Introduction: In pediatrics, ninety-eight percent of all chest pain complaints are non-cardiac in origin, with the leading cause being muscular skeletal pain. Of the two percent that are cardiac in origin, troponin levels are helpful in detecting cardiac muscle ischemia, most commonly present in myocardial infarction, pulmonary embolism, pericarditis, myocarditis, aortic dissection, heart failure, and cardiac contusion. There are multiple different troponin assays that detect troponin, usually using a two-site immunoezematic assay. Although values obtained may differ slightly between assays, there is not a statistically significant difference between assays. Several endogenous substances, such as rheumatoid factor, excess fibrin, alkaline phosphatase, and heterophile antibodies can cause statistically significant, though falsely increased troponin levels that do not rise and fall in the typical pattern seen in cardiac ischemia due to cross reactivity with the assays. We present the case of a fifteen-year-old male with chest pain and elevated troponins, but otherwise benign workup. It highlights the falsely elevated troponin levels seen with the cross-reactivity of heterophile antibodies and various troponin assays. Case Presentation: A 15-year-old male presents with a two-day history of intermittent, stabbing, 5/10 left sided chest pain, as well as substernal chest pressure that radiates to his left upper chest and shoulder. He is unable to identify any triggers of the pain or alleviating factors. Review of systems is negative for nausea, vomiting, diaphoresis, and shortness of breath. His past medical history is significant for pectus excavatum that has been corrected with Nuss bar procedure. He also reports being treated for strep pharyngitis two weeks prior. The patient presents to emergency department after having an irregular heart rate noted by the school nurse’s office. His vital signs are stable, and his physical exam is notable for a regular heart rate and rhythm. Pectus excavatum with well healed midline scar is present. A basic metabolic panel is normal. In the emergency department, serum troponins are elevated between 0.24-0.25 ng/ml (normal range 0.00-0.02), and a D-dimer is elevated at 500 ng/ml (normal range 0-230). Cardiology is consulted, and following an algorithm for chest pain in pediatric patients,1 a series of additional tests are performed. His electrocardiogram shows a normal sinus rhythm with minimal left axis deviation. Chest x-ray shows intact Nuss bars and is, otherwise, normal. Ventilation-Perfusion (VQ) scan is normal. An echocardiogram shows normal ventricular output and valvular function with an incidental finding of slight angulation of aortic arch with no significant gradient. Cardiology recommends trending troponins every 6 hours. A repeat EKG the following day shows normal sinus rhythm without evidence of ischemia or arrhythmia. Serial troponins remain elevated for the following 48 hours ranging 0.22-0.24 ng/ml. The patient denies any further cardiac symptoms despite the persistently elevated troponins, and he is discharged home with close follow-up with pediatric cardiology as well as a thirty-day looping event monitor. One week after discharge, in the cardiology clinic, troponin levels are still 0.23ng/ml. Creatine kinase MB level is obtained and is within normal limits. Due to persistently elevated troponins within a narrow range, a literature search is performed to determine if there are other causes for elevated troponins that neither rise nor fall. Several articles are found confirming cross reactivity between various antibodies and troponin assays that lead to falsely elevated troponin levels.2,3 Rheumatoid factor, antinucleic antibodies, and Epstein-Barr virus antibody titers are obtained. RF and ANA levels return within normal limits. However, EBV IgM levels are elevated , while EBV IgG levels are within normal limits, supporting the theory that the patient has a current infection of mononucleosis. The thirty day looping event monitor is uneventful, showing no dysrhythmia or ectopy. Serial echocardiograms continue to remain unchanged from the initial echo during the patient’s hospitalization. Serum samples are analyzed on four different troponin assays, and a vast variation in troponin levels is found, ranging from < 0.015 ng/ml (normal value) on the Siemens Vista/ cTnl to 0.23 ng/ml (significantly elevated) on Beckman Access/ AccuTnI+3. Serial dilution studies are performed on a Beckman Dxi800 instrument and reveal decreasing troponin values with increasingly diluted serum samples. Discussion: In pediatrics, ninety-eight percent of all chest pain complaints are non-cardiac in origin, with the leading cause being muscular skeletal pain.4 Of the two percent that are cardiac in origin, troponin levels are helpful in detecting cardiac muscle ischemia, most commonly present in myocardial infarct, pulmonary embolism, pericarditis, myocarditis, aortic dissection, heart failure, and cardiac contusion, over exertion, and rhabdomyolysis. Most troponin assays use a two-site immunoenzymatic assay. One study in 2016 found that various assays reported different troponin levels; however the 99th percentile cutoff values were in agreeance with each other.5 Heterophilie antibodies in the serum have been found to falsely elevate troponin levels due to cross-reactivity between the antibodies and troponin assays. Rheumatoid factor, fibrin, and alkaline phosphatase can also cause false positive results.2 Conclusions: Elevated troponins are commonly interpreted as a sign of myocardial injury that prompts an extensive cardiac evaluation. This case illustrates that a common pediatric illness, infection with Epstein-Barr virus, can cause a false elevation in serum troponins. Infectious mononucleosis, as well as autoimmune diseases, should be considered in the differential of patients who present with elevated troponins without an apparent cardiac source.

O quimioterápico doxorrubicina, pertencente à família das antraciclinas, é um dos agentes antineoplásicos mais utilizados na medicina veterinária, no tratamento de uma variedade de sarcomas e carcinomas. No entanto, o uso da doxorrubicina está associado à presença de toxicidade, envolvendo principalmente anormalidades hematológicas, gastrointestinais e cardiovasculares, podendo induzir uma cardiomiopatia irreversível. O objetivo deste trabalho foi avaliar estas manifestações tóxicas, bem como as alterações hematológicas, bioquímicas e eletrocardiográficas em 25 cães com diferentes neoplasias tratados com doxorrubicina (30 mg/m² a cada 21 dias por três doses). Além disso, buscou-se avaliar as troponinas cardíacas I e T como marcadores cardíacos para a detecção precoce de cardiomiopatia induzida pela quimioterapia. Amostras de sangue foram coletadas antes de cada administração de doxorrubicina, sete dias após (nadir) e um mês depois do término do tratamento. As toxicidades hematológicas e gastrointestinais foram as alterações mais frequentes, ocorrendo em 22 (88%) e 19 (76%) cães, respectivamente. Neutropenia severa ocorreu em 25% dos casos, enquanto que não foram observados casos de trombocitopenia severa. Os sinais mais comumente observados foram vômito, anorexia e diarréia, os quais foram responsáveis, em parte, pelo aparecimento de hipoalbuminemia e reduções nas concentrações séricas de potássio, cálcio e proteína total. Observou-se também aumento nas concentrações séricas de proteína C reativa o que, assim como a diminuição da albumina, deve ser consequência de uma resposta de fase aguda induzida pela administração da doxorrubicina. Sepse foi incomum, ocorrendo em menos de 2% dos casos, e nenhum animal veio a óbito por complicações da quimioterapia. Sinais clínicos de cardiomiopatia não foram observados, porém aumentos nas troponinas cardíacas I e T ocorreram em 18 (72%) e 5 (20%) cães, respectivamente. Todos os cães com altas concentrações de troponina cardíaca T também apresentavam altas concentrações de troponina cardíaca I. Arritmias foram detectadas em 15 (60%) animais, mas não houve correlação com o aumento das troponinas cardíacas séricas e a presença de arritmias. No entanto, os cães que desenvolveram complexos atriais e ventriculares prematuros no eletrocardiograma apresentaram altas concentrações das troponinas. Este estudo demonstrou a ocorrência de alterações hematológicas e gastrointestinais toleráveis em cães recebendo doxorrubicina como único agente quimioterápico. Além disso, as concentrações séricas de troponinas cardíacas I e T podem ser utilizadas na detecção precoce de lesão miocárdica induzida pela doxorrubicina em cães. / The anthracicline chemotherapic doxorubicin is one of the anticancer agents most used in veterinary medicine to treat a variety of sarcomas and carcinomas. However, doxorubicin is associated with several toxicities, including hematological, gastrointestinal and cardiac abnormalities, and it can induce cardiomyopathy in dogs. The purpose of this study was to evaluate these toxic manifestations, as well as hematological, biochemical and electrocardiographic alterations in 25 dogs with spontaneously occurring malignant tumors treated with doxorubicin (30 mg/m² each 21 days during three doses). Moreover, cardiac troponins I (cTnI) and T (cTnT) were evaluated to determine cardiac-specific markers for predict cardiomyopathy-induced by chemotherapy. Blood samples were collected before each doxorubicin administration, seven days after each dose (nadir) and one month after the end of therapy. Hematological and gastrointestinal toxicities were the most frequent abnormalities observed and occurred in 22 (88%) and 19 (76%) dogs, respectively. Severe neutropenia occurred in 25% of the animals, while severe thrombocytopenia was not observed. Vomiting, anorexia and diarrhea occurred frequently, and were responsible, in part, for the presence of hypoalbuminemia and decreases in potassium, calcium and total protein serum concentrations. Increases in C reactive protein were also observed, wich together with decreases in albumin, may be due to acute phase response induced by doxorubicin. The frequency of sepsis was less than 2% and any animal died because of therapy complications. Signs of cardiomyopathy were not observed, however, increases in serum concentrations of cTnI and cTnT were found in 18 (72%) and 5 (20%) dogs, respectively. All dogs with high cTnT had high cTnI concentrations. Arrhythmias were detected in 15 (60%) animals, and it was not correlated with increases in cardiac troponins. Those dogs that developed atrial and ventricular premature complexes in the electrocardiogram showed increases in cTnI concentrations. In conclusion, doxorubicin used as single agent produced tolerable hematological and gastrointestinal toxicosis. Furthermore, cTnI and cTnT measurement can be used for early detection of myocardial injury caused by doxorubicin chemotherapy in dogs.

O quimioterápico doxorrubicina, pertencente à família das antraciclinas, é um dos agentes antineoplásicos mais utilizados na medicina veterinária, no tratamento de uma variedade de sarcomas e carcinomas. No entanto, o uso da doxorrubicina está associado à presença de toxicidade, envolvendo principalmente anormalidades hematológicas, gastrointestinais e cardiovasculares, podendo induzir uma cardiomiopatia irreversível. O objetivo deste trabalho foi avaliar estas manifestações tóxicas, bem como as alterações hematológicas, bioquímicas e eletrocardiográficas em 25 cães com diferentes neoplasias tratados com doxorrubicina (30 mg/m² a cada 21 dias por três doses). Além disso, buscou-se avaliar as troponinas cardíacas I e T como marcadores cardíacos para a detecção precoce de cardiomiopatia induzida pela quimioterapia. Amostras de sangue foram coletadas antes de cada administração de doxorrubicina, sete dias após (nadir) e um mês depois do término do tratamento. As toxicidades hematológicas e gastrointestinais foram as alterações mais frequentes, ocorrendo em 22 (88%) e 19 (76%) cães, respectivamente. Neutropenia severa ocorreu em 25% dos casos, enquanto que não foram observados casos de trombocitopenia severa. Os sinais mais comumente observados foram vômito, anorexia e diarréia, os quais foram responsáveis, em parte, pelo aparecimento de hipoalbuminemia e reduções nas concentrações séricas de potássio, cálcio e proteína total. Observou-se também aumento nas concentrações séricas de proteína C reativa o que, assim como a diminuição da albumina, deve ser consequência de uma resposta de fase aguda induzida pela administração da doxorrubicina. Sepse foi incomum, ocorrendo em menos de 2% dos casos, e nenhum animal veio a óbito por complicações da quimioterapia. Sinais clínicos de cardiomiopatia não foram observados, porém aumentos nas troponinas cardíacas I e T ocorreram em 18 (72%) e 5 (20%) cães, respectivamente. Todos os cães com altas concentrações de troponina cardíaca T também apresentavam altas concentrações de troponina cardíaca I. Arritmias foram detectadas em 15 (60%) animais, mas não houve correlação com o aumento das troponinas cardíacas séricas e a presença de arritmias. No entanto, os cães que desenvolveram complexos atriais e ventriculares prematuros no eletrocardiograma apresentaram altas concentrações das troponinas. Este estudo demonstrou a ocorrência de alterações hematológicas e gastrointestinais toleráveis em cães recebendo doxorrubicina como único agente quimioterápico. Além disso, as concentrações séricas de troponinas cardíacas I e T podem ser utilizadas na detecção precoce de lesão miocárdica induzida pela doxorrubicina em cães. / The anthracicline chemotherapic doxorubicin is one of the anticancer agents most used in veterinary medicine to treat a variety of sarcomas and carcinomas. However, doxorubicin is associated with several toxicities, including hematological, gastrointestinal and cardiac abnormalities, and it can induce cardiomyopathy in dogs. The purpose of this study was to evaluate these toxic manifestations, as well as hematological, biochemical and electrocardiographic alterations in 25 dogs with spontaneously occurring malignant tumors treated with doxorubicin (30 mg/m² each 21 days during three doses). Moreover, cardiac troponins I (cTnI) and T (cTnT) were evaluated to determine cardiac-specific markers for predict cardiomyopathy-induced by chemotherapy. Blood samples were collected before each doxorubicin administration, seven days after each dose (nadir) and one month after the end of therapy. Hematological and gastrointestinal toxicities were the most frequent abnormalities observed and occurred in 22 (88%) and 19 (76%) dogs, respectively. Severe neutropenia occurred in 25% of the animals, while severe thrombocytopenia was not observed. Vomiting, anorexia and diarrhea occurred frequently, and were responsible, in part, for the presence of hypoalbuminemia and decreases in potassium, calcium and total protein serum concentrations. Increases in C reactive protein were also observed, wich together with decreases in albumin, may be due to acute phase response induced by doxorubicin. The frequency of sepsis was less than 2% and any animal died because of therapy complications. Signs of cardiomyopathy were not observed, however, increases in serum concentrations of cTnI and cTnT were found in 18 (72%) and 5 (20%) dogs, respectively. All dogs with high cTnT had high cTnI concentrations. Arrhythmias were detected in 15 (60%) animals, and it was not correlated with increases in cardiac troponins. Those dogs that developed atrial and ventricular premature complexes in the electrocardiogram showed increases in cTnI concentrations. In conclusion, doxorubicin used as single agent produced tolerable hematological and gastrointestinal toxicosis. Furthermore, cTnI and cTnT measurement can be used for early detection of myocardial injury caused by doxorubicin chemotherapy in dogs.

O quimioterápico doxorrubicina, pertencente à família das antraciclinas, é um dos agentes antineoplásicos mais utilizados na medicina veterinária, no tratamento de uma variedade de sarcomas e carcinomas. No entanto, o uso da doxorrubicina está associado à presença de toxicidade, envolvendo principalmente anormalidades hematológicas, gastrointestinais e cardiovasculares, podendo induzir uma cardiomiopatia irreversível. O objetivo deste trabalho foi avaliar estas manifestações tóxicas, bem como as alterações hematológicas, bioquímicas e eletrocardiográficas em 25 cães com diferentes neoplasias tratados com doxorrubicina (30 mg/m² a cada 21 dias por três doses). Além disso, buscou-se avaliar as troponinas cardíacas I e T como marcadores cardíacos para a detecção precoce de cardiomiopatia induzida pela quimioterapia. Amostras de sangue foram coletadas antes de cada administração de doxorrubicina, sete dias após (nadir) e um mês depois do término do tratamento. As toxicidades hematológicas e gastrointestinais foram as alterações mais frequentes, ocorrendo em 22 (88%) e 19 (76%) cães, respectivamente. Neutropenia severa ocorreu em 25% dos casos, enquanto que não foram observados casos de trombocitopenia severa. Os sinais mais comumente observados foram vômito, anorexia e diarréia, os quais foram responsáveis, em parte, pelo aparecimento de hipoalbuminemia e reduções nas concentrações séricas de potássio, cálcio e proteína total. Observou-se também aumento nas concentrações séricas de proteína C reativa o que, assim como a diminuição da albumina, deve ser consequência de uma resposta de fase aguda induzida pela administração da doxorrubicina. Sepse foi incomum, ocorrendo em menos de 2% dos casos, e nenhum animal veio a óbito por complicações da quimioterapia. Sinais clínicos de cardiomiopatia não foram observados, porém aumentos nas troponinas cardíacas I e T ocorreram em 18 (72%) e 5 (20%) cães, respectivamente. Todos os cães com altas concentrações de troponina cardíaca T também apresentavam altas concentrações de troponina cardíaca I. Arritmias foram detectadas em 15 (60%) animais, mas não houve correlação com o aumento das troponinas cardíacas séricas e a presença de arritmias. No entanto, os cães que desenvolveram complexos atriais e ventriculares prematuros no eletrocardiograma apresentaram altas concentrações das troponinas. Este estudo demonstrou a ocorrência de alterações hematológicas e gastrointestinais toleráveis em cães recebendo doxorrubicina como único agente quimioterápico. Além disso, as concentrações séricas de troponinas cardíacas I e T podem ser utilizadas na detecção precoce de lesão miocárdica induzida pela doxorrubicina em cães. / The anthracicline chemotherapic doxorubicin is one of the anticancer agents most used in veterinary medicine to treat a variety of sarcomas and carcinomas. However, doxorubicin is associated with several toxicities, including hematological, gastrointestinal and cardiac abnormalities, and it can induce cardiomyopathy in dogs. The purpose of this study was to evaluate these toxic manifestations, as well as hematological, biochemical and electrocardiographic alterations in 25 dogs with spontaneously occurring malignant tumors treated with doxorubicin (30 mg/m² each 21 days during three doses). Moreover, cardiac troponins I (cTnI) and T (cTnT) were evaluated to determine cardiac-specific markers for predict cardiomyopathy-induced by chemotherapy. Blood samples were collected before each doxorubicin administration, seven days after each dose (nadir) and one month after the end of therapy. Hematological and gastrointestinal toxicities were the most frequent abnormalities observed and occurred in 22 (88%) and 19 (76%) dogs, respectively. Severe neutropenia occurred in 25% of the animals, while severe thrombocytopenia was not observed. Vomiting, anorexia and diarrhea occurred frequently, and were responsible, in part, for the presence of hypoalbuminemia and decreases in potassium, calcium and total protein serum concentrations. Increases in C reactive protein were also observed, wich together with decreases in albumin, may be due to acute phase response induced by doxorubicin. The frequency of sepsis was less than 2% and any animal died because of therapy complications. Signs of cardiomyopathy were not observed, however, increases in serum concentrations of cTnI and cTnT were found in 18 (72%) and 5 (20%) dogs, respectively. All dogs with high cTnT had high cTnI concentrations. Arrhythmias were detected in 15 (60%) animals, and it was not correlated with increases in cardiac troponins. Those dogs that developed atrial and ventricular premature complexes in the electrocardiogram showed increases in cTnI concentrations. In conclusion, doxorubicin used as single agent produced tolerable hematological and gastrointestinal toxicosis. Furthermore, cTnI and cTnT measurement can be used for early detection of myocardial injury caused by doxorubicin chemotherapy in dogs.

Luminescent quantum dot (QD) based probes have gained significance in the last decade for optical imaging of cells, tissues and in bioassays as alternatives to conventional organic fluorophores. The main objective of my PhD dissertation was to develop luminescent quantum dot based bioassays for real time monitoring of enzyme activity and simultaneous detection of several biomarkers. The quantum dot based bioassays developed will be potential tools in identification and diagnosis of several ailments that interfere with normal living conditions of human beings. In Chapter 2 new liposome encapsulated quantum dot based fluorescence resonance energy transfer (FRET) probes have been fabricated and characterized for monitoring the enzymatic activity of phospholipase A 2. The probes were able to detect the enzyme activity as low as 0.0075 U/mL (PLA2 = 1500 U/mg) in 30 min. Further these FRET probes were also used to screen the inhibition efficiencies of phospholipase A2 inhibitors. Chapter 3 focuses on the first time synthesis and characterization of liposome encapsulated InP/ZnS quantum dots while preserving the integrity of the liposomes. Results from the experiments to assess photostability and effect of pH on the optical properties of InP/ZnS QD-liposomes showed greater advantages over InP/ZnS quantum dots demonstrating their utility as a potential tool in several biological applications such as bio imaging, bioassays and in immunoassays. Chapter 4 discusses the development of fluorescence based immunoassay for simultaneous detection of the cardiac biomarkers troponin T and troponin I using CdSe/ZnS quantum dots. The assay achieved a detection limit was 0.1 pg/mL for both biomarkers troponin xi T and I. The method was highly specific for the both the biomarkers with no observed cross reactivity. The multiplex assay was able to detect two biomarkers simultaneously that will yield a high throughput diagnostic tool for heart attack. A similar method discussed as above was used in chapter 5 for the simultaneous detection of atherosclerosis biomarkers. The detection limits achieved in this study are comparable to the detection limits of the biomarkers reported so far. Incorporation of QDs in silica beads before conjugation to antibodies might improve detection limits that will also improve risk assessment.

O objetivo desse estudo foi verificar as repercussões clínicas e na capacidade cardiopulmonar, resultantes das alterações agudas morfofuncionais cardíacas e dos marcadores de injúria miocárdica após a realização de uma maratona, assim como a influência dos polimorfismos da ECA e BNP. Para tanto, 74 maratonistas, que participariam da XIX Maratona Internacional de São Paulo 2013 foram submetidos aos seguintes procedimentos: anamnese, exame físico, avaliação física, ecocardiograma, eletrocardiograma, bem como um teste cardiopulmonar. 24 horas antes da maratona, foi realizada uma coleta de sangue, em jejum. No terceiro momento, imediatamente antes da maratona, os atletas foram submetidos a medida de peso e bioimpedância elétrica a fim de caracterizar a quantidade de água corporal. Imediatamente após a maratona, os atletas foram submetidos a medida de peso, bioimpedância elétrica, coleta de sangue e ecocardiograma. 24 e 72 horas após a maratona, os atletas foram submetidos a coleta de sangue. No sétimo e último momento, entre três e quinze dias apos a maratona, novamente um teste cardiopulmonar. Os principais resultados foram: a) Houveram alterações estatisticamente significativas em todos os marcadores de injúria miocárdica no período após a maratona, sem retorno aos valores basais 72 horas após a maratona, exceto para troponina; b) Não houve correlação linear entre os marcadores relacionados a isquemia e morte celular e o BNP. Porém, houve correlação cúbica entre o BNP e a troponina, além da correlação entre todos os marcadores de injúria relacionados a isquemia e morte, com efeito baixo deles na troponina, na análise de regressão linear; c) Houve influência da idade e experiência de treinamento na liberação de troponina e BNP, e da intensidade de realização da prova nos outros marcadores; d) Houve influência das características ecocardiográficas na liberação de troponina; e) O aumento das capacidades pulmonares na espirometria de repouso, assim como na ventilação do 2º limiar e pico no teste cardiopulmonar correlacionaram-se significativamente com a queda de hemoglobina ocorrida nos dias após a maratona; f) A redução dos níveis de hemoglobina e hematócrito nos maratonistas, 24 e 72 horas após a maratona, caracterizam a anemia do atleta; g) Não houve correlação entre os polimorfismos da ECA e do BNP e as características ecocardiográficas relacionadas ao coração de atleta, porém há correlação com a liberação de BNP após a maratona / The aims of this study was to verify the clinical implications and in the cardiopulmonary capacity resulting from acute cardiac morphofunctional changes and myocardial injury markers after a marathon, as well as the influence of ACE and BNP polymorphisms. Therefore, 74 marathon runners, which participate in the XIX International Marathon of São Paulo in 2013, underwent the following procedures: anamnesis, physical examination, fitness assessment, echocardiogram, electrocardiogram and a cardiopulmonary exercise testing. 24 hours before the marathon, a blood collect was held. Immediately before the marathon, athletes underwent measurement of weight and bioelectrical impedance to characterize the amount of body water. Immediately after the marathon, athletes underwent weight measurement, electrical impedance, blood collect and echocardiogram. 24 and 72 hours after the marathon athletes collected blood. In the seventh and final time between three and fifteen days after the marathon, a cardiopulmonary exercise test was performed. The main results were: a) There were statistically significant changes in all myocardial injury markers in the period after the marathon, which didn\'t return to basal values 72 hours after marathon, except to cardiac troponins; b) There was no linear correlation between the marker related to ischemia and cell death and the BNP. However, there cubic correlation between BNP and troponin, in addition to the correlation between all markers of injury related to cellular ischemia and death, with low effect on troponin in the linear regression analysis; c) Age and training experience affected the release of troponin and BNP, and intensity affected the others markers; d) There was influence of echocardiographic features in the release of troponin; e) The increase in lung capacity in spirometry as well as ventilation of the second threshold and peak in the cardiopulmonary test were significantly correlated with the decrease in haemoglobin occurred after marathon; f) The reduction of haemoglobin and haematocrit levels in marathon runners, 24 and 72 hours after marathon called athletes anaemia; g) There was no correlation between ACE and BNP polymorphisms and echocardiographic features related to the athlete\'s heart, but correlation with the release of BNP after marathon

O objetivo desse estudo foi verificar as repercussões clínicas e na capacidade cardiopulmonar, resultantes das alterações agudas morfofuncionais cardíacas e dos marcadores de injúria miocárdica após a realização de uma maratona, assim como a influência dos polimorfismos da ECA e BNP. Para tanto, 74 maratonistas, que participariam da XIX Maratona Internacional de São Paulo 2013 foram submetidos aos seguintes procedimentos: anamnese, exame físico, avaliação física, ecocardiograma, eletrocardiograma, bem como um teste cardiopulmonar. 24 horas antes da maratona, foi realizada uma coleta de sangue, em jejum. No terceiro momento, imediatamente antes da maratona, os atletas foram submetidos a medida de peso e bioimpedância elétrica a fim de caracterizar a quantidade de água corporal. Imediatamente após a maratona, os atletas foram submetidos a medida de peso, bioimpedância elétrica, coleta de sangue e ecocardiograma. 24 e 72 horas após a maratona, os atletas foram submetidos a coleta de sangue. No sétimo e último momento, entre três e quinze dias apos a maratona, novamente um teste cardiopulmonar. Os principais resultados foram: a) Houveram alterações estatisticamente significativas em todos os marcadores de injúria miocárdica no período após a maratona, sem retorno aos valores basais 72 horas após a maratona, exceto para troponina; b) Não houve correlação linear entre os marcadores relacionados a isquemia e morte celular e o BNP. Porém, houve correlação cúbica entre o BNP e a troponina, além da correlação entre todos os marcadores de injúria relacionados a isquemia e morte, com efeito baixo deles na troponina, na análise de regressão linear; c) Houve influência da idade e experiência de treinamento na liberação de troponina e BNP, e da intensidade de realização da prova nos outros marcadores; d) Houve influência das características ecocardiográficas na liberação de troponina; e) O aumento das capacidades pulmonares na espirometria de repouso, assim como na ventilação do 2º limiar e pico no teste cardiopulmonar correlacionaram-se significativamente com a queda de hemoglobina ocorrida nos dias após a maratona; f) A redução dos níveis de hemoglobina e hematócrito nos maratonistas, 24 e 72 horas após a maratona, caracterizam a anemia do atleta; g) Não houve correlação entre os polimorfismos da ECA e do BNP e as características ecocardiográficas relacionadas ao coração de atleta, porém há correlação com a liberação de BNP após a maratona / The aims of this study was to verify the clinical implications and in the cardiopulmonary capacity resulting from acute cardiac morphofunctional changes and myocardial injury markers after a marathon, as well as the influence of ACE and BNP polymorphisms. Therefore, 74 marathon runners, which participate in the XIX International Marathon of São Paulo in 2013, underwent the following procedures: anamnesis, physical examination, fitness assessment, echocardiogram, electrocardiogram and a cardiopulmonary exercise testing. 24 hours before the marathon, a blood collect was held. Immediately before the marathon, athletes underwent measurement of weight and bioelectrical impedance to characterize the amount of body water. Immediately after the marathon, athletes underwent weight measurement, electrical impedance, blood collect and echocardiogram. 24 and 72 hours after the marathon athletes collected blood. In the seventh and final time between three and fifteen days after the marathon, a cardiopulmonary exercise test was performed. The main results were: a) There were statistically significant changes in all myocardial injury markers in the period after the marathon, which didn\'t return to basal values 72 hours after marathon, except to cardiac troponins; b) There was no linear correlation between the marker related to ischemia and cell death and the BNP. However, there cubic correlation between BNP and troponin, in addition to the correlation between all markers of injury related to cellular ischemia and death, with low effect on troponin in the linear regression analysis; c) Age and training experience affected the release of troponin and BNP, and intensity affected the others markers; d) There was influence of echocardiographic features in the release of troponin; e) The increase in lung capacity in spirometry as well as ventilation of the second threshold and peak in the cardiopulmonary test were significantly correlated with the decrease in haemoglobin occurred after marathon; f) The reduction of haemoglobin and haematocrit levels in marathon runners, 24 and 72 hours after marathon called athletes anaemia; g) There was no correlation between ACE and BNP polymorphisms and echocardiographic features related to the athlete\'s heart, but correlation with the release of BNP after marathon

Background: Diagnosis of acute coronary syndromes (ACS) in the Emergency Department (ED) is a topical and contentious issue. Current diagnostic techniques rely on hospital admission for troponin testing. Only a minority of those admitted prove to have ACS while unacceptable proportions of those discharged have unrecognised ACS. Aims: We aimed to evaluate the diagnostic and prognostic value of individual clinical findings and novel biomarkers in ED patients with suspected cardiac chest pain. We then aimed to derive a clinical decision rule (CDR) to potentially enable safe, immediate discharge of a proportion of patients from the ED while risk stratifying others to facilitate triage to an appropriate level of in-patient care. Methods: We recruited patients who presented to the ED with suspected cardiac chest pain. Variables that have previously been shown to predict diagnosis of acute myocardial infarction (AMI) or to predict outcome were prospectively recorded. Blood was drawn at presentation for levels of eight biomarkers. Patients underwent 12-hour troponin testing and were followed up for the composite primary outcome of AMI, death or urgent coronary revascularisation for six months. Variables that were univariate predictors (p<0.05) of outcome were entered into a multivariate analysis using recursive partitioning. Results: While many clinical findings and levels of all eight novel biomarkers were found to be significant predictors of outcome, none could be used individually to confirm or exclude ACS in the ED. We derived a nine-point CDR that combined clinical findings with biomarker levels to effectively stratify patients into four risk groups. 14.2% of patients were identified as being at ‘no risk’ and had a 0.0% outcome rate. The rule performed significantly better than two commonly used risk scores and may improve on triage decisions made in actual clinical practice. Conclusion: ACS remains a difficult diagnosis to confidently confirm or refute in the ED. Our CDR may help to avoid unnecessary hospital admissions while improving on triage decisions made for the remaining in-patients. Prospective validation of our findings is warranted.

L’activité physique régulière est bénéfique pour la santé cardiovasculaire. Cependant, destravaux ont rapporté des dysfonctions cardiaques après des exercices physiques prolongés (EPP) tels que les marathons ou les triathlons longue distance type "Ironman". Ces dysfonctions sont souvent associées à des dommages myocardiques. Récemment, des études échocardiographiques ont suggéré que ces dysfonctions étaient associées à des baisses de contractilité et de relaxation myocardiques.Toutefois, l’atteinte myocardique après un EPP reste à ce jour controversée et les mécanismes sousjacents de ces dysfonctions demeurent inconnus. Dans ce contexte, le but de ce travail de doctorat a été de vérifier la diminution de contractilité et/ou de relaxation du myocarde après un EPP ii) d’évaluer l’implication de la voie ß-adrénergique et du stress oxydant dans l’altération de la fonction cardiaque.Pour cela, une première approche clinique, basée sur l’utilisation de l’échocardiographie cardiaque haute résolution (et plus particulièrement une technique de pointe, le "Speckle TrackingEchocardiography") nous a permis d’appréhender la fonction myocardique par l’intermédiaire de l’évaluation des déformations et de la torsion du ventricule gauche pendant le cycle cardiaque. Une deuxième approche fondamentale, chez l’animal, nous a permis d’évaluer la fonction cardiaque après un EPP chez le rat au niveau de l’organe entier et de l’organe isolé dans des conditions basale et de stress (ß-adrénergique). Des investigations complémentaires ont été réalisées sur le tissu myocardique pour évaluer le stress oxydant (GSH/GSSG, MDA) et des marqueurs de dommages cellulaires cardiaques (troponines I) après avoir bloqué la NAD(P)H oxydase (Nox), enzyme fortement impliquée dans la production d’espèces réactives dérivées de l’oxygène au niveau cardiaque. Les résultats de ces travaux montrent clairement, chez l’Homme et l’animal, des baisses de contractilité et de relaxation myocardiques associées à une augmentation des marqueurs de dommages cellulaires cardiaques après un EPP. Alors que la voie ß-adrénergique ne semble pas être impliquée dans ces dysfonctions, nos résultats indiquent que le stress oxydant joue un rôle majeur, puisque lorsque la Nox est bloquée, la fonction cardiaque est majoritairement restaurée après l’EPP. / Regular physical activity is beneficial for cardiovascular health. However, recentstudies have uncovered the presence of cardiac dysfunctions following prolonged physical exercise(PPE), such as marathon racing, or long-distance triathlons like the “Ironman”. These cardiacdysfunctions are often associated with damage at the myocardial level. Recently, someechocardiographic studies suggested that these dysfunctions were linked to a diminished myocardialcontractility and relaxation capacity. Nonetheless, the specific impact of PPE on myocardial propertiesremains controversial, and the mechanisms underlying these dysfunctions are thus far unknown.Therefore, within this context, the objectives of this PhD research were to i) verify the purporteddecrease in myocardial contractility and relaxation capacity following PPE, and ii) evaluate the rolesof the B-adrenergic pathway and oxidative stress in the alteration of cardiac function. In order toexplore this adequately, two different approaches were used. Firstly, a clinical approach wasemployed, based on the use of high resolution echocardiography (or more specifically, a leading edgetechnique known as Speckle Tracking Echocardiography), and allowed us to characterise myocardialfunction via the evaluation of left ventricular strain and torsion during a cardiac cycle. The secondfundamental approach, using an animal model, allowed us to evaluate cardiac function following PPEin rats; at a whole organ (in vivo) level and at an isolated organ (ex vivo) level, during both resting andstress (ß-adrenergic) conditions. Complementary investigations were conducted on myocardial tissueto evaluate oxidative stress (GSH/GSSG,MDA) and markers of myocardial damage (troponin I), afterhaving blocked NAD(P)H oxidase (Nox); an enzyme strongly involved in the production of oxidativestress at the cardiac level. Our findings clearly demonstrate, in both humans and animals, a decrease inmyocardial contractility and relaxation capacity, associated with an increase in markers of myocardialdamage, following PPE. Whilst the ß-adrenergic pathway does not appear to be involved in thesedysfunctions, our results indicate that oxidative stress plays a major role, since cardiac function isrestored following PPE when the Nox is blocked.