cTnI Concentrations Research Articles

Evaluation of cardiac troponin I as a predictor of death in critically ill cats.

Abnormally high serum cardiac troponin I (cTnI) concentration, reflecting leakage from or necrosis of cardiomyocytes, is a negative prognosticator for death in dogs. To investigate in critically ill cats whether serum cTnI concentration is abnormally high, identify conditions associated with abnormally high cTnI concentrations, and evaluate cTnI as an independent prognosticator for death and a potential coprognosticator to the acute patient physiologic and laboratory evaluation (APPLE) score in cats. One hundred nineteen cats admitted to intensive care units (ICU) and 13 healthy cats at 2 university teaching hospitals. Prospective study. Clinical examinations were performed, APPLE scores calculated, and serum cTnI and serum amyloid A (SAA) measured within 24 hours after admission. Outcome was defined as death/euthanasia or survival to discharge, 28 and 90 days after ICU-admission. Prognostic capacity of cTnI, APPLE scores and models combining cTnI and scores were evaluated by receiver-operator-characteristic analyses. Median (IQR) serum cTnI concentration was higher in ill (0.63 [0.18-2.65] ng/mL) compared to healthy (0.015 [0.005-0.041] ng/mL) cats (P < .001) and higher in subgroups with structural cardiac disease (2.05 [0.54-16.59] ng/mL; P < .001) or SAA >5mg/L (0.84 [0.23-2.81] ng/mL; P=.009) than in cats without these characteristics (0.45 [0.12-1.70] and 0.35 [0.015-0.96] ng/mL). The in-hospital case fatality rate was 29%. Neither serum cTnI concentration for all critically ill cats (area-under-the-curve 0.567 [95% CI 0.454-0.680], n=119) or subgroups (0.625 [0.387-0.863], n=27; 0.506 [0.360-0.652], n=86), nor APPLE scores (fast 0.568 [0.453-0.682], full 0.585 [0.470-0.699], n=100), were significant prognosticators for death. Abnormally high serum cTnI concentration was common in critically ill cats. Unlike in dogs, cTnI did not confer prognostic information regarding death.

EVALUATION OF PLASMA CARDIAC TROPONIN I IN ASIAN ELEPHANTS (ELEPHAS MAXIMUS) USING TWO CLINICAL ANALYZERS.

Cardiac troponin I (cTnI) is specific to myocardial tissue, highly conserved across taxa, and a reliable indicator of myocardial disease in human and veterinary medicine. Biomarkers, like cTnI, may be useful for cardiac evaluation of elephants because the application of other modalities is complicated by the size of the animal. The goal of this study was to establish observed ranges for plasma cTnI in Asian elephants (Elephas maximus) measured by two point-of-care analyzers. Blood was collected from captive juvenile (≤15 yr; n = 9), adult (16-50 yr; n = 42), and geriatric (>50 yr; n = 16) elephants. Following centrifugation, heparinized plasma was stored at 5°C prior to and in between analyses on iSTAT (Abbott Point of Care Inc, Princeton, NJ 08540, USA) and HUBI-QUANpro (Humiasis Co, Ltd, Anyang-si 14042, South Korea) analyzers. With the exception of two results, plasma concentrations of cTnI were below the limit of quantification (LOQ < 0.05 ng/ml) for the HUBI-QUANpro (n = 64), which prohibited comparison between the two analyzers. Observed ranges were determined for plasma cTnI concentrations reported by the iSTAT for the entire population sampled (n = 58; mean 0.011 ng/ml; SD ± 0.013 ng/ml; range 0.00-0.07 ng/ml; 95% CI 0.008-0.015 ng/ml; median 0.01 ng/ml) and with outliers excluded (n = 50; mean 0.007 ng/ml; SD ± 0.007 ng/ml; range 0.00-0.02 ng/ml; 95% CI 0.005-0.009 ng/ml; median 0.01 ng/ml). No significant differences were observed between age classes (P = 0.70) or sexes (P = 0.34). Higher cTnI concentrations were significantly correlated with increasing age (Pearson's r = 0.426; P = 0.002). Future studies are warranted to investigate the diagnostic potential of plasma cTnI in Asian elephants.

Shenxiong glucose injection inhibits oxidative stress and apoptosis to ameliorate isoproterenol-induced myocardial ischemia in rats and improve the function of HUVECs exposed to CoCl2.

Background: Shenxiong Glucose Injection (SGI) is a traditional Chinese medicine formula composed of ligustrazine hydrochloride and Danshen (Radix et rhizoma Salviae miltiorrhizae; Salvia miltiorrhiza Bunge, Lamiaceae). Our previous studies and others have shown that SGI has excellent therapeutic effects on myocardial ischemia (MI). However, the potential mechanisms of action have yet to be elucidated. This study aimed to explore the molecular mechanism of SGI in MI treatment. Methods: Sprague-Dawley rats were treated with isoproterenol (ISO) to establish the MI model. Electrocardiograms, hemodynamic parameters, echocardiograms, reactive oxygen species (ROS) levels, and serum concentrations of cardiac troponin I (cTnI) and cardiac troponin T (cTnT) were analyzed to explore the protective effect of SGI on MI. In addition, a model of oxidative damage and apoptosis in human umbilical vein endothelial cells (HUVECs) was established using CoCl2. Cell viability, Ca2+ concentration, mitochondrial membrane potential (MMP), apoptosis, intracellular ROS, and cell cycle parameters were detected in the HUVEC model. The expression of apoptosis-related proteins (Bcl-2, Caspase-3, PARP, cytoplasmic and mitochondrial Cyt-c and Bax, and p-ERK1/2) was determined by western blotting, and the expression of cleaved caspase-3 was analyzed by immunofluorescence. Results: SGI significantly reduced ROS production and serum concentrations of cTnI and cTnT, reversed ST-segment elevation, and attenuated the deterioration of left ventricular function in ISO-induced MI rats. In vitro, SGI treatment significantly inhibited intracellular ROS overexpression, Ca2+ influx, MMP disruption, and G2/M arrest in the cell cycle. Additionally, SGI treatment markedly upregulated the expression of anti-apoptotic protein Bcl-2 and downregulated the expression of pro-apoptotic proteins p-ERK1/2, mitochondrial Bax, cytoplasmic Cyt-c, cleaved caspase-3, and PARP. Conclusion: SGI could improve MI by inhibiting the oxidative stress and apoptosis signaling pathways. These findings provide evidence to explain the pharmacological action and underlying molecular mechanisms of SGI in the treatment of MI.

Rapid diagnosis of acute myocardial infarction based on reverse transcription-accelerated strand exchange amplification of miR-208a.

Acute myocardial infarction (AMI) is a prevalent cardiovascular disease associated with high morbidity and mortality, posing a significant threat to human health. Therefore, early diagnosis of AMI has become a focal point of research. MiR-208 is specifically expressed in the heart and is involved in the regulation of cardiomyocyte hypertrophy, cardiac fibrosis, and other myocardial gene expressions. It is expected to be applied in the clinical detection of AMI due to its release by damaged myocardial cells within 3 hours of AMI. In this study, we developed a denatured bubble-mediated reverse transcription-accelerated strand exchange amplification (RT-ASEA) method to detect the early biomarker miR-208a of AMI. The novel approach allowed rapid amplification of miR-208a in 15 minutes, with good performance in terms of repeatability (CV < 6%), determination limit (1 × 100 pmol L-1), and linearity (R2 = 0.9690). Based on the analysis of 42 clinical samples, a strong correlation was observed between the Ct value of miR-208a detected by the RT-ASEA method and the cTnI concentration, considered the gold standard for diagnosis of AMI. The research suggested that the RT-ASEA method could be applied to distinguish between AMI and healthy groups. The area under the receiver operating characteristic curve (AUC) was 0.9976, with a sensitivity of 96% and a specificity of 100%. Optimized RT-ASEA is a reliable and efficient method for miRNA detection. Furthermore, this study provides crucial data support for the development of miR-208a as an early biomarker for AMI, which is of great significance in life and health.

A digital multimeter-based portable photoelectrochemical immunoassay for the detection of cardiac troponin I with enzymatic biocatalytic precipitation.

Early diagnosis of acute myocardial infarction (AMI) can significantly reduce mortality, which can be achieved by the highly sensitive detection of AMI-specific cardiac troponin I (cTnI) biomarkers. Herein a highly sensitive and portable photoelectrochemical (PEC) immunoassay for the detection of cTnI was innovatively fabricated based on an efficient photocurrent response of Cu2O coupling with a split-type enzymatic biocatalytic precipitation reaction with a digital multimeter readout. Initially, Cu2O cubic nanomaterials with a good photocurrent response were obtained by facile green room temperature synthesis and dropped on fluorine-doped tin oxide (FTO) plates as photoactive materials (Cu2O/FTO). In the presence of target cTnI, horseradish peroxidase (HRP) on the detection antibody catalyzes the substrate 4-chloro1-naphthol (4-CN) to produce insoluble precipitates of benzo-4-chlorohexadienone (4-CD) on Cu2O/FTO with the assistance of H2O2, resulting in a decrease in the photocurrent of the Cu2O/FTO electrode. To make the whole inspection process more concise and efficient, we used a flashlight and a digital multimeter as the excitation light source and reading device for the PEC sensing system, respectively. Under the optimal conditions of immunoreaction time, pH, and loading, the photocurrent of Cu2O/FTO decreased with increasing target cTnI concentration with a limit of detection (LOD) of 4.7 pg mL-1 in the operating range of 0.01-10 ng mL-1. It is of interest that the developed portable PEC immunoassay is also capable of detecting cTnI in human serum samples with acceptable accuracy compared to the reference cTnI enzyme-linked immunosorbent assay (ELISA) method while maintaining portability and sensitivity.

Label-Free, Portable, and Color-Indicating Cholesteric Liquid Crystal Test Kit for Acute Myocardial Infarction by Spectral Analysis and Naked-Eye Observation

The early diagnosis of acute myocardial infarction is difficult in patients with nondiagnostic characteristics. Acute myocardial infarction with chest pain is associated with increased mortality. This study developed a portable test kit based on cholesteric liquid crystals (CLCs) for the rapid detection of AMI through eye observation at home. The test kit was established on dimethyloctadecyl[3-(trimethoxysilyl)propyl]ammonium chloride-coated substrates covered by a CLC-binding antibody. Cardiac troponin I (cTnI) is a major biomarker of myocardial cellular injury in human blood. The data showed that the concentration of cTnI was related to light transmittance in a positive way. The proposed CLC test kit can be operated with a smartphone; therefore, it has high potential for use as a point-of-care device for home testing. Moreover, the CLC test kit is an effective and innovative device for the rapid testing of acute myocardial infarction-related diseases through eye observation, spectrometer, or even smartphone applications.

Template Free Anisotropically Grown Gold Nanocluster Based Electrochemical Immunosensor for Ultralow Detection of Cardiac Troponin I.

Anisotropic gold nanostructures have fascinated with their exceptional electronic properties, henceforth exploited for the fabrication of electrochemical sensors. However, their synthesis approaches are tedious and often require a growth template. Modern lifestyle has caused an upsurge in the risk of heart attack and requires urgent medical attention. Cardiac troponin I can serve as a biomarker in identification of suspected myocardial infection (heart attack). Hence the present work demonstrates the fabrication of a sensing platform developed by assimilating anisotropic gold nanoclusters (AuNCs) with anti cTnI antibody (acTnI) for the detection of cardiac troponin I (cTnI). The uniqueness and ease of synthesis by a template-free approach provides an extra edge for the fabrication of AuNC coated electrodes. The template-free growth of anisotropic AuNCs onto the indium tin oxide (ITO) glass substrates offers high sensitivity (2.2 × 10-4 A ng-1 mL cm-2) to the developed sensor. The immunosensor was validated by spiking different concentrations of cTnI in artificial serum with negligible interference under optimized conditions. The sensor shows a wide range of detection from 0.06-100 ng/mL with an ultralow detection limit. Thus, it suggests that the template-free immunosensor can potentially be used to screen the traces of cTnI present in blood serum samples, and the AuNCs based platform holds great promise as a transduction matrix, hence it can be exploited for broader sensing applications.

Influence of Dexmedetomidine on Myocardial Injury in Patients with Simultaneous Pancreas-Kidney Transplantation.

Diabetes is one of the most common chronic diseases in the world. End-stage renal disease (ESRD) caused by diabetes is the most serious long-term complication. The main cause of death in patients with simultaneous pancreas-kidney transplantation (SPKT) is cardiovascular disease. Although dexmedetomidine (Dex) has unique advantages in heart protection against ischaemic/reperfusion injury, few clinical studies have been conducted on its cardioprotective effect in SPKT. This study aimed to explore the influence of Dex on myocardial injury in patients undergoing SPKT and to analyze its possible mechanism. A randomized controlled trial (RCT) was performed from July 1, 2018 to December 1, 2020. Eighty patients, regardless of gender, scheduled for SPKT were randomly allocated into a Dex group (D group) receiving Dex at a rate of 1 µg/kg for 10 minutes before anaesthesia induction and then continuous infusion at 0.5 µg/kg/hour until the end of surgery and control group (C group) receiving equivalent capacity of saline. Serum cardiac troponin I (cTnI), creatine kinase isoenzyme (CK-MB), tumour necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were recorded at 5 minutes after anaesthesia induction (baseline,T0), 5 minutes before renal arteriovenous opening (T1), 30 minutes after renal arteriovenous opening (T2), 30 minutes after pancreatic related arteriovenous opening (T3), immediately after surgery (T4), 4 hours after surgery (T5), and 24 hours after surgery (T6). Adverse cardiovascular events were recorded during the perioperative period. Changes in ECG S-T segments and T waves were monitored at T0-T6. Myocardial infarction and percutaneous coronary intervention were recorded with an average follow-up of one year. Compared with T0, TNF-α and IL-6 concentrations significantly increased at T1-T6 in the C and D groups (P < 0.05). IL-6 concentration increased significantly after renal artery opening and reached the peak after the opening of pancreatic blood vessels. Compared with the C group, TNF-α, and IL-6 concentrations were significantly reduced in group D at T2-T6 (P < 0.05). Compared with T0, cTnI and CK-MB concentrations were significantly increased at T3-T6 in the C and D groups (P < 0.05). cTnI and CK-MB concentrations increased significantly after the opening of renal artery, and reached the peak after the opening of pancreatic blood vessels. Compared with the C group, cTnI and CK-MB concentrations were significantly reduced in the D group at T3-T6 (P < 0.05). There was no significant difference in patient characteristics amongst groups, including the proportion of intraoperative vasoactive drug use and adverse cardiovascular events during the follow-up period. Heart rate, mean blood pressure, central venous pressure, and cardiac output were not remarkably different between the two groups at any time point. Perioperative reperfusion could aggravate myocardial injury in SPKT. Dex may be considered a way to reduce myocardial injury caused by inflammatory action by decreasing the release of inflammatory factors. Trial Registration Number: Chinese Clinical Trial Registry ID: ChiCTR2200060084.

Differences in circulating cardiac troponin I and T in acute and chronic cardiac disease

Abstract Background Clinical practice and guidelines assume that cardiac troponin I (cTnI) and cTnT are interchangeable, reflecting identical pathophysiological processes. However, it is unknown if cTnI and cTnT really are equivalent measures in different pathophysiological settings. Purpose To highlight potential differences in the release of cTnI and cTnT. Methods Large pooled cohort analysis including extensively characterized individuals, stratified into three groups: no cardiac disease (normal aging), chronic cardiac disease, and acute cardiac disease. Circulating cTnI and cTnT concentrations were measured blinded to clinical data using high-sensitivity assays (hs-cTnI-Architect, hs-cTnT-Elecsys) and their ratio calculated. Findings were validated using a second hs-cTnI assay (hs-cTnI-Clarity). Results Among 8719 individuals, 29% female, 10% had no known cardiac disease, 71% chronic cardiac disease, and 20% acute cardiac disease. Baseline characteristics including renal function were comparable between individuals with chronic and acute cardiac disease. Normal aging (without cardiac disease) was associated with a disproportional increase in cTnT versus cTnI (low cTnI/cTnT ratio, median 0.50, IQR 0.38–0.68). Although older, patients with chronic cardiac disease had a slightly higher cTnI/cTnT ratio (median 0.53, IQR 0.37–0.79, p&amp;lt;0.05). In contrast, in patients with acute cardiac disease, cTnI concentrations were disproportionally elevated compared to cTnT concentrations, resulting in a cTnI/cTnT ratio of 1.96 (IQR 0.93–4.73, p&amp;lt;0.001). Internal validation using a second hs-cTnI assay confirmed these findings. Conclusion These findings suggest relevant differences in the release of cTnI and cTnT with a greater release of cTnT versus cTnI in normal aging and a disproportional increase in cTnI versus cTnT in acute cardiac disease. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Swiss National Science Foundation

Performance of high-sensitivity cardiac troponin T versus I for the early diagnosis of myocardial infarction

Abstract Background Clinical practice guidelines assume that both cardiac troponin (cTn) T and cTnI concentrations reflect identical pathophysiological processes and are equally effective in the detection of myocardial injury. However, there are differences between cTnT and cTnI that have been reported. Purpose The aim of this study was to directly compare the diagnostic performance of high-sensitivity cardiac troponin (hs-cTn) T versus hs-cTnI for the early diagnosis of acute myocardial infarction (MI). Methods In a prospective multicentre study, diagnostic and prognostic accuracies of hs-cTnT and I were analyzed in consecutive patients presenting to the emergency department with acute chest pain. The final diagnosis was adjudicated by two independent cardiologists using all information pertaining to the individual patient according to the fourth universal definition of MI. Adjudication of the final diagnoses was performed twice: once using serial measurements of hs-cTnT and once using hs-cTnI. Furthermore, the clinical performance of hs-cTnT/I when embedded in the European Society of Cardiology (ESC) 0/1h-algorithm was assessed. Results Among 5087 consecutive patients (median [Interquartile range, IQR] age 61 [49.0, 74.0] years, 33.2% female), 951 (18.7%) and 901 patients (17.7%) had an adjudicated final diagnosis of non-ST-segment elevation myocardial infarction (NSTEMI) when using serial measurements of hs-cTnT and hs-cTnI for adjudication, respectively. Diagnostic accuracy was very high for both hs-cTnT and hs-cTnI and comparable when using hs-cTnT for adjudication (hs-cTnT: area under the curve [AUC] 0.93 [95% CI 0.92–0.94] versus hs-cTnI AUC 0.93 [95% CI 0.92–0.94]; p=0.891). However, when using serial measurements of hs-cTnI for adjudication, diagnostic accuracy was significantly higher for hs-cTnI (AUC 0.93 [95% CI 0.92–0.94] versus AUC 0.94 [95% CI 0.94–0.95], p&amp;lt;0.001; Figure 1). This was confirmed in subgroup analyses including early presenter (≤3h), patients with renal failure, known coronary artery disease and elderly (≥70 years). However, both assays performed excellent with very high safety for rule-out and high accuracy for rule-in MI when embedded in the ESC 0/1h-algorithm. Prognostic accuracies for 730-day all-cause mortality and cardiovascular death were significantly higher for hs-cTnT compared to hs-cTnI (Figure 2). Conclusions While there seem to be differences between hs-cTnT and hs-cTnI in their diagnostic and prognostic performance, clinical relevance needs to be further evaluated since both assays performed excellent when embedded in their respective early triage algorithms. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Swiss National Foundation, Swiss Heart Foundation

Effects of Dexmedetomidine Pretreatment, Posttreatment, and Whole-Course Pumping on Myocardial Damage during Cardiac Valve Replacement.

To compare the effects of dexmedetomidine (DEX) pretreatment, posttreatment, and whole-course pumping on myocardial protection during cardiac valve replacement.One hundred and twenty patients undergoing cardiac valve replacement were randomly divided into the follow groups: DEX pretreatment (D1 group), DEX posttreatment (D2 group), DEX whole-course pumping (D3 group), and Control (C group). The concentrations of cardiac troponin I (cTnI), malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), rate of spontaneous heart rebound after aortic opening, time to heart rebound, incidence of arrhythmia, and use of sufentanil and vasoactive drugs were recorded.Compared with group C, the concentrations of cTnI, MDA, and TNF-α in the D1, D2, and D3 groups were lower, especially in the latter. The time to heart rebound was prolonged in all three groups (P < 0.05). The rate of automatic rebound was increased (P < 0.05) while the incidence of arrhythmia was decreased (P < 0.05) in all groups compared with group C. Group D3 had the highest rate of automatic rebound and the lowest incidence of arrhythmia. Compared with groups C and D2, the use of sufentanil and dopamine was lower in groups D1 and D3 (P < 0.05), especially in the latter.During cardiac valve replacement, DEX pretreatment, posttreatment, and whole-course pumping could have myocardial protective effects. The latter showed better effects.

Cardiac troponin I in healthy Norwegian Forest Cat, Birman and domestic shorthair cats, and in cats with hypertrophic cardiomyopathy.

ObjectivesThe aims of this study were to assess the potential associations between the serum cardiac troponin I (cTnI) concentration in healthy cats and feline characteristics, systolic blood pressure, heart rate (HR), echocardiographic measurements and storage time; and to compare cTnI concentrations in healthy cats with concentrations in cats with hypertrophic cardiomyopathy (HCM), with or without left atrial enlargement (LAE) and in cats with HCM, to assess potential associations between cTnI concentration and echocardiographic variables.MethodsCardiac TnI was analysed using an Abbott ARCHITECT ci16200 analyser in serum from prospectively included healthy Norwegian Forest Cat (NF; n = 33), Birman (n = 33) and domestic shorthair (DSH; n = 30) cats, and from 39 cats with HCM, with or without LAE.ResultsIn healthy cats, higher cTnI concentrations were found in Birman cats than in NF cats (P = 0.014) and in neutered male cats than in intact females (P = 0.032). Cardiac TnI was positively associated with HR (P <0.0001). In cats with HCM, cTnI concentration was positively associated with left ventricular wall thickness and with left atrial-to-aortic root ratio (all P ⩽0.010). Cats with HCM had higher cTnI concentrations than healthy cats, and cTnI concentrations were higher in cats with HCM and LAE than in those with HCM without LAE (all P = 0.0003).Conclusions and relevanceBreed and sex may affect serum cTnI concentrations in healthy cats. The cTnI concentration increased with increasing severity of HCM.

Porous graphitic carbon nitrides integrated biosensor for sensitive detection of cardiac troponin I

Early diagnosis of cardiovascular diseases (CVDs) has the potential to save millions of lives each year. Sensitive quantitative measurement of blood cardiac troponin I (cTnI) is required for early diagnosis of CVDs. Porous graphitic carbon nitride (PCN) nanomaterials integrated biosensor that detects picogram/mL concentrations of cTnI is reported. PCN is an updated version of graphitic carbon nitride (GCN) with improved porosity and electronic structure. A rapid two-step chemical method was described to synthesize PCN and gold nanoparticles functionalized PCN (PCN-AuNPs). The modification of the electrode surface with PCN materials had a significant impact on the electrochemically active surface area (EASA), interfacial electron transport, aptamer immobilization, and biosensing performance. The use of PCN nanomaterial in cTnI aptasensing resulted in a 3.2-fold increase in signal amplification. PCN-AuNPs found practically applicable in human blood serum (cTnI-spiked). Furthermore, a low-cost and user-friendly sensing platform has been demonstrated by integrating a PCN-AuNPs aptasensor, a custom-made miniaturized potentiostat, and a smartphone, which provided rapid, sensitive point-of-care (PoC) analysis of cTnI. Highly sensitive detection limit (0.01 pg/mL), rapid analysis time (2 min), and small sample volume (20 μL) are the other advantages of this nano-biosensor.

Role of Keap1-Nrf2/ARE signal transduction pathway in protection of dexmedetomidine preconditioning against myocardial ischemia/reperfusion injury.

Objective: To explore the role and mechanism of the Kelch sample related protein-1-nuclear factor erythroid-2 related factor 2/antioxidant response element (Keap1-Nrf2/ARE) signaling pathway in protection of dexmedetomidine (DEX) preconditioning against myocardial ischemia/reperfusion injury (MIRI). Methods: A total of 70 male SD rats were randomly divided into seven equal groups (n=10): blank control (S group), ischemia/reperfusion injury (C group), DEX preconditioning (DEX group), tertiary butylhydroquinone (tBHQ) control (tBHQ group), combined tBHQ and DEX preconditioning (tBHQ+DEX group), all-trans retinoic acid (ATRA) control (ATRA group), and combined ATRA and DEX preconditioning (ATRA+DEX group). Serum creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI) concentrations were measured by ELISA kits, and the infarct size (IS) was assessed by Evan’s blue and 2,3,5-triphenyltetrazolium chloride (TTC) staining. Oxidative stress was assessed through Western blotting for expression of Keap1-Nrf2/ARE pathway members and oxidative stress markers. Results: Cardioprotection of DEX, tBHQ, and tBHQ+DEX preconditioning treatments were shown as lower concentrations of serum CK-MB and cTnI and a smaller IS following MIRI in rats compared with those of MIRI rats without pre-treatment. In addition, tBHQ+DEX preconditioning exhibited stronger myocardial protection compared with DEX preconditioning. Mechanistically, the cardioprotection offered by DEX, tBHQ, and tBHQ+DEX preconditioning treatments was mediated via exerting antioxidant stress through activation of the Keap1-Nrf2/ARE signal transduction pathway. Conversely, the protective effects of DEX were diminished by blocking the Keap1-Nrf2/ARE pathway with inhibitor ATRA. Conclusion: DEX preconditioning protects against MIRI by exerting antioxidant stress through activation of the Keap1-Nrf2/ARE signal transduction pathway, while inhibition of the Keap1-Nrf2/ARE signal transduction pathway reverses the protective effect of DEX preconditioning on MIRI.

Danshensu exerts cardioprotective effects in rats with acute myocardial infarction via reduction of infiltration of inflammatory cells and mitigation of myocardial fibrosis

Purpose: To investigate the mitigative impact of danshensu on heart tissues in acute myocardial infarction (AMI) rats, and the mechanism of action involved.&#x0D; Methods: Seventy-five male Sprague-Dawley (SD) rats were used in this study. After successful induction of myocardial infarction, the rats were divided into model group (MG), low-dose danshensu group (LDG; 15 mg/kg), middle-dose danshensu group (MDG; 30 mg/kg), and high-dose danshensu group (HDG; 60 mg/kg), with 15 rats per group. Rats in sham group (SG; n = 15) served as control. Serum levels of biochemical indicators and expressions of various proteins in myocardial tissue were determined using Western blotting, and compared amongst the rat groups.&#x0D; Results: Serum cTnI concentrations in MDG and HDG were significantly decreased, relative to the corresponding concentrations in MDG. There were significantly lower serum concentrations of IL-1 in MDG and HDG than in model rats. Rats in HDG had lower serum IL-6 concentration than MG rats, while TNF-α levels were down-regulated in MDG and HDG, relative to MG (p &lt; 0.05).&#x0D; Conclusion: Danshensu protects the heart function of rats with AMI by decreasing inflammationderived cells and mitigating myocardial fibrosis. Thus, it may be useful in the management of AMI in humans but clinical trials are necessary to ascertain this.&#x0D; Keywords: Danshens; Acute myocardial infarction; Myocardial ischemia-reperfusion; Myocardial fibrosis

Serum cardiac troponin I concentration increases in sheep with uterine torsion

It is currently unclear whether myocardial damage occurs in sheep suffering from uterine torsion. Increased serum cardiac troponin I (cTnI) concentration is considered as the gold standard indicator of myocardial damage. The purpose of this study was to investigate the serum cTnI concentrations in sheep with uterine torsion and the relationship of serum cTnI concentrations in cases of uterine torsion to hematological and biochemical variables, the degree of uterine torsion and the estimated duration of labor. A total of 32 sheep were included in the study and were assigned to uterine torsion (UT, n = 14), other types of dystocia requiring cesarean section or manual assistance (OTD, n = 11), and unassisted vaginal delivery (UVD, n = 7) groups based on inclusion criteria. Advia Centaur TnI-Ultra, a human-specific immunoassay, was used to measure serum cTnI concentrations. The median serum cTnI concentration was significantly higher in the UT group than in the OTD and UVD groups (UT: 0.507 ng/mL (0.040–18.521); OTD: 0.044 ng/mL (0.016–0.135); UVD: 0.036 ng/mL (0.023–0.059); p < 0.001). In uterine torsion cases, serum cTnI concentrations correlated positively with serum CK (r = 0.556, p = 0.042), AST (r = 0.613, p = 0.022) and LDH activities (r = 0.609, p = 0.024), and degree of uterine torsion (r = 0.563, p = 0.036). The results indicated that uterine torsion leads to an increase in serum cTnI concentration. Further investigations can be undertaken to explore possible factors contributing to the release of cTnI from the myocardium into the circulation and whether the myocardial damage in uterine torsion is reversible or irreversible.

Comparison of ADVIA Centaur ultra-sensitive and high-sensitive assays for troponin I in serum

Cardiac troponin I (cTnI) is a standard biomarker for the diagnosis of acute myocardial infarction (AMI). While older, ultra-sensitive cTnI (us-cTnI) assays use the 99th percentile as the reference threshold, newer high-sensitive cTnI (hs-cTnI) assays use the limit of detection or functional sensitivity instead. However, little has been done to systematically compare these two methods. The present study also served as a validation of hs-cTnI in our laboratory. Here, we compared the results obtained from the blood serum obtained from 8810 patients using the us-cTnI and the hs-cTnI assays run in tandem on the ADVIA Centaur XP analyser. We found that in 2279 samples the concentration of cTnI measured with the ultra-sensitive method was below the detection limit, while with the high-sensitive method, only 540 were below the detection limit. We also compared results from these assays with the ultimate diagnosis of a subset of individuals. The analysis of the results below cut-off with the ultra-sensitive method showed that this method would not detect 96 cases related to heart disorder. Overall, the main finding of our research is that hs-cTnI is the preferable option and is able to be deployed effectively in the laboratory setting.

Evaluation of new and old biomarkers in dogs with degenerative mitral valve disease

BackgroundDogs with degenerative mitral valve disease are commonly presented to small animal clinicians. Diagnosis, clinical staging, and therapeutic design are based on a combination of clinical examination, radiography, and echocardiography. To support diagnosis and clinical monitoring, a multi-marker-based approach would be conceivable. The aim of this study was to investigate the suitability of Galectin-3 and interleukin-1 receptor-like 1 protein (ST2) in dogs with degenerative mitral valve disease in accordance with N-terminal-prohormone-B-type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI). For this purpose, serum concentrations of Galectin-3 and ST2 of 64 dogs with different stages of mitral valve disease and 21 dogs without cardiac disease were analyzed at the first examination and six months later. Echocardiography, blood cell count and clinical chemistry were performed and established biomarkers NT-proBNP and cTnI were measured additionally. Differences in the biomarker concentrations between all groups at both timepoints and the change in biomarker concentrations from first to second evaluation was investigated. Furthermore, correlations of each biomarker, between biomarkers and echocardiographic measurements, were calculated. Finally, the receiver-operating characteristic curve and the area under the curve analysis were performed to differentiate between disease stages and controls.ResultsSerum concentrations of Galectin-3 and ST2 were not statistically different between canine patients in the respective stages of mitral valve disease or in comparison to dogs in the control group at any timepoint. A significant increase in ST2 concentrations from the baseline to the follow-up examination was observed in dogs classified as stage B1 and the control group. The concentrations of NT-proBNP and cTnI in stage C dogs were significantly increased in comparison to the other groups.ConclusionsIn this study, no relation between Galectin-3 and ST2 levels to the presence or stage of mitral valve disease could be detected. Nevertheless, considering the increase in ST2 concentrations from the first to second measurement, its value on monitoring disease progress could be feasible. In agreement with previous studies, NT-proBNP and cTnI have once more proven their utility in assessing disease severity. The approach of examining new cardiac biomarkers in dogs is still worth pursuing.

Rationale and Design of the Cardiac CARE Trial: A Randomized Trial of Troponin-Guided Neurohormonal Blockade for the Prevention of Anthracycline Cardiotoxicity.

Anthracyclines are effective cytotoxic drugs used in the treatment of breast cancer and lymphoma but are associated with myocardial injury, left ventricular dysfunction, and heart failure. Anthracycline-induced cardiotoxicity is highly variable in severity and without a proven therapeutic intervention. β-Adrenergic receptor blockers and renin-angiotensin-system inhibitor therapies have been associated with modest cardioprotective effects in unselected patients. The Cardiac CARE trial is a multicentre prospective randomized open-label blinded end point trial of combination β-adrenergic receptor blocker and renin-angiotensin-system inhibitor therapy in patients with breast cancer and non-Hodgkin lymphoma receiving anthracycline chemotherapy that is associated with myocardial injury. Patients at higher risk of cardiotoxicity with plasma high-sensitivity cTnI (cardiac troponin I) concentrations in the upper tertile at the end of chemotherapy are randomized to standard of care plus combination candesartan and carvedilol therapy or standard of care alone. All patients undergo cardiac magnetic resonance imaging before and 6 months after anthracycline treatment. The primary end point is the change in left ventricular ejection fraction at 6 months after chemotherapy. In low-risk nonrandomized patients, left ventricular ejection fraction before and 6 months after anthracycline will be compared with define the specificity of the high-sensitivity cTnI assay for identifying low-risk participants who do not develop left ventricular systolic dysfunction. Cardiac CARE will examine whether cardiac biomarker monitoring identifies patients at risk of left ventricular dysfunction following anthracycline chemotherapy and whether troponin-guided treatment with combination candesartan and carvedilol therapy prevents the development of left ventricular dysfunction in these high-risk patients.

A long duration race induces a decrease of left ventricular strains, twisting mechanics and myocardial work in trained adolescents

Background: We investigated the acute cardiac consequences of a long-duration (>5 h) adventure race in adolescent athletes from evaluations of left ventricular (LV) strains and myocardial work. Methods: Twenty trained male adolescents (i.e. 8 ± 4 hours/week of endurance sports) aged 14 to 17 years participated in a competitive long-duration adventure race. Blood samples were collected before, immediately and 24 h after the race to determine the time course of troponin I (cTnI) considered as a myocardial damage biomarker. Resting echocardiography were conducted before and after the race to assess myocardial regional strains, LV twisting mechanics and myocardial work using speckle tracking echocardiography. Results: The mean completion time of the race was 05:38 ± 00:20 h, with a mean heart rate (HR) of 83 ± 5% of maximal HR. cTnI concentration significantly increased in 16/20 participants after the race (pre: 0.001 ± 0.002 vs. post: 0.244 ± 0.203 ng·dL-1, p < 0.001) and returned to baseline within 24 h. Stroke volume, ejection fraction and global longitudinal strains remained unchanged after the race while LV twist and global myocardial work significantly decreased (8.6 ± 3.3 vs. 6.3 ± 3.3 deg and 2080 ± 250 vs. 1781 ± 334 mmHg%, p < 0.05). Diastolic function, indexes of myocardial relaxation and LV untwisting rate (-91.0 ± 19.0 vs. -56.4 ± 29.1 deg·s-1, p < 0.001) were affected after the race. Conclusion: We demonstrated for the first time that, in trained adolescents, a high-intensity endurance exercise of several hours induced an increase of the cTnI concentration associated with an alteration of myocardial function.