The aim of our study was to compare the diagnostic performance of cardiac troponin T (cTnT) and cardiac troponin I (cTnI) in three groups of rabbits: 1) control (saline 1 ml/kg i.v.); 2) daunorubicin (3 mg/kg i.v.); 3) daunorubicin (3 mg/kg i.v.) + dexrazoxane (60 mg/kg i.p.). The drugs were given once a week, 10 administrations. The concentration of cTnT was measured using Elecsys Troponin T STAT Immunoassay (Roche). The concentration of cTnI was measured using AxSYM Troponin I (Abbott). The linear regression model was applied to see if there is a dependence between cTnT and cTnI. The coefficient of determination (R2 = 0.79) was acceptable only in the control group. In the remaining cases (i.e. in the daunorubicin group and in the daunorubicin + dexrazoxane treated group) R2 was too small (0.53, and 0.06). We may conclude that in rabbits after repeated administration of cardiotoxic or cardioprotective drugs meaningful dependence between cTnT and cTnI was not found. The choice of the most suitable cardiomarker in laboratory animals deserves further studies.

• MeSH
• biologické markery krev   MeSH
• daunomycin toxicita   MeSH
• kardiomyopatie chemicky indukované   diagnóza   MeSH
• králíci MeSH
• ochranné látky aplikace a dávkování   MeSH
• protinádorová antibiotika toxicita   MeSH
• razoxan aplikace a dávkování   MeSH
• srdce účinky léků   MeSH
• troponin T krev   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• daunomycin MeSH
• ochranné látky MeSH
• protinádorová antibiotika MeSH
• razoxan MeSH
• troponin T MeSH

Tn is a unique translational biomarker in cardiology whose potential has not been diminished in the new era of high sensitive assays. cTns can be valuable markers in cardiac diseases as well as in infectious diseases and respiratory diseases. Furthermore, the role of cTns is growing in the routine evaluation of cardioxicity and in determining the efficacy/safety ratio of novel cardioprotective strategies in clinical settings. cTns can detect myocardial injury not only in a wide spectrum of laboratory animals in experimental studies in vivo, but also in isolated heart models or cardiomyocytes in vitro. The crucial issue regarding the cross-species usage of cardiac troponin investigation remains the choice of cardiac troponin testing. This review summarizes the recent proteomic data on aminoacid sequences of cTnT and cTnI in various species, as well as selected analytical characteristics of human cardiac troponin high-sensitivity assays. Due to the highly phylogenetically conserved structure of troponins, the same bioindicator can be investigated using the same method in both clinical and experimental cardiology, thus contributing to a better understanding of the pathogenesis of cardiac diseases as well as to increased effectiveness of troponin use in clinical practice. Measuring cardiac troponins using commercially available human high-sensitivity cardiac troponin tests with convenient antibodies selected on the basis of adequate proteomic knowledge can solve many issues which would otherwise be difficult to address in clinical settings for various ethical and practical reasons. Our survey could help elaborate the practical guidelines for optimizing the choice of cTns assay in cardiology.

• Klíčová slova
• cardiac biomarkers, cardiac troponin, cross-species use of cardiac troponins, high-sensitivity assay, proteomics of troponins, toxicology studies,
• MeSH
• biologické markery metabolismus   MeSH
• biotest metody   MeSH
• lidé MeSH
• myokard metabolismus   patologie   MeSH
• nemoci srdce diagnóza   metabolismus   patologie   MeSH
• proteomika MeSH
• troponin I izolace a purifikace   metabolismus   MeSH
• troponin T izolace a purifikace   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• biologické markery MeSH
• troponin I MeSH
• troponin T MeSH

BACKGROUND: Cardiac troponins (cTns) seem to be more sensitive for the detection of anthracycline cardiotoxicity than the currently recommended method of monitoring LV systolic function. However, the optimal timing of blood sampling remains unknown. Hence, the aims of the present study were to determine the precise diagnostic window for cTns during the development of chronic anthracycline cardiotoxicity and to evaluate their predictive value. METHODS: Cardiotoxicity was induced in rabbits with daunorubicin (3mg/kg, weekly, for 8 weeks). Blood samples were collected 2-168 h after the 1st, 5th and 8th drug administrations, and concentrations of cTns were determined using highly sensitive assays: hs cTnT (Roche) and hs cTnI (Abbott). RESULTS: The plasma levels of cTns progressively increased with the rising number of chemotherapy cycles. While only a mild non-significant increase in both cTn levels occurred after the first daunorubicin dose, a significant rise was observed after the 5th and 8th administrations. Two hours after these administrations, a significant increase occurred with a peak between 4-6h and a decline until 24h. Discrete cTn release continued even after cessation of the therapy. While greater variability of cTn levels was observed around the peak concentrations, the values did not correspond well with the severity of LV systolic dysfunction. Unlike AMI in cardiotoxicity, cTn elevations may be better associated with cumulative dose and concentrations at steady state than cmax. CONCLUSIONS: To the best of our knowledge, this is the first study to precisely describe the diagnostic window and predictive value of cTns in anthracycline cardiotoxicity.

• Klíčová slova
• Anthracyclines, Cardiomyopathy, Cardiotoxicity, Chemotherapy, Heart failure, High sensitive troponin assay,
• MeSH
• antracykliny toxicita   MeSH
• biologické markery krev   metabolismus   MeSH
• daunomycin toxicita   MeSH
• echokardiografie MeSH
• kardiomyopatie krev   chemicky indukované   MeSH
• kardiotoxicita krev   diagnostické zobrazování   MeSH
• králíci MeSH
• modely nemocí na zvířatech MeSH
• prediktivní hodnota testů MeSH
• protinádorová antibiotika toxicita   MeSH
• regresní analýza MeSH
• srdce účinky léků   fyziologie   MeSH
• systola účinky léků   fyziologie   MeSH
• troponin I krev   MeSH
• troponin T krev   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antracykliny MeSH
• biologické markery MeSH
• daunomycin MeSH
• protinádorová antibiotika MeSH
• troponin I MeSH
• troponin T MeSH

Cardiac troponin T (cTnT) and troponin I (cTnI) are becoming acknowledged as useful biochemical markers of drug-induced cardiotoxicity. In this study we examined the release kinetics of cTnT and cTnI using an in vitro model of isolated rat neonatal ventricular cardiomyocytes (NVCM, 72h treatment with 0.1-3microM of daunorubicin) and compared it with data from a rabbit model of chronic anthracycline-induced cardiomyopathy in vivo (3mg/kg of daunorubicin weekly, 10 weeks). In cell-culture media, the cTnI and cTnT concentrations were concentration- and time-dependently increasing in response to daunorubicin exposure and were negatively exponentially related to cardiomyocyte viability. With 3microM daunorubicin, the relative increase of AUC of cTnT and cTnI was 2.4- and 5.3-fold higher than the increase of LDH activity, respectively. In rabbits, the daunorubicin-induced cardiomyopathy was associated with progressive increase of both cTnT and cTnI. Although the correlation between cTnT and cTnI cumulative release (AUCs) was found (R=0.81; P<0.01) and both cardiac troponins corresponded well with the echocardiographically-assessed systolic dysfunction (R=0.83 and 0.81 for cTnT and cTnI, respectively; P<0.001), the first significant increase in cTnI levels was observed earlier (at a cumulative daunorubicin dose of 200mg/m(2)) than with cTnT (350mg/m(2)). In conclusion, our study has confirmed cTnT and cTnI as very sensitive and specific markers of anthracycline-induced cardiotoxicity. The troponins can become not only the bridge between the clinical and experimental studies of drug-induced cardiotoxicity but also the linkage between the preclinical experiments in vitro and in vivo.

• MeSH
• biologické markery krev   MeSH
• daunomycin škodlivé účinky   MeSH
• kardiomyocyty * účinky léků   metabolismus   patologie   MeSH
• kardiomyopatie krev   chemicky indukované   metabolismus   MeSH
• králíci MeSH
• krysa rodu Rattus MeSH
• kultivované buňky MeSH
• novorozená zvířata MeSH
• protinádorová antibiotika škodlivé účinky   MeSH
• troponin I krev   MeSH
• troponin T krev   MeSH
• viabilita buněk účinky léků   MeSH
• western blotting MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• daunomycin MeSH
• protinádorová antibiotika MeSH
• troponin I MeSH
• troponin T MeSH

PURPOSE: Cardiac troponin T (cTnT) plasma concentration is considered a useful marker of anthracycline-induced cardiomyopathy. In this study we used daunorubicin-treated Chinchilla rabbits as a model to investigate the relationship between left ventricular contractility and cTnT plasma concentrations. METHODS: Two groups of animals were used: a control group (n=8) received i.v. saline, and an experimental group (n=11) received daunorubicin (3 mg/kg, i.v.). The substances were administered once weekly for 10 weeks, and 5-7 days after the last administration, left ventricular cardiac contractility (dP/dtmax) was invasively measured as a contractility index and blood was sampled for cTnT concentration determination (Elecsys Troponin T STAT immunoassay). RESULTS: Cardiac contractility was significantly lower in seven surviving daunorubicin-treated animals than in control animals (745.7+/-69.3 vs 1393.4+/-25.5 kPa/s; P<0.001), while cTnT plasma concentrations were significantly increased (medians 0.278 vs 0.000 ng/ml; P<0.001). When the dP/dtmax values of individual daunorubicin-treated animals were plotted against the corresponding cTnT plasma concentrations, a close negative linear correlation was found (R=-0.910; P<0.005; regression equation: dP/dtmax=-1861*cTnT+1234). CONCLUSIONS: This study suggests that determination of cTnT plasma levels, which is simple and inexpensive, could be used in anthracycline-treated patients for left ventricular systolic function assessment and contractility estimation.

• MeSH
• biologické markery MeSH
• činčila MeSH
• daunomycin toxicita   MeSH
• dysfunkce levé srdeční komory chemicky indukované   metabolismus   MeSH
• funkce levé komory srdeční účinky léků   MeSH
• kardiomyopatie chemicky indukované   metabolismus   MeSH
• kontrakce myokardu účinky léků   MeSH
• králíci MeSH
• myokard metabolismus   MeSH
• protinádorová antibiotika toxicita   MeSH
• troponin T metabolismus   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• daunomycin MeSH
• protinádorová antibiotika MeSH
• troponin T MeSH

BACKGROUND: High-sensitivity cardiac troponin T (hs-cTnT) blood concentrations were shown to exhibit a diurnal rhythm, characterized by gradually decreasing concentrations throughout daytime, rising concentrations during nighttime and peak concentrations in the morning. We aimed to investigate whether this also applies to (h)s-cTnI assays and whether it would affect diagnostic accuracy for acute myocardial infarction (AMI). METHODS: Blood concentrations of cTnI were measured at presentation and after 1 h using four different cTnI assays: three commonly used sensitive (s-cTnI Architect, Ultra and Accu) and one experimental high-sensitivity assay (hs-cTnI Accu) in a prospective multicenter diagnostic study of patients presenting to the emergency department with suspected AMI. These concentrations and their diagnostic accuracy for AMI (quantified by the area under the curve (AUC)) were compared between morning (11 p.m. to 2 p.m.) and evening (2 p.m. to 11 p.m.) presenters. RESULTS: Among 2601 patients, AMI was the final diagnosis in 17.6% of patients. Concentrations of (h)s-cTnI as measured using all four assays were comparable in patients presenting in the morning versus patients presenting in the evening. Diagnostic accuracy for AMI of all four (h)s-cTnI assays were high and comparable between patients presenting in the morning versus presenting in the evening (AUC at presentation: 0.90 vs 0.93 for s-cTnI Architect; 0.91 vs 0.94 for s-cTnI Ultra; 0.89 vs 0.94 for s-cTnI Accu; 0.91 vs 0.94 for hs-cTnI Accu). CONCLUSIONS: Cardiac TnI does not seem to express a diurnal rhythm. Diagnostic accuracy for AMI is very high and does not differ with time of presentation. CLINICAL TRIAL REGISTRATION: NCT00470587, http://clinicaltrials.gov/show/NCT00470587.

• Klíčová slova
• Acute myocardial infarction, Circadian rhythm, Diagnosis, High-sensitivity cardiac troponin I,
• MeSH
• biologické markery krev   MeSH
• cirkadiánní rytmus fyziologie   MeSH
• infarkt myokardu krev   diagnostické zobrazování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• prospektivní studie MeSH
• senioři MeSH
• troponin I krev   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH
• Názvy látek
• biologické markery MeSH
• troponin I MeSH

Matrix metalloproteinases (MMPs), activated by oxidative stress, play a key role during cardiac remodeling. In the present study we aimed to assess the role of MMPs in experimental cardiomyopathy induced by repeated 10-week administration of daunorubicin (3 mg/kg i.v.) to rabbits. In the daunorubicin group, the plasma cardiac troponin T levels (cTnT - a marker of myocardial necrosis) were significantly increased (p<0.05), commencing with the 8th administration compared with the controls. The amount of collagen (an estimate of fibrosis) was also significantly higher in the daunorubicin group (13.39 +/- 0.97 mg/g wet weight) compared to the control group (10.03 +/- 0.65 mg/g wet weight). In both groups, the LV MMP-activity was observed only in the gelatine substrate in the 70 kDa region (MMP-2), while no MMPs activities were detectable either in the casein or collagen containing zymograms. At the end of the experiment, the MMP-2 activity was slightly up-regulated (by 16 %) compared with the controls.

• MeSH
• daunomycin toxicita   MeSH
• kardiomyopatie chemicky indukované   enzymologie   metabolismus   patofyziologie   MeSH
• kolagen metabolismus   MeSH
• králíci MeSH
• matrixové metaloproteinasy metabolismus   MeSH
• remodelace komor MeSH
• troponin T metabolismus   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• daunomycin MeSH
• kolagen MeSH
• matrixové metaloproteinasy MeSH
• troponin T MeSH

Recently, cardiac troponin T (cTnT) has been shown to be a sensitive marker of anthracycline-induced cardiomyopathy. In our study, the cardiotoxicity of repeated i.v. administration (once a week, 10 administrations) of daunorubicin combined with new antineoplastic drugs (with mild side-effects) were followed in two groups of rabbits: 1) Dimefluron (3,9-dimethoxybenfluron hydrochloride-12 mg/kg) + daunorubicin (3 mg/kg), 2) Oracin (6-[2-(2-hydroxyethyl)aminoethyl]-5,11-dioxo-5,6-dihydro-11H- indeno[1,2c]isoquinoline hydrochloride--10 mg/kg) + daunorubicin (3 mg/kg) and compared with the control group (saline--1 ml/kg) and the group with experimentally induced cardiomyopathy (daunorubicin--3 mg/kg). The concentration of cTnT in heparinized plasma samples was measured using commercial kit (Roche). In the control group, plasma levels of cTnT were always within the physiological range (i.e. lower than 0.1 microgram/l) during the experiment. During the development of daunorubicin-induced cardiomyopathy, after the eighth administration of drug, cTnT was significantly higher (0.31 +/- 0.11 microgram/l) in animals with premature deaths compared with the rest of the group (0.04 +/- 0.03 microgram/l). The animals with pathological values of cTnT were at higher risk of premature deaths (P = 0.0006). The combination of daunorubicin either with Oracin or with Dimefluron caused neither significant changes of cTnT levels nor significant deterioration of other followed-up parameters (especially, functional and toxicological parameters). Similarly to the daunorubicin group, the animals with pathological levels of cTnT after the eighth administration of antineoplastic drugs were at higher risk of premature death (P = 0.025). Our results show that the plasma concentration of cardiac troponin T could be a suitable predictive marker of cardiotoxicity of antineoplastic drugs.

• MeSH
• biologické markery krev   MeSH
• daunomycin aplikace a dávkování   toxicita   MeSH
• ethanolaminy aplikace a dávkování   toxicita   MeSH
• fluoreny aplikace a dávkování   toxicita   MeSH
• isochinoliny aplikace a dávkování   toxicita   MeSH
• kardiomyopatie chemicky indukované   diagnóza   MeSH
• králíci MeSH
• protinádorová antibiotika aplikace a dávkování   toxicita   MeSH
• protokoly protinádorové kombinované chemoterapie toxicita   MeSH
• troponin T krev   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• zvířata MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 3,9-dimethoxybenfluron MeSH Prohlížeč
• biologické markery MeSH
• daunomycin MeSH
• ethanolaminy MeSH
• fluoreny MeSH
• isochinoliny MeSH
• oracine MeSH Prohlížeč
• protinádorová antibiotika MeSH
• troponin T MeSH

Acute respiratory distress syndrome (ARDS) is characterized by diffuse lung damage, inflammation, oedema formation, and surfactant dysfunction leading to hypoxemia. Severe ARDS can accelerate the injury of other organs, worsening the patient´s status. There is an evidence that the lung tissue injury affects the right heart function causing cor pulmonale. However, heart tissue changes associated with ARDS are still poorly known. Therefore, this study evaluated oxidative and inflammatory modifications of the heart tissue in two experimental models of ARDS induced in New Zealand rabbits by intratracheal instillation of neonatal meconium (100 mg/kg) or by repetitive lung lavages with saline (30 ml/kg). Since induction of the respiratory insufficiency, all animals were oxygen-ventilated for next 5 h. Total and differential counts of leukocytes were measured in the arterial blood, markers of myocardial injury [(troponin, creatine kinase - myocardial band (CK-MB), lactate dehydrogenase (LD)] in the plasma, and markers of inflammation [tumour necrosis factor (TNF)alpha, interleukin (IL)-6], cardiovascular risk [galectin-3 (Gal-3)], oxidative changes [thiobarbituric acid reactive substances (TBARS), 3-nitrotyrosine (3NT)], and vascular damage [receptor for advanced glycation end products (RAGE)] in the heart tissue. Apoptosis of heart cells was investigated immunohistochemically. In both ARDS models, counts of total leukocytes and neutrophils in the blood, markers of myocardial injury, inflammation, oxidative and vascular damage in the plasma and heart tissue, and heart cell apoptosis increased compared to controls. This study indicates that changes associated with ARDS may contribute to early heart damage what can potentially deteriorate the cardiac function and contribute to its failure.

• MeSH
• apoptóza fyziologie   MeSH
• biologické markery metabolismus   MeSH
• králíci MeSH
• modely nemocí na zvířatech MeSH
• oxidační stres fyziologie   MeSH
• poranění srdce metabolismus   patologie   MeSH
• poškození plic metabolismus   patologie   MeSH
• syndrom aspirace mekonia metabolismus   patologie   MeSH
• syndrom dechové tísně metabolismus   patologie   MeSH
• zánět metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH

AIM: Monitoring of cardiotoxicity of conventional and high-dose chemotherapy (HD-CT) with multiple biomarkers of cardiac injury - glycogen phosphorylase BB (GPBB), heart-type fatty acid binding protein (H-FABP), cardiac troponins (cTnT, cTnI), creatine kinase MB (CK-MB mass), myoglobin. METHODS: A total of 47 adult acute leukemia patients were studied - 24 patients treated with conventional CT containing anthracyclines (ANT) and 23 patients treated with HD-CT (myeloablative preparative regimen) followed by hematopoietic cell transplantation (HCT). Cardiac biomarkers were assessed prior to treatment (before CT/HD-CT), after first CT with ANT, after last CT with ANT in the first group, after HD-CT and after HCT in the second group. Values above the reference range were considered elevated. RESULTS: Before CT/HD-CT, all biomarkers of cardiac injury were below the cut-offs in all patients. GPBB increased above the cut-off (7.30 microg/L) in 4 (16.7%) patients after first CT and in 5 (20.8%) patients after last CT with ANT. GPBB increased above the cut-off in 5 (21.7%) patients after HD-CT and remained elevated in 5 (21.7%) patients after HCT. CTnI became elevated (above 0.40 microg/L) in 2 (8.3%) patients after first and last CT with ANT. Both patients with cTnI positivity had elevated GPBB. Other tested biomarkers remained below the cut-offs during the study. CONCLUSION: Our results suggest that GPBB could become a sensitive biomarker for detection of acute cardiotoxicity associated with conventional CT containing ANT and HD-CT followed by HCT. The predictive value for development of cardiomyopathy in the future is not known and should be evaluated during a prospective follow-up. Based on our data, a larger prospective and multicenter study would be most desirable to define the potential role of new circulating biomarkers in the assessment of cardiotoxicity in oncology.

• MeSH
• akutní myeloidní leukemie krev   farmakoterapie   chirurgie   MeSH
• dospělí MeSH
• FABP3 MeSH
• glykogenfosforylasa krev   MeSH
• kreatinkinasa, forma MB krev   MeSH
• lidé MeSH
• myoglobin krev   MeSH
• nádorové biomarkery krev   MeSH
• proteiny vázající mastné kyseliny krev   MeSH
• protinádorové látky aplikace a dávkování   škodlivé účinky   MeSH
• srdce účinky léků   MeSH
• transplantace hematopoetických kmenových buněk MeSH
• troponin I krev   MeSH
• troponin T krev   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• FABP3 protein, human MeSH Prohlížeč
• FABP3 MeSH
• glycogen phosphorylase BB, human MeSH Prohlížeč
• glykogenfosforylasa MeSH
• kreatinkinasa, forma MB MeSH
• myoglobin MeSH
• nádorové biomarkery MeSH
• proteiny vázající mastné kyseliny MeSH
• protinádorové látky MeSH
• troponin I MeSH
• troponin T MeSH