Effects of blood sample anticoagulants on lateral flow assays using luminescent photon-upconverting and Eu(III) nanoparticle reporters

Many quantitative and semiquantitative lateral flow (LF) assays have been introduced for clinical analytes such as biomarkers for cancer or acute myocardial infarction (AMI). Various detection technologies involving quantitative analyzing devices have been reported to have sufficient analytical sensitivity and quantification capability for clinical point-of-care tests. Fluorescence-based detection technologies such as quantum dots, Eu(III) nanoparticles, and photon-upconverting nanoparticles (UCNPs) have been introduced as promising solutions for point-of-care devices because of their high detectability by optical sensors. Lateral flow assays can be used for various sample types, e.g., urine, saliva, cerebrospinal fluid, and blood. This study focuses on the properties of serum and plasma because of their relevance in cancer and AMI diagnostics. The limit of detection was compared in LF assays having Eu(III) nanoparticles or UCNPs as reporters and the antibody configurations for two different analytes (prostate-specific antigen and cardiac troponin I (cTnI)). The results indicate a significant effect of anticoagulants in venipuncture tubes. The samples in K₃EDTA tubes resulted in significant interference by decreased reporter particle mobility, and thus the limit of detection was up to eightfold less sensitive compared to serum samples. Despite the matrix interference in the cTnI assay with UCNP reporters, limits of detection of 41 ng/L with serum and 66 ng/L with the Li-heparin sample were obtained.     

Ultra‐sensitive,rapid gold nanoparticle‐quantum dot plexcitonic self‐assembled aptamer‐based nanobiosensor for the detection of human cardiac troponin I

Acute myocardial infarction (AMI) is one of the leading causes of death throughout the world. Usual methods for detecting AMI are expensive, time‐consuming and using blood samples as biological samples. Therefore, creating an ultra‐fast, sensitive and non‐invasive diagnostic test is necessary. Herein, a novel ultra‐sensitive, fluorescent, plasmon‐exciton coupling hybrid of a gold nanoparticle‐quantum dot (PQ)‐based aptamer nanobiosensor is presented for the detection of human cardiac troponin I (cTnI), the golden biomarker of AMI, and a preclinical test is performed within saliva. The binding of the cTnI protein to aptamer leads to a fluorescence enhancement of the plexcitonic hybrid system. The response range of this nanobiosensor is 0.4–2500 fM and the limit of detection is 0.3 fM. It seems that this novel design of nanobiosensor in the form of the PQ plexcitonic hybrid system can presents new opportunities for nanobiosensor progress.     

心肌损害标志物的评价及应用策略

根据血清中有关酶（如：天门冬氨酸氨基转移酶(AST)、乳酸脱氢酶(LD)、肌酸激酶及其同工酶(CK-MB)）活性的变化来诊断急性心肌梗塞（AMI）已有多年的历史.近年来,一些蛋白质标志物,如：CK-MB质量,心肌肌红蛋白,心肌肌钙蛋白（cTn）也已逐渐应用于临床诊断.其中心肌肌红蛋白是一项良好的排除心肌梗塞的指标,而心肌肌钙蛋白则是很好的确证指标.CK-MB质量的分析性能高于其活性测定.蛋白质标志物分析还可用于冠心病的危险分级及监测治疗.血清酶分析由于价廉、方法成熟,也不失为有效的AMI辅助诊断指标.需特别注意标本采集时间对结果应用的影响.     

Release patterns of copeptin and troponin in Tako-Tsubo cardiomyopathy

Copeptin, in addition to troponin, has recently been suggested for non-invasive differentiation between Tako-Tsubo cardiomyopathy (TTC) and acute myocardial infarction (AMI). In order to test this hypothesis, we investigated release patterns of pituitary copeptin and cardiac troponin in 49 patients with TTC and 49 age-, gender-, and ECG-matched control patients with AMI. Elevated copeptin levels (i.e. >12 pmol/l) at cardiac catheterization were found in 23/49 (47%) TTC patients and 25/49 (51%) AMI patients. Of these, median copeptin levels were almost identical in both cohorts (34.1 vs. 35.4 pmol/l). Subgroup analysis according to ECG changes revealed that AMI patients with ST-segment elevation had 3.6-fold higher copeptin levels than AMI patients without ST-segment elevation (p<0.05). Furthermore, in patients with TTC and atypical (midventricular) ballooning on left ventricular angiography, copeptin levels were 5.7-fold higher than in TTC patients with a typical (apical) type of ballooning (p<0.01). Elevated troponin T levels (i.e. >0.01 μg/l) at catheterization were detectable in 47/49 (96%) TTC patients and 45/49 (92%) AMI patients; however, peak levels did not differ significantly between both cohorts (median 0.35 vs. 0.27 μg/l). Subgroup analysis according to ECG changes revealed 2-fold higher peak troponin T levels in TTC patients presenting with ST-segment elevation than non-ST-segment elevation (p<0.05). In conclusion, copeptin does not seem to significantly increase non-invasive differentiation between TTC and AMI. At present, coronary angiography, specifically in patients with ST-segment elevation at presentation remains absolutely mandatory.     

Diagnosis of myocardial infarction: integration of serum markers and clinical descriptors using information theory

OBJECTIVE: We examine the use of information theory applied to a single cardiac troponin T (cTnT) (first generation monoclonal; Boehringer Mannheim Corp., Indianapolis, Indiana) used with the character of chest pain, electrocardiography (ECG) and serial ECG changes in the evaluation of acute myocardial infarction (AMI). We combined a single measure of cTnT (blinded to the investigators) with a creatine kinase MB isoenzyme (CK-MB) measurement to discover the best decision value for this test in a study of 293 consecutive patients presenting to the emergency department with symptoms warranting exclusion of AMI. METHODS: The decision value for determining whether cTnT is positive or negative was determined independently of the final diagnosis by examining the information in the cTnT and CKMB data. Using information theory, an autocorrelation matrix with a one-to-one pairing of the CKMB and troponin T was constructed. The effective information, also known as Kullback entropy, assigned the values for troponin T and for CKMB that have the lowest frequency of misclassification error. The Kullback entropy is determined by subtracting the data entropy from the maximum entropy of the data set in which the information has been destroyed. The assignment of the optimum decision values was made independently of the clinical diagnoses without the construction of a receiver-operator characteristic curve (ROC). The final diagnosis of AMI was independently determined by the clinicians and entered into the medical record. RESULTS: The decision value for cTnT was 0.1 ng/ml as determined by the the information in the data. The method was validated within the same study by mapping the results so obtained into the diagnoses obtained independently by the clinicians using all of the methods at their disposal. The cTnT was different in AMI (n = 60) compared with non-AMI patients (n = 233) (2.08 +/- 0.21 vs. 0.07 +/- 0.10; p < .0001). CONCLUSION: Information theory provides a strong framework and methodology for determining the decision value for cTnT which minimizes misclassification errors at 0.1 ng/ml. The result has a strong correlation with other features in detecting AMI in patients presenting with chest pain.     

Predictive value of circulating miR-328 and miR-134 for acute myocardial infarction

MicroRNA (miRNAs) is demonstrated to be present in the blood of humans and has been increasingly suggested as a novel biomarker for various pathological processes in the heart, including myocardial infarction, myocardial remodeling and progression to heart failure. In this study, we aim to evaluate the diagnostic and prognostic value of circulating miR-328 and miR-134 in patients with acute myocardial infarction (AMI). Circulating levels of miR-328 and miR-134 were detected by quantitative real-time PCR in plasma samples from 359 AMI patients and 30 healthy volunteers. Concentrations of high-sensitivity cardiac troponin T (hs-cTnT) were measured using electrochemiluminescence-based methods. MiRNAs were assessed for discrimination of a clinical diagnosis of AMI and for association with primary clinical endpoint defined as a composite of cardiogenic death and development of heart failure within 6 months after infarction. Results showed that levels of plasma miR-328 and miR-134 were significantly higher in AMI patients than in healthy controls. Receiver operating characteristic curve analyses showed significant diagnostic value of miR-328 and miR-134 for AMI. However, neither of them was superior to hs-cTnT for the diagnosis. Additionally, increased miRNA levels were strongly associated with increased risk of mortality or heart failure within 6 months for miR-328 (OR 7.35, 95 % confidence interval 1.07–17.83, P < 0.001) and miR-134 (OR 2.28, 95 % confidence interval 1.03–11.32 P < 0.001). In conclusion, circulating miR-328 and miR-134 could be potential indicators for AMI, and the miRNA levels are associated with increased risk of mortality or development of heart failure.     

Electrophoresis of serum isoenzymes and proteins following acute myocardial infarction

The clinical significance of the serum enzymes creatine kinase (CK, EC 2.7.3.2), lactate dehydrogenase (LD, EC 1.1.1.27) and aspartate aminotransferase (EC 2.6.1.1), and the isoenzymes CK 1–3 and LD 1–5, in acute myocardial infarction (AMI) is reviewed. Particular attention is given to electrophoretic analysis of the isoenzymes (and the CK isoforms/subforms) following AMI and thrombolytic therapy. Other protein markers for the monitoring of AMI, including myoglobin and muscle contractile proteins, are also discussed and the potential for the detection of new marker proteins using high-resolution two-dimensional electrophoretic methods is demonstrated. Whilst emphasis is placed upon electrophoretic methods the value of complementary immunoassays is acknowledged in order to maintain a balanced perspective.     

Implications of troponin testing in clinical medicine

During the past decade considerable research has been conducted into the use of cardiac troponins, their diagnostic capability and their potential to allow risk stratification in patients with acute chest pain. Determination of risk in patients with suspected myocardial ischaemia is known to be as important as retrospective confirmation of a diagnosis of myocardial infarction (MI). Therefore, creatine kinase (CK)-MB - the former 'gold standard' in detecting myocardial necrosis - has been supplanted by new, more accurate biomarkers.Measurement of cardiac troponin levels constitute a substantial determinant in assessment of ischaemic heart disease, the presentations of which range from silent ischaemia to acute MI. Under these conditions, troponin release is regarded as surrogate marker of thrombus formation and peripheral embolization, and therefore new therapeutic strategies are focusing on potent antithrombotic regimens to improve long-term outcomes. Although elevated troponin levels are highly sensitive and specific indicators of myocardial damage, they are not always reflective of acute ischaemic coronary artery disease; other processes have been identified that cause elevations in these biomarkers. However, because prognosis appears to be related to the presence of troponins regardless of the mechanism of myocardial damage, clinicians increasingly rely on troponin assays when formulating individual therapeutic plans.     

Elevated cardiac troponin T indicating myocardial infarction or myocarditis–urgent cardiac catheter examination–or do we have to consider other reasons?

Alveolar rhabdomyosarcoma is an aggressive tumour in adulthood, in which cardiac troponin T seems to be a tumour marker and course parameter. We present the clinical course of a young man suffering from this rare disease and the development of troponin T during therapy. Noninvasive cardiac imaging was used to exclude cardiac involvement, myocardial infarction or inflammation processes.     

Identification of Cardiac Myosin-binding Protein C as a Candidate Biomarker of Myocardial Infarction by Proteomics Analysis

Acute myocardial infarction (AMI) is a common cause of death for which effective treatments are available provided that diagnosis is rapid. The current diagnostic gold standards are circulating cardiac troponins I and T. However, their slow release delays diagnosis, and their persistence limits their utility in the identification of reinfarction. The aim was to identify candidate biomarkers of AMI. Isolated mouse hearts were perfused with oxygenated protein-free buffer, and coronary effluent was collected after ischemia or during matched normoxic perfusion. Effluents were analyzed using proteomics approaches based on one- or two-dimensional initial separation. Of the 459 proteins identified after ischemia with one-dimensional separation, 320 were not detected in the control coronary effluent. Among these were all classic existing biomarkers of AMI. We also identified the cardiac isoform of myosin-binding protein C in its full-length form and as a 40-kDa degradation product. This protein was not detected in the other murine organs examined, increased markedly with even trivial myocardial infarction, and could be detected in the plasma after myocardial infarction in vivo, a profile compatible with a biomarker of AMI. Two-dimensional fluorescence DIGE of ischemic and control coronary effluents identified more than 200 asymmetric spots verified by swapping dyes. Once again existing biomarkers of injury were confirmed as well as posttranslational modifications of antioxidant proteins such as peroxiredoxins. Perfusing hearts with protein-free buffers provides a platform of graded ischemic injury that allows detailed analysis of protein release and identification of candidate cardiac biomarkers like myosin-binding protein C.Acute myocardial infarction (AMI)1 is a common cause of death for which effective treatments are available provided that the condition is rapidly diagnosed. The modern diagnosis of AMI relies on the rise and fall of a specific serum biomarker accompanied by an appropriate circumstance such as chest pain or revascularization. In this accepted paradigm, the diagnosis cannot be ruled in or ruled out without the definite presence or definite absence of a serum biomarker. The ideal biomarker of cardiac injury should be cardiac specific and released rapidly after myocardial injury in direct proportion to the extent of damage. Furthermore, the biomarker should have a high sensitivity and specificity (1). Several biomarkers of AMI have been described in the literature, but only a few, none of which are ideal, have found their way into routine clinical practice. For example, CK-MB starts to increase 4–8 h after coronary artery occlusion and returns to base line within 2–3 days (2). However, its use is limited by its presence in skeletal muscle and normal serum and by sensitivity of the assay to interference, causing some to question its utility (3). Myoglobin is another cytoplasmic protein found in cardiac and skeletal, but not smooth, muscle. It is released even earlier within 1–2 h of AMI and peaks within 5–6 h (2). Unfortunately, any injury to skeletal muscle also causes elevated levels of myoglobin, reducing specificity. Fatty acid-binding proteins (FABPs) are small (15-kDa) cytoplasmic proteins expressed in all tissues with active fatty acid metabolism. Among the nine proteins, heart-specific FABP (H-FABP) is found in heart but also kidney, brain, skeletal muscle, and placenta (4). Following acute myocardial infarction, H-FABP can be detected within 20 min and peaks at 4 h, considerably faster even than CK/CK-MB in the same patient cohort. Although H-FABP concentrations in normal plasma are low, they are known to rise nonspecifically during physical exertion (without a troponin rise), kidney injury, and stroke (5).The most specific and sensitive cardiac proteins released after acute myocardial infarction are cardiac troponins I and T. Both troponins I and T are released slowly, peaking ∼18 h after myocardial infarction, and remain elevated for 7–10 days (2). This slow release is likely the result of their relatively inaccessible cellular location compared with CK-MB, myoglobin, and H-FABP. Troponins regulate the physical interaction of actin and myosin and thus are found almost entirely associated within the crystalline structure of the sarcomere of striated muscle cells (6). The troponin complex is composed of three forms: I, T, and C. Troponins I and T exist as cardiac specific isoforms with epitopes that differ from the corresponding skeletal isoforms. In addition, the absent or extremely low normal circulating levels of troponin provide the greatest dynamic range of any of the currently available biomarkers (7). Although there is no doubt troponins have revolutionized the detection and management of patients with AMI (8), they do have disadvantages. The slow release of troponin delays diagnosis and the initiation of specific treatments that could salvage heart tissue in those in whom it is raised. Similarly, patients in whom it is absent and who are ultimately reassured and discharged are admitted to the hospital unnecessarily. Furthermore, the persistence of troponins limits their utility in the diagnosis of reinfarction.It is therefore widely accepted that there is a need for new biomarkers that can diagnose AMI earlier during its natural history and/or that have a short plasma half-life, allowing use in diagnosis and quantification of reinfarction. The purpose of this study was to use the platform of the crystalloid perfused mouse hearts to perform a systematic proteomics analysis of the coronary effluent after minimal AMI to identify new potential biomarkers (9).     

Optical immunosensor using carbon nanotubes coated with a photovoltaic polymer

In this work, an on-chip optical immunosensor using an individually assembled carbon nanotube (CNT) coated with a photovoltaic polymer has been proposed, developed, characterized, and applied for the detection of cardiac biomarkers. An individual CNT was self-assembled on a nickel (Ni)-patterned electrode by magnetically attracting the residual iron catalyst at one end of the CNT. After the CNT self-assembled electrode was prepared, it was coated with a photovoltaic polymer to implement a CNT photodetector. Under an incident light, the photovoltaic polymer generated electrons that changed the conductivity of the CNT. The CNT photodetector was finally insulated with parylene to prevent interruptions of charged molecules in a sample solution, such as non-specifically bound proteins and various ions. Chemiluminescent immunoassay was directly performed on the CNT photodetector for an on-chip detection of cardiac troponin T (cTnT) with a detection limit of 12 pg/mL. High sensitivity and reliable selectivity have been achieved through the use of on-chip measurement of chemiluminescent light by the CNT photodetector. As a result, the developed device is envisaged as a new platform for optical immunosensing using the individually self-assembled CNT for point-of-care (POC) clinical diagnostics.     

Plasma intermedin levels in patients with acute myocardial infarction

It has been shown that adrenomedullin (ADM) may function as a cardiovascular-regulatory peptide in humans. Intermedin (IMD) is a newly discovered peptide related to ADM and has a greater range of biological effects on the cardiovascular in animal experiments. The purpose of the study was to investigate the pathophysiological role of IMD in patients with acute myocardial infarction (AMI). The present study included twenty patients with acute ST-segment elevation myocardial infarction (STEMI), thirty-three with stable coronary heart disease (SCHD), and eighteen healthy controls. Plasma levels of IMD, malonaldehyde (MDA), and superoxide dismutase (SOD) and cardiac biomarkers were determined at one, two, four and seven days following AMI. Plasma IMD levels were significantly increased on day 1 in AMI patients when compared with SCHD subjects (P = 0.014), and reached a peak of 181.88 ± 9.47 pg/ml at 96 h. Plasma IMD concentrations were correlated with MDA and SOD. Furthermore, patients with severe lesions in their coronary arteries tended to have higher plasma IMD levels (P < 0.05) in AMI patients. A significant increase in plasma IMD following AMI may be associated with oxidative stress, and could be used as a marker to reflect the severity of the coronary stenosis.     

应用高敏感性肌钙蛋白T检测冠心病的临床意义初探

目的：探讨应用高敏感性肌钙蛋白T检测冠心病的临床意义。方法：2010年8月到2013年1月选择来我院治疗的126例冠心冠心病患者者作为观察组,同期选择在我院体检的健康人126例作为对照组,对血清高敏感性肌钙蛋白T、普通肌钙蛋白T与肌酸肌酶同工酶进行检测。结果：两组在4小时与12小时的高敏感性肌钙蛋白T、普通肌钙蛋白T与肌酸肌酶同工酶检测结果组间对比有明显差异（P〈0．05）。而在2小时,只有高敏感性肌钙蛋白T在组间对比有明显差异（P〈0．05）。同时观察组高敏感性肌钙蛋白的阴性检出率明显高于普通肌钙蛋白T与肌酸肌酶同工酶（P〈0．05）。而阳性检出率也同样高于前两者,但是无统计学差异（P〉0．05）。结论：高敏感性肌钙蛋白T检测技术的出现为冠心病的检测与心肌损伤的防治带来了有效的方法,在临床检测中可以作为心肌损伤的一个重要的标志。     

心肌型脂肪酸结合蛋白胶体金检测试纸条的制备和初步应用

目的应用胶体金免疫层析法制备检测全血或血清样本中心肌型脂肪酸结合蛋白（H-FABP）的检测试纸条,用于急性心肌梗塞（AMI）的早期辅助诊断。方法采用柠檬酸三钠还原法制备胶体金,标记鼠抗心肌型脂肪酸结合蛋白单克隆抗体,喷于玻璃纤维膜上制成胶体金结合物垫,将另一株鼠抗心肌型脂肪酸结合蛋白单克隆抗体和抗鼠二抗分别包被检测线和质控线,组装成试纸条进行灵敏性、特异性、精密性、稳定性及临床样品检测。结果该试纸条的检测灵敏度为10ng／mL,15min内可判定结果;与肌钙蛋白I、C反应蛋白、肌酸激酶、人心肌肌红蛋白无交叉反应。检测240份临床标本,与临床诊断结果进行配对分析,阳性符合率95．83％、阴性符合率100％、总符合率97．92％。结论制备的H-FABP检测试纸条有良好的灵敏性、特异性,可用于早期AMI的辅助诊断。     

Development of a surface plasmon resonance-based immunosensor for the rapid detection of cardiac troponin I

The concentration of cardiac troponin I (cTnI) in blood is an important marker for heart muscle cell damage. A surface plasmon resonance (SPR)-based immunosensor was devised for the rapid and specific detection of cTnI. It was constructed by crosslinking a monoclonal antibody P-II-13, which was generated against a loop region (aa 84–94) of cTnI protein as an epitope peptide, onto a chemically modified thin gold film. The performance of the sensor was examined with respect to the SPR signal intensity versus cTnI concentration. The signal intensity was directly correlated with the cTnI concentration in the range of 0–160 μg/l. The sensor signal was saturated when the concentration of cTnI approached 660 μg/l with the SPR intensity of 172 RU. The lower detection limit of the sensor was 68 ng/l cTnI, which was comparable to ELISA-based commercial cTnI detection systems.     

High sensitivity cardiac troponin T in patients not having an acute coronary syndrome: results from the TRAPID-AMI study

Purpose: To describe the baseline, 1?hr and delta high sensitivity cardiac troponin (hs-cTnT) values in patients with suspected acute myocardial infarction (AMI) but without a final acute coronary syndrome (ACS) diagnosis.

Materials and methods: hs-cTnT assay for RAPID rule out of acute myocardial infarction (TRAPID-AMI) was a prospective diagnostic trial that enrolled emergency department (ED) patients with suspected AMI. Final patient diagnoses were adjudicated by a clinical events committee and subjects placed in different clinical groups: AMI, unstable angina, non-ACS cardiac, non-cardiac and unknown origin. The baseline, 1?hr and delta hs-cTnT values were analysed in the 902 non-ACS patients.

Results: Amongst the 1282 studied the patient groups were 213 (17%) AMI, 167 (13%) unstable angina, 113 (9%) non-ACS cardiac, 288 (22%) non-cardiac and 501 (39%) unknown origin. The hs-cTnT values in the non-cardiac and unknown origin groups were combined. The median hs-cTnT values (ng/L) were higher (p?<?0.001) in the non-ACS cardiac compared to the non-cardiac/unknown origin group at baseline (11.8,?<5) and 1?hr (12.3,?<5). Their negative predictive values were 0.955 (baseline) and 0.954 (1?hr) for predicting non-ACS cardiac versus non-cardiac/unknown origin diagnoses.

Conclusions: Hs-cTnT may help predict whether non-ACS ED patients have a final non-ACS cardiac or non-cardiac/unknown origin diagnoses.     

Clinical and analytical performance of automated immunochemiluminometric assays for determination of cardiac markers in serum

Three new immunochemiluminometric assays for quantitation of cardiac markers, i.e. creatine kinase isoenzyme MB (CK-MB), myoglobin and cardiac troponin I (cTnI), were evaluated with the Sanofi Access analyser. The complete profile requires 20 min to perform, the method being suitable in true stat situations. In patients with early myocardial infarction (median time of sample collection: 210 min from onset, range 30–450; n = 44), the diagnostic sensitivity of Access cTnI was 66%, compared with 80% for myoglobin, and 43% for CK-MB. For comparison, cTnI, with an automated immunofluorimetric assay was also measured (sensitivity, 45%; p < 0.05 vs. Access cTnI). Our data confirmed myoglobin as the first biochemical marker to appear elevated after infarction. However, cTnI may be a more sensitive marker for early detection of cardiac damage than initially thought, when determined by an ultrasensitive method such as an immunochemiluminometric assay. © 1998 John Wiley & Sons, Ltd.     

The protective effect of peony extract on acute myocardial infarction in rats

To investigate the protective effects, and the mechanisms involved, of an extract of the medicinal herb radix paeoniae rubra (PE) on cardiovascular disease, acute myocardial infarction (AMI) was induced by ligation of the left coronary artery in Sprague Dawley rats. Animals were randomly divided into six groups: control, sham-operated, AMI, AMI + PE low dose, AMI + PE high dose, and AMI + positive control. Myocardial enzymes, cytokines, oxidative stress, blood coagulation times, a marker for early stage apoptosis, caspase-3 activity, and expression levels of bax, bcl-2 and fas in isolated primary cardiomyocytes were examined. In contrast with control and sham groups, significant increases in the following parameters were measured in the blood of AMI group animals: activities of cardiac enzymes including glutamic oxaloacetic transaminase, creatine kinase, creatine kinase-MB, lactate dehydrogenase, α-hydroxybutyric dehydrogenase, and levels of IL-10, TNFα, and lipid peroxidation. Under the same conditions, superoxide dismutase activity, thrombin time and activated partial thromboplastin time decreased significantly. PE showed a dose-dependent protection against AMI-induced alterations in cardiac enzymes, cytokines, oxidative stress, and coagulation. In AMI cardiomyocytes, compared with control and sham groups, the left ventricular end-diastolic pressure, early stage apoptosis, caspase-3 activity and expression levels of bax, bcl-2 and fas significantly increased, while the ratio bcl-2/bax decreased. PE showed dose-dependent protection. These results suggest that PE is an effective agent for protecting against AMI; possible mechanisms may include the regulation of cardiac enzymes, cytokines, oxidative stress, coagulation and apoptosis.     

Trends in Cardiac Biomarker Testing in China for Patients with Acute Myocardial Infarction, 2001 to 2011: China PEACE-Retrospective AMI Study

Objectives

To describe trends in the availability of biomarker testing in Chinese hospitals and how practice complies with established standards for the diagnosis of acute myocardial infarction (AMI).

Background

Cardiac biomarker testing is standard in high-income countries, but little is known about the availability and use of cardiac biomarker testing in low- and middle-income countries (LMICs) such as China.

Methods

Based on a nationally representative sample of Chinese hospitals in 2001, 2006 and 2011, we describe the temporal trends and regional differences in the hospital capability and rates of use of cardiac biomarker testing, as well as the variation in use across hospitals with testing capability, for patients labeled with the diagnosis of AMI.

Results

We sampled 175 hospitals (162 participated in the study) and 18,631 AMI admissions. 14,370 patients were included in analysis of biomarker use. The proportion of hospitals with biomarker testing capability was 57.4% in 2001 (25.0% troponin and 32.4% creatine kinase MB fraction (CK-MB) only) and 96.3% (81.4% troponin and 14.9% CK-MB only) in 2011. The proportion of hospitals with troponin testing capability in 2011 was significantly higher in urban compared with rural hospitals (96.8% vs. 71.4%, p< 0.001). In 2011, only 55.9% of hospitals with troponin testing capability (71 out of 127 hospitals) used the assay for more than 80% of their patients with AMI. Among hospitals with either biomarker testing capability, there was marked variation in use in both rural (from 7.1% to 100.0% of patients) and urban hospitals (from 57.9% to 100.0% of patients). In 2011, 36.1% of the patients with AMI did not have troponin tested and 4.9% did not have either biomarker measured.

Conclusions

The recommended biomarker tests for AMI diagnosis are not universally available and the testing is not consistently applied when it is available in China.

Trial Registration

ClinicalTrials.gov NCT01624883     

An o-aminobenzoic acid film-based immunoelectrode for detection of the cardiac troponin T in human serum

An amperometric immunosensor for cardiac troponin T detection in human serum troponin T, a marker considered as “gold standard” for acute myocardial infarction diagnosis, is described. A stable carboxylic film to covalently bind antibodies against cTnT onto electrode surface was achieved with electropolymerization of the o-aminobenzoic acid. A fractional factorial study was performed to optimize the electropolymerization parameters. Cyclic voltammetry assays were carried out for characterize steps of the modified electrode surface. The obtained calibration curve at −0.05 V by amperometry presented a good linear response range from 0.05 to 5.0 ng mL⁻¹ cTnT with a correlation coefficient of 0.992 (n = 6) and 0.016 ng mL⁻¹ detection limit. The electrodes showed a good stability upon the analytical responses retaining 91.6% of its initial response after 18 days. This sensor showed outgoing results regarding sensitivity allowing reliable measurements of the cTnT at levels of clinical significance for acute myocardial infarctions diagnosis.