile acid, is an effective therapy for cholestatic hepatic alterations. However, the effect of UDCA on skeletal muscle mass and functionality has never been evaluated, nor the possible involved mechanisms. METHODS: We assessed the ability of UDCA to generate sarcopenia in C57BL6 mice and develop a sarcopenic-like phenotype in C2C12 myotubes and isolated muscle fibers. In mice, we measured muscle strength by a grip strength test, muscle mass by bioimpedance and mass for specific muscles, and physical function by a treadmill test. We also detected the fiber's diameter and content of sarcomeric proteins. In C2C12 myotubes and/or isolated muscle fibers, we determined the diameter and troponin I level to validate the cellular effect. Moreover, to evaluate possible mechanisms, we detected puromycin incorporation, p70S6K, and 4EBP1 to evaluate protein synthesis and ULK1, LC3 I, and II protein levels to determine autophagic flux. The mitophagosome-like structures were detected by transmission electron microscopy. RESULTS: UDCA induced sarcopenia in healthy mice, evidenced by decreased strength, muscle mass, and physical function, with a decline in the fiber's diameter and the troponin I protein levels. In the C2C12 myotubes, we observed that UDCA caused a reduction in the diameter and content of MHC, troponin I, puromycin incorporation, and phosphorylated forms of p70S6K and 4EBP1. Further, we detected increased levels of phosphorylated ULK1, the LC3II/LC3I ratio, and the number of mitophagosome-like structures. These data suggest that UDCA induces a sarcopenic-like phenotype with decreased protein synthesis and autophagic flux. CONCLUSIONS: Our results indicate that UDCA induces sarcopenia in mice and sarcopenic-like features in C2C12 myotubes and/or isolated muscle fibers concomitantly with decreased protein synthesis and alterations in autophagic flux.
Subject(s)
Sarcopenia , Mice , Animals , Sarcopenia/chemically induced , Sarcopenia/pathology , Ursodeoxycholic Acid/pharmacology , Ursodeoxycholic Acid/metabolism , Ribosomal Protein S6 Kinases, 70-kDa/metabolism , Troponin I/metabolism , Mice, Inbred C57BL , Muscle, Skeletal/metabolismABSTRACT
BACKGROUND: Cardiac troponin detected with sensitive assays can be chronically elevated, in the absence of unstable coronary syndromes. In patients with chronic coronary artery disease, clinically silent ischemic episodes may cause chronic troponin release. T1 mapping is a cardiovascular magnetic resonance technique useful in quantitative cardiac tissue characterization. We selected patients with anatomically and functionally normal hearts to investigate associations between chronic troponin release and myocardial tissue characteristics assessed by T1 mapping. METHODS: We investigated the relationship between cardiac troponin I concentrations and cardiovascular magnetic resonance T1 mapping parameters in patients with stable coronary artery disease enrolled in MASS V study before elective revascularization. Participants had no previous myocardial infarction, negative late gadolinium enhancement, normal left ventricular function, chamber dimensions and wall thickness. RESULTS: A total of 56 patients were analyzed in troponin tertiles: nativeT1 and extracellular volume (ECV) values (expressed as meansâ ±â standard deviations) increased across tertiles: nativeT1 (1006â ±â 27 ms vs 1016â ±â 27 ms vs 1034â ±â 37 ms, ptrendâ =â 0.006) and ECV (22â ±â 3% vs 23â ±â 1.9% vs 25â ±â 3%, ptrendâ =â 0.007). Cardiac troponin I concentrations correlated with native T1(Râ =â 0.33, Pâ =â .012) and ECV (Râ =â 0.3, Pâ =â .025), and were independently associated with nativeT1 (Pâ =â .049) and ventricular mass index (Pâ =â .041) in multivariable analysis. CONCLUSION: In patients with chronic coronary artery disease and structurally normal hearts, troponin I concentrations correlated with T1 mapping parameters, suggesting that diffuse edema or fibrosis scattered in normal myocardium might be associated with chronic troponin release.
Subject(s)
Coronary Artery Disease , Humans , Coronary Artery Disease/diagnosis , Coronary Artery Disease/pathology , Contrast Media , Troponin I , Magnetic Resonance Imaging, Cine , Gadolinium , Myocardium/pathology , Fibrosis , Ventricular Function, Left , Predictive Value of TestsABSTRACT
OBJECTIVE: A reliable predictor is needed for non-ST-elevation myocardial infarction patients with high mortality risk. The aim of this study was to assess the effectiveness of the Global Registry of Acute Coronary Events and Quick Sequential Organ Failure Assessment-Troponin (qSOFA-T) scores on in-hospital mortality rate in non-ST-elevation myocardial infarction patients. METHODS: This is an observational and retrospective study. Patients admitted to the emergency department with acute coronary syndrome were evaluated consecutively. A total of 914 patients with non-ST-elevation myocardial infarction who met inclusion criteria were included in the study. The Global Registry of Acute Coronary Events and qSOFA scores were calculated and investigated its contribution to prognostic accuracy by adding cardiac troponin I (cTnI) concentration to the qSOFA score. The threshold value of the investigated prognostic markers was calculated by receiver operating characteristic curve analysis. RESULTS: We found the in-hospital mortality rate to be 3.4%. The area under the receiver operating characteristic curve for Global Registry of Acute Coronary Events and qSOFA-T is 0.840 and 0.826, respectively. CONCLUSION: The qSOFA-T score, which can be calculated easily, quickly, and inexpensively and obtained by adding the cTnI level, had excellent discriminatory power for predicting in-hospital mortality. Difficulty in calculating the Global Registry of Acute Coronary Events score, which requires a computer, can be considered a limitation of this method. Thus, patients with a high qSOFA-T score are at an increased risk of short-term mortality.
Subject(s)
Non-ST Elevated Myocardial Infarction , Sepsis , Humans , Organ Dysfunction Scores , Retrospective Studies , Non-ST Elevated Myocardial Infarction/diagnosis , ROC Curve , Hospital Mortality , Prognosis , Troponin IABSTRACT
A sensitive and selective label-free photoelectrochemical (PEC) immunosensor was designed for the detection of cardiac troponin I (cTnI). The platform was based on a fluorine-doped tin oxide (FTO)-coated glass photoelectrode modified with bismuth vanadate (BiVO4) and sensitized by an electrodeposited bismuth sulfide (Bi2S3) film. The PEC response of the Bi2S3/BiVO4/FTO platform for the ascorbic acid (AA) donor molecule was approximately 1.6-fold higher than the response observed in the absence of Bi2S3. The cTnI antibodies (anti-cTnI) were immobilized on the Bi2S3/BiVO4/FTO platform surface to produce the anti-cTnI/Bi2S3/BiVO4/FTO immunosensor, which was incubated in cTnI solution to inhibit the AA photocurrent. The photocurrent obtained by the proposed immunosensor presented a linear relationship with the logarithm of the cTnI concentration, ranging from 1 pg mL-1 to 1000 ng mL-1. The immunosensor was successfully employed in artificial blood plasma samples for the detection of cTnI, with recovery values ranging from 98.0% to 98.5%.
Subject(s)
Biosensing Techniques , Myocardial Infarction , Humans , Limit of Detection , Electrochemical Techniques , Troponin I , Fluorine , Immunoassay , Electrodes , Myocardial Infarction/diagnosis , BiomarkersABSTRACT
INTRODUCTION: Remote ischemic preconditioning (RIPC) is a new noninvasive myocardial protection strategy that uses blood pressure cuf inflation to simulate transient non-fatal ischemia to protect the myocardium and reduce ischemia-reperfusion injury. Sulfonylureas may mask the effects of RIPC due to their cardioprotec-tive effect. This meta-analysis aimed to evaluate whether RIPC, in the absence of sulfonylureas, reduces troponin release in patients undergoing cardiac surgery. METHODS: We conducted a meta-analysis of randomized controlled clinical trials to determine whether RIPC can reduce postoperative troponin release in cardiac surgery patients undergoing cardiopulmonary bypass without treatment with sulfonylureas. The data were normalized to equivalent units prior to the analysis. A random-effects model was used to provide more conservative estimate of the effects in the presence of known or unknown heterogeneity. RESULTS: Six studies with a total of 570 participants were included. The analysis showed that troponin release was lower in the RIPC group than in the control group at six hours (test of standardized mean differences = 0, Z=3.64, P<0.001) and 48 hours (Z=2.72, P=0.007) postoperatively. When the mean of cross-clamping time was > 60 minutes, RIPC reduced troponin release at six hours (Z=2.84, P=0.005), 24 hours (Z=2.64, P=0.008), and 48 hours (Z=2.87, P=0.004) postoperatively. CONCLUSION: In cardiac surgery patients who are not taking sulfonylureas, RIPC can reduce troponin release at six and 48 hours postoperatively; hence, RIPC may serve significant benefits in certain cardiac surgery patients.
Subject(s)
Cardiac Surgical Procedures , Ischemic Preconditioning , Humans , Cardiac Surgical Procedures/adverse effects , Myocardium , Cardiopulmonary Bypass , Troponin IABSTRACT
OBJECTIVE: Removal of cardiac autoantibodies by immunoadsorption might confer clinical improvement in dilated cardiomyopathy. In this pilot study, we investigated the efficacy and safety of immunoadsorption therapy in refractory heart failure patients with dilated cardiomyopathy. METHODS: This study consisted of 9 heart failure patients with dilated cardiomyopathy, NYHA III-IV, left ventricular ejection fraction <30%, unresponsive to heart failure therapy, and with cardiac autoantibodies. Patients underwent immunoadsorption therapy for five consecutive days using a tryptophan column. Changes in cardiac function (left ventricular ejection fraction, left ventricular end-diastolic diameter, left ventricular end-systolic diameter), exercise capacity (6-minute walk distance), neurohormonal (N-terminal pro-brain natriuretic peptide), proinflammatory (high-sensitive C-reactive protein), and myocardial (cardiac troponin-I), biochemical, and hematological variables were obtained at baseline and after 3 and 6 months of immunoadsorption therapy. RESULTS: Mean left ventricular ejection fraction and 6-minute walk distance significantly increased at 3 months (from 23.27±5.09 to 32.1±1.7%, p=0.01 for left ventricular ejection fraction and from 353±118 to 434±159 m, p=0.04 for 6-minute walk distance) and further increased at 6 months after immunoadsorption therapy (to 34.5±7.7%, p=0.02 for ejection fraction and to 441±136 m, p=0.04 for 6-minute walk distance). NT-proBNP level reduced from 1161(392.8-3034) to 385(116.1-656.5) ng/L (p=0.04), and high-sensitive C-reactive protein decreased from 9.74±0.96 to 4.3±5.8 mg/L (p=0.04) at 6 months. Left ventricular end-diastolic diameter (66.1±5.8 vs. 64.7±8.9 mm) and left ventricular end-systolic diameter (56.1±8.6 vs. 52.3±10.8 mm) tended to decrease but did not reach statistical significance. No significant worsening was observed in creatinine, cardiac troponin-I, and hemoglobin levels after the immunoadsorption procedure. CONCLUSION: In dilated cardiomyopathy patients with refractory heart failure, immunoadsorption may be considered a potentially useful therapeutic option to improve a patient's clinical status.
Subject(s)
Cardiomyopathy, Dilated , Heart Failure , Humans , Stroke Volume , Ventricular Function, Left , Troponin I , C-Reactive Protein , Pilot Projects , AutoantibodiesABSTRACT
Acute myocardial infarction (AMI) as the main cause of death among cardiovascular diseases is defined as a deficiency of oxygen that generates irreversible tissue necrosis in the heart muscle. For diagnostic measurements, the evaluation of cardiac markers concentration like cardiac triponin I (cTnI) in plasma or saliva thought the use of biosensors has become one of the most commonly applied strategies for prognosis of AMI. Inside this diagnostic devices, electrochemical (ECL) ones have been highly encourage to improve sensing capabilities by using different materials and configurations. In this review, the authors presents a summary of studies that involves cTnI detection using ECL biosensors modified with nanomaterials and related mechanisms.
Subject(s)
Myocardial Infarction , Troponin I , Humans , Myocardial Infarction/diagnosis , Biomarkers , Prognosis , MyocardiumABSTRACT
This work reports the construction of a novel nanostructured immunosensor for detection of the troponin I biomarker (cTnI). Anti-troponin I antibody was anchored on the modified graphite electrode with reduced graphene oxide and polytyramine for detection of troponin I in serum samples. The performance of the electro-immunosensor was evaluated by differential pulse voltammetry. The immunosensor presented a wide work range, from 4 ng mL-1 to 4 pg mL-1 , whose detection limit (4 pg mL-1 ) is significantly lower than the basal level in human serum, and maintained 100% of response after 30 days of storage. Moreover, the immunosensor showed good selectivity for detection of cTnI in real sample containing interfering substances and specificity of response to cTnI in the serum of healthy and sick patients, and demonstrated the possibility of reuse for two consecutive analyses, in addition to using a simplified and inexpensive platform when compared to other devices, demonstrating them excellent potential for application in diagnosis in the early stages of acute myocardial infarction.