In this study, we investigated the mechanism underlying electrocardiogram (ECG) alterations in a rabbit model of acute pulmonary thromboembolism (PTE). Twelve healthy adult New Zealand white rabbits were used, with eight in the experimental group (PTE group) and four in the control group. After developing the rabbit model of acute PTE, ECG and coronary angiography were performed. HE staining was conducted on the right and left ventricular tissues, and polymerase chain reaction (PCR) was used to determine brain natriuretic peptide (BNP), tumor necrosis factor-alpha (TNF-?), and Troponin I (TNI) mRNA expression in the myocardium. There were considerable changes in the ST segment of the ECG in the PTE group. Coronary angiography revealed the absence of spasm, stenosis, and occlusion. In the plasma of the PTE group, the levels of D-dimer, BNP, TNF-?, and TNI were significantly elevated, and these changes were statistically significant (P<0.05). PCR analysis of ventricular myocardial tissue indicated significantly higher levels of BNP, TNF-?, and TNI mRNA in the PTE group than in the control group. These differences were statistically significant (P<0.05). The ST-T variations on the ECG of rabbits with acute PTE correlate strongly with the temporary changes in right heart volume caused by acute PTE. Keywords: Animal model of pulmonary embolism, B-type natriuretic peptide, Electrocardiogram, Pulmonary thromboembolism, Troponin I, Tumor necrosis factor-alpha.

• MeSH
• akutní nemoc MeSH
• elektrokardiografie * MeSH
• králíci MeSH
• modely nemocí na zvířatech * MeSH
• natriuretický peptid typu B krev   MeSH
• plicní embolie * patofyziologie   krev   MeSH
• TNF-alfa krev   metabolismus   genetika   MeSH
• troponin I krev   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Cardiac troponin I (cTnI) is an important biomarker of acute myocardial infarction (MI) in animals and human beings. Nevertheless, no immunohistochemical study has been reported about the pattern of myocardial cTnI egression in a minimally invasive model. The present study intended to establish a minimally invasive model of MI and to evaluate the distribution of cTnI. Twelve Mongrel dogs were divided into 2 groups (n = 6): experimental and sham-operated group. Three incisions were made on the left thoracic wall, left anterior descending (LAD) of coronary artery was identified and titanium nips were clamped by video-assisted thoracoscopy surgery (VATS). Series of electrocardiograms (ECG) and biochemical analyses of blood samples - oxidatively modified proteins (OMP), creatine kinase (CK), and cTnI were performed. Furthermore, Masson's trichrome staining was used to observe the histopathology of cardiac myocytes, while immunohistochemistry was done to observe cTnI egression from myocardium. ECG showed elevated ST-segment, whereas OMP, CK and cTnI level increased remarkably and declined to baseline subsequently in the model group throughout study period. Masson's trichrome staining of model group showed a large amount of collagen deposition in the fibrotic area as compared to control group. In immunohistochemical staining, no loss of cTnI staining was observed in non-necrotic myocardium, meanwhile, a great loss was observed in necrotic myocardium. An exception was the myocardium of cardiac apex, where loss of cTnI was visible even in non-necrotic myocardium. All these results revealed that loss of cTnI occurs not only in the necrotic myocardium but also in so-called non-necrotic myocardium of minimally invasive MI model through VATS.

• MeSH
• hrudní chirurgie video-asistovaná MeSH
• imunohistochemie metody   MeSH
• infarkt myokardu * metabolismus   patologie   MeSH
• kardiomyocyty metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• myokard chemie   metabolismus   patologie   MeSH
• psi MeSH
• troponin I analýza   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• psi MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem 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.

• 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

BACKGROUND: Cardiac troponins are routinely used as markers of myocardial damage. Originally, they were only intended for use in diagnosing acute coronary syndromes; however, we now know that raised serum troponin levels are not always caused by ischemia. There are many other clinical conditions that cause damage to cardiomyocytes, leading to raised levels of troponin. However, the specificity of cardiac troponins towards the myocardium is absolute. Our work focuses on mechanical damage to the myocardium and on monitoring the factors that raise the levels of cardiospecific markers after primo-implantation of a pacemaker with an actively fixed electrode. AIMS: (i) To determine whether the use of a primo-implanted pacemaker with an electrode system with active fixation will raise troponin levels over baseline. (ii) To assess whether troponin I elevation is dependent on procedure complexity. METHODS: We enrolled 219 consecutive patients indicated for pacemaker primo-implantation; cardiospecific marker values (troponin I, CKMB, myoglobin) were determined before the implantation procedure and again at 6- and 18-h intervals after the procedure. We monitored duration of cardiac skiascopy, number of attempts to place the electrode (active penetration into the tissue) and intervention range (single-chamber versus dual-chamber pacing), and we assessed the clinical data. RESULTS: The average age of the enrolled patients was 78.2 ± 8.0 years (median age, 80 years); women constituted 45% of the group. We implanted 128 dual-chamber and 91 single-chamber devices with an average skiascopic time of 38.6 ± 22.0 s (median, 33.5 s). Troponin I serum levels increased from an initial 0.03 ± 0.07 μg/L (median, 0.01) to 0.18 ± 0.17 μg/L (median, 0.13) and 0.09 ± 0.18 μg/L (median, 0.04) at 6 and 18 h, respectively. The differences were statistically significant (P < 0.001 or P < 0.001). We confirmed a correlation between troponin increase and duration of skiascopy (P < 0.001). We also demonstrated a correlation between increased troponin I and number of attempts to place a pacemaker electrode (penetration into the tissue) at 6 h (P < 0.001) post-implantation. CONCLUSION: We detected slightly elevated troponin I levels in patients with primo-implanted pacemakers using electrodes with active fixation. We demonstrated a direct correlation between myocardial damage (number of electrode penetrations into the myocardium) and troponin I elevation, as well as between complexity (severity) of the implantation procedure (indicated by prolonged skiascopy) and raised troponin I. The described phenomenon demonstrates the loss of the diagnostic role of troponin I early after pacemaker primo-implantation in patients with concomitant chest pain.

• MeSH
• biologické markery metabolismus   MeSH
• implantace protézy MeSH
• implantované elektrody MeSH
• kardiostimulátor * MeSH
• kreatinkinasa, forma MB metabolismus   MeSH
• lidé MeSH
• myoglobin metabolismus   MeSH
• pooperační komplikace krev   diagnóza   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• srdeční arytmie krev   terapie   MeSH
• troponin I metabolismus   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

PPARδ-dependent maintenance of inotropic function is mentioned as crucial for cardiomyocytes. However, change of PPARδ in endotoxins-induced cardiac dysfunction is still unclear. The present study is then designed to investigate the changes of PPARδ in rats showing LPS-induced cardiac dysfunction. In the in vivo experiments, adult Wistar rats were treated with intravenous injection of 10 mg/kg LPS for 6 h. The isolated heart determined in Langendorff apparatus and the hemodynamic analysis of rats used to measure the changes of cardiac function extra vivo and in vivo. We found that LPS decreased the cardiac contractility in isolated heart and lowered the hemodynamic dP/dtmax in rats. Also, this action of LPS was reversed by PPARδ agonist. In cultured neonatal rat cardiac cells incubated with LPS, the intracellular calcium concentration and troponin I phosphorylation were both reduced after the detection of intracellular calcium level and Western blotting analysis. PPARδ agonist also reversed both actions of LPS in cardiomyocyte. The obtained results suggest that LPS induced decreases in PPARδ expression and troponin I phosphorylation to result in acute heart failure similar to cardiac dysfunction in endotoxemia.

• Klíčová slova
• GW0742,
• MeSH
• endotoxemie * farmakoterapie   MeSH
• hemodynamika účinky léků   MeSH
• intracelulární "calcium-sensing" proteiny MeSH
• kardiomyocyty metabolismus   patologie   účinky léků   MeSH
• kontrakce myokardu účinky léků   MeSH
• krevní tlak účinky léků   MeSH
• krysa rodu rattus MeSH
• kultivační techniky MeSH
• lipopolysacharidy * aplikace a dávkování   MeSH
• novorozená zvířata MeSH
• potkani Wistar MeSH
• receptory aktivované proliferátory peroxizomů * účinky léků   MeSH
• srdeční selhání * patologie   MeSH
• statistika jako téma MeSH
• thiazoly aplikace a dávkování   MeSH
• troponin I metabolismus   MeSH
• western blotting MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH

AIMS: Delcasertib is a selective inhibitor of delta-protein kinase C (delta-PKC), which reduced infarct size during ischaemia/reperfusion in animal models and diminished myocardial necrosis and improved reperfusion in a pilot study during primary percutaneous coronary intervention (PCI) for ST elevation myocardial infarction (STEMI). METHODS AND RESULTS: A multicentre, double-blind trial was performed in patients presenting within 6 h and undergoing primary PCI for anterior (the primary analysis cohort, n = 1010 patients) or inferior (an exploratory cohort, capped at 166 patients) STEMI. Patients with anterior STEMI were randomized to placebo or one of three doses of delcasertib (50, 150, or 450 mg/h) by intravenous infusion initiated before PCI and continued for ∼2.5 h. There were no differences between treatment groups in the primary efficacy endpoint of infarct size measured by creatine kinase MB fraction area under the curve (AUC) (median 5156, 5043, 4419, and 5253 ng h/mL in the placebo, delcasertib 50, 150, and 450 mg/mL groups, respectively) in the anterior STEMI cohort. No treatment-related differences were seen in secondary endpoints of infarct size, electrocardiographic ST-segment recovery AUC or time to stable ST recovery, or left ventricular ejection fraction at 3 months. No differences in rates of adjudicated clinical endpoints (death, heart failure, or serious ventricular arrhythmias) were observed. CONCLUSIONS: Selective inhibition of delta-PKC with intravenous infusion of delcasertib during PCI for acute STEMI in a population of patients treated according to contemporary standard of care did not reduce biomarkers of myocardial injury.

• MeSH
• adjuvantní chemoterapie MeSH
• biologické markery metabolismus   MeSH
• dvojitá slepá metoda MeSH
• infarkt myokardu terapie   MeSH
• inhibitory proteinkinas aplikace a dávkování   MeSH
• intravenózní infuze MeSH
• koronární angioplastika metody   MeSH
• kreatinkinasa, forma MB metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• peptidy aplikace a dávkování   MeSH
• pilotní projekty MeSH
• plocha pod křivkou MeSH
• rozvrh dávkování léků MeSH
• senioři MeSH
• troponin I metabolismus   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

Vyšetřování vysoce senzitivních a pro myokard specifi ckých markerů nekrózy troponinů a nová „univerzální defi nice akutního infarktu myokardu“ má zajistit zpřesnění diagnostiky akutních koronárních syndromů i myokardiálních nekróz neaterosklerotického původu. Použití těchto nových zbraní však vyžaduje další znalosti o mechanismech uvolňování srdečních troponinů a zkušenosti s interpretací výsledků. Tyto poznatky a zkušenosti se teprve pozvolna dostávají do denní praxe. Jako akutní infarkty jsou nově diagnostikovány zcela minimální ischemické nekrózy, při kterých ale jejich nositelé již profi tují z razantní léčby a prevence aterosklerózy. Zároveň jsou mezi infarkty myokardu řazeny velmi časté drobné ischemické nekrózy podmíněné snížením nebo zvýšením potřeby okysličené krve, ale bez zřetelného postižení koronárního řečiště. I tyto stavy znamenají zvýšení kardiovaskulární morbidity a mortality, ale léčebné důsledky jsou jiné. Správné hodnocení narůstajícího množství stavů se zvýšením plazmatických koncentrací troponinů je proto velmi důležité. (Kap Kardiol 2011; 3: 42–45)

• MeSH
• biologické markery krev   MeSH
• infarkt myokardu diagnóza   klasifikace   MeSH
• lidé MeSH
• referenční hodnoty MeSH
• troponin I krev   metabolismus   MeSH
• troponin T krev   metabolismus   MeSH
• troponin krev   normy   MeSH
• Check Tag
• lidé MeSH

Chronic anthracycline cardiotoxicity is a feared complication of cancer chemotherapy. However, despite several decades of primarily hypothesis-driven research, the molecular basis of this phenomenon remains poorly understood. The aim of this study was to obtain integrative molecular insights into chronic anthracycline cardiotoxicity and the resulting heart failure. Cardiotoxicity was induced in rabbits (daunorubicin 3mg/kg, weekly, 10weeks) and changes in the left ventricular proteome were analyzed by 2D-DIGE. The protein spots with significant changes (p<0.01, >1.5-fold) were identified using MALDI-TOF/TOF. Key data were corroborated by immunohistochemistry, qRT-PCR and enzyme activity determination and compared with functional, morphological and biochemical data. The most important alterations were found in mitochondria - especially in proteins crucial for oxidative phosphorylation, energy channeling, antioxidant defense and mitochondrial stress. Furthermore, the intermediate filament desmin, which interacts with mitochondria, was determined to be distinctly up-regulated and disorganized in its expression pattern. Interestingly, the latter changes reflected the intensity of toxic damage in whole hearts as well as in individual cells. In addition, a marked drop in myosin light chain isoforms, activation of proteolytic machinery (including the proteasome system), increased abundance of chaperones and proteins involved in chaperone-mediated autophagy, membrane repair as well as apoptosis were found. In addition, dramatic changes in proteins of basement membrane and extracellular matrix were documented. In conclusion, for the first time, the complex proteomic signature of chronic anthracycline cardiotoxicity was revealed which enhances our understanding of the basis for this phenomenon and it may enhance efforts in targeting its reduction.

• MeSH
• 2D gelová elektroforéza MeSH
• antracykliny toxicita   MeSH
• daunomycin toxicita   MeSH
• echokardiografie MeSH
• extracelulární matrix účinky léků   metabolismus   MeSH
• imunohistochemie MeSH
• králíci MeSH
• malondialdehyd metabolismus   MeSH
• mitochondriální proteiny metabolismus   MeSH
• myokard metabolismus   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• proteomika MeSH
• srdeční komory účinky léků   metabolismus   MeSH
• srdeční selhání chemicky indukované   metabolismus   MeSH
• troponin I metabolismus   MeSH
• vimentin metabolismus   MeSH
• western blotting MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Kryptor system was proven to be a rapid, standard method for pregnancy-associated plasma protein A and proform eosinophilic major basic protein (PAPP-A/proMBP) complex detection in coronary artery disease (CAD). No age and/or gender differences in 51 controls and 110 stable coronary artery disease (SCAD) patients were found. SCAD patients did not differ from controls and no difference in PAPP-A/proMBP levels with regards to the number of affected vessels was found. In 21 unstable angina pectoris (UAP), in 35 without and 66 with ST elevation acute myocardial infarctions (NSTEMI, STEMI respectively) patients PAPP-A/proMBP levels were increased (P=0.004 and P<0.0005, respectively). PAPP-A/proMBP levels did not correlate with cardiac troponin I (cTnI) in STEMI and NSTEMI patients. PAPP-A/ proMBP increase was more frequent than cTnI (P=0.036) within the early phase of STEMI. In NSTEMI patients PAPP-A/proMBP positivity was present in 50 % of cTnI negative cases. Receiver operating characteristic (ROC) analysis revealed the highest diagnostic accuracy of PAPP-A/proMBP (0.919) in STEMI cTnI positive cases. The highest specificity/sensitivity PAPP-A/proMBP levels for particular acute coronary syndrome (ACS) types were 10.65-14.75 mIU/l. Combination of PAPP-A/proMBP with cTnI increases their diagnostic efficacy within the early phase of ACS. Our results suggest that PAPP-A/proMBP complex is involved in processes preceding vulnerable plaque development in ACS.

• MeSH
• akutní koronární syndrom diagnóza   krev   MeSH
• biologické markery krev   MeSH
• dospělí MeSH
• ELISA MeSH
• eozinofily - hlavní bazický protein analýza   diagnostické užití   metabolismus   MeSH
• hodnocení rizik MeSH
• imunoanalýza metody   přístrojové vybavení   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• nemoci koronárních tepen diagnóza   klasifikace   krev   MeSH
• neparametrická statistika MeSH
• proteinové prekurzory analýza   diagnostické užití   metabolismus   MeSH
• referenční hodnoty MeSH
• ROC křivka MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• senzitivita a specificita MeSH
• sexuální faktory MeSH
• studie případů a kontrol MeSH
• těhotenský plazmatický protein A analýza   diagnostické užití   metabolismus   MeSH
• troponin I analýza   diagnostické užití   metabolismus   MeSH
• věkové faktory MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH

• MeSH
• kardiomyopatie diagnóza   mortalita   patofyziologie   MeSH
• klinické laboratorní techniky metody   přístrojové vybavení   MeSH
• kosterní svaly MeSH
• lidé MeSH
• renální insuficience MeSH
• troponin I biosyntéza   krev   metabolismus   MeSH
• troponin T biosyntéza   krev   metabolismus   MeSH
• Check Tag
• lidé MeSH