Com o objetivo de avaliar se o exercício físico prolongado causa alterações miocárdicas em eqüinos de enduro e se estas alterações cardíacas têm influência no desempenho dos animais durante as provas, avaliaram-se 30 cavalos, divididos em três grupos de dez animais cada, sendo G1 composto por animais que percorreram distâncias acima de 100 km, G2 por animais que percorreram distâncias menores de 100 km e G3 por animais desqualificados por alterações metabólicas. Os animais foram avaliados em três momentos distintos, T0 (pré-exercício, em repouso), T1 (entre 30 e 60 minutos após o exercício) e T2 (entre 90 e 120 minutos pós-exercício). Realizaram-se o exame físico e o exame ecocardiográfico, além de colheita de amostras de sangue para determinação de troponina I cardíaca sérica e outras provas bioquímicas. Não houve diferença nos valores de troponina I cardíaca entre os diversos grupos nem nos diferentes tempos. Observou-se diminuição dos valores do diâmetro interno do ventrículo esquerdo em diástole e aumento de espessura de septo interventricular pós-exercício. Não houve diferença nos índices funcionais cardíacos e houve manutenção do débito cardíaco por aumento da freqüência cardíaca. Estas alterações ecocardiográficas de pequena magnitude foram mais evidentes nos animais desqualificados por alterações metabólicas e não parecem estar relacionadas a injúria miocárdica e sim secundárias a outras condições orgânicas. Conclui-se que o exercício físico prolongado não leva a injúrias cardíacas severas em cavalos de enduro. / With the purpose of evaluating myocardial alterations caused by prolonged physical exercise and whether these alterations influence the endurance horses\' performance during the races, 30 horses were evaluated, divided into three groups of ten horses each, being G1 composed by animals that performed distances of more than 100 km, G2 by animals that performed distances of less than 100 km and G3 by animals disqualified by metabolic alterations. The horses were evaluated in three distinct moments, T0 (pre-exercise, at rest), T1 (between 30 and 60 minutes post-exercise) and T2 (between 90 and 120 minutes post-exercise). Physical and echocardiographic examinations and else blood sample collection for the determination of cardiac troponin I and other biochemical tests were done. There was no difference in cardiac troponin I values neither between the various groups, nor between the moments. There was a decrease in the post-exercise values of the diastolic left ventricle internal diameter and an increase in the post-exercise values of the interventricular septal thickness. There was no difference in the cardiac functional indexes and the cardiac output was maintainded by augmentation of the heart rate. These minor echocardiographic alterations were more evident in the animals that were disqualified by metabolic alterations, and they don\'t seem to be related to myocardial injury, but secondary to other organic conditions. Based on these results, prolonged physical exercise doesn\'t seem to cause severe cardiac injuries in endurance horses.

Ao contrário do homem, as cardiopatias de natureza hipóxica/isquêmica são pouco relatadas nos cães. Raros são os relatos de infarto agudo do miocárdio (IAM) nesses espécimes; entretanto, existem achados eletrocardiográficos que indicam hipóxia/isquemia miocárdica, como os desníveis (infra e supra) do segmento ST. Com o intuito de constatar algum dano nas células do miocárdio em condições de má perfusão, utilizaram-se 38 cães, dos quais 20 com traçados eletrocardiográficos normais e 18 com desníveis (infra e supra) do segmento ST, na derivação DII, velocidade de 50 mm/s e sensibilidade N. Nos animais normais (grupo 1), a dosagem sérica da enzima creatinafosfoquinase isoenzima MB (CK-MB) e da troponina I (cTnI) destinou-se à obtenção dos valores de referência (em ng/mL). Estes valores de referência foram confrontados com os obtidos de cães portadores de desnível (grupo 2), permitindo confirmar ou não a injúria miocárdica. Em relação à CK-MB, os cães do grupo 1 apresentaram média de 0,54 ng/mL e desvio-padrão de 0,89 ng/mL e os do grupo 2 apresentaram média de 0,44 ng/mL e desvio-padrão de 1,106 ng/mL. A média e o desvio-padrão foram, respectivamente, de 0,16 ng/mL e 0,110 ng/mL e de 0,20 ng/mL e 0,111 ng/mL, nos grupos 1 e 2. Houve 18 valores nulos de CK-MB, igualmente distribuídos entre ambos os grupos. O grupo 1 apresentou três valores nulos para cTnI. Houve diferença marcante em relação à idade, sendo o grupo 1 constituído por animais, preponderantemente, abaixo de 7 anos; o contrário ocorreu no grupo 2. São significativas, ao nível de significância de 5%, as associações da variável CK-MB com as variáveis idade, massa e CK-T (creatinafosfoquinase total) no grupo 1, e com a variável CK-T no grupo 2. A variável cTnI não apresentou evidências de associação, ao nível de significância de 5% , com as variáveis idade, massa, CK-T e nível sérico de potássio, para cada um dos níveis da variável grupo. Tanto para a variável CK-MB quanto para a cTnI, não houve diferenças significativas, ao nível de 5%, entre os grupos 1 e 2. Conclui-se que é possível a utilização do \"kit\" de ensaio imunométrico quimioluminescente humano para a espécie canina e que a hipóxia/isquemia, revelada pelo desnível do segmento ST, não acarreta dano miocárdico, ou que este é mínimo. / Although very often in men, hypoxic and ischemic heart diseases are poorly documented in dogs. There are few reports of acute myocardial infarction (AMI) in this species. However, some electrocardiographic findings may suggest myocardium hypoxia/ischemia, like ST segment elevation or depression. In order to investigate myocardial cells injury in poor perfusion conditions, 38 dogs, being 20 with normal electrocardiogram and 18 with ST segment elevation or depression in lead II, at a paper speed of 50 mm/sec and N sensibility (1 mV = 1cm), were included. Serum measurement of creatinephosphokinase isoenzyme MB (CK-MB) enzym and troponin I (cTnI) in normal dogs (group 1) determined reference values (in ng/ml). These values were compared to those obtained in dogs with deviation (group 2), which allowed confirmation or not of myocardial injury. CK-MB mean values obtained from dogs in groups 1 and 2 was 0,54 ng/mL (SD±0,54 ng/mL) and 0,44 ng/mL (SD±1,106), respectively. Mean cTnI values in groups 1 and 2 was 0,16 ng/mL (SD±0,110 ng/mL) and 0,20 ng/mL (SD±0,111 ng/mL) respectively. Three cTnI null values were found in group 1. There was a marked difference concerning to age, being group 1 composed, mainly, by animals ageing under 7 years, on the contrary of group 2. At a significance level of 5%, was significant the relation of CK-MB with age, mass and total creatinephosphokinase (CK-T) in group 1 and with CK-T in group 2. There is no relation, at a significance level of 5%, of cTnI with age, mass, CK-T or serum potassium concentration, for each level of group variable. Both CK-MB and cTnI variables showed no difference, at 5% level, between groups 1 and 2. In conclusion, it is possible to use the human chemiluminescent immunometric assay kit in canine species and that hypoxia/ischemia revealed by ST segment deviation does not mean significant myocardium injury.

Approximately 30% of people admitted to ICU in the UK have co-existing cardiovascular disease (CVD), and this may rise as life-expectancy increases. Patients with CVD have impaired compensatory mechanisms to enable maximum oxygen delivery to the tissues in the event of critical illness, which itself increases global oxygen demand, further stressing the heart. This is exacerbated by tachycardia and hypotension, which may relatively reduce blood flow to the coronary arteries, and catecholamines which increase myocardial oxygen demand. The myocardium extracts 75% of the oxygen supplied by the coronary arteries at rest, and atheroma-related flow limitation further compromises myocardial oxygen delivery. However, the diagnosis of acute coronary syndrome in critical illness is not straightforward, due to patient inability to communicate symptoms, non-specific ECG changes, and poorly understood cardiac biomarker troponin elevation. My overall hypothesis is that patients with CVD benefit from increased oxygen delivery to the myocardium during critical illness. A focus is the importance of anaemia. The aims of the studies presented in this thesis are (i) to systematically review the literature regarding blood transfusion thresholds specifically in patients with CVD; (ii) to explore the association between Troponin I (TnI) within 24 hours of ICU admission and hospital mortality (iii) to describe and quantify the dynamics of TnI in patients with CVD during the first ten days after ICU admission; and (iv) to define myocardial infarction in the context of critical illness. I have performed a systematic review and meta-analysis of randomised controlled trials comparing a restrictive with liberal transfusion threshold and that included patients with CVD. In total, 11 trials enrolling patients with CVD (n=3033) were included for meta-analysis (restrictive n=1514, liberal=1519). The pooled risk ratio for the association between a restrictive transfusion threshold and 30 day mortality was 1.15 (95% CI 0.88 to 1.50, p=0.50, I2=14%). The risk of acute coronary syndrome in patients managed with restrictive compared with liberal transfusion was increased (nine trials, risk ratio 1.78, 95% CI 1.18 to 2.70, p=0.0, I2=0%). In contrast to broader literature supporting restrictive thresholds, our systematic review shows that a restrictive transfusion threshold of less than 80g/l may not be safe in patients with co-existing CVD, and highlights the variability in diagnostic definitions of ACS and the potential for ascertainment bias in transfusion trials. I undertook a retrospective cohort study in two independently collected cohorts of general ICU patients who had TnI measured within 24 hours of ICU admission. Importantly, the majority of TnI samples were collected routinely rather than for clinical indications. We used the Abbott ARCHITECT Stat assay (limit of detection 0.01mcg/l. We performed multivariable regression, adjusting for components of the APACHE II model. We derived the risk prediction score from the multivariable model with TnI. TnI was associated with all cause hospital mortality (OR per doubling TnI 1.16, 95% CI 1.13 to 1.20, p < 0.001) which persisted after adjustment for APACHE II model components (OR TnI 1.05, 95% CI 1.01 to 1.09, p=0.003). TnI correlated highly with the Acute Physiological Score component of APACHE II (r=0.39), suggesting that TnI release may be largely explained by acute physiological stress. Addition of TnI to the APACHE II model did not improve the performance of the risk prediction model and we would not advocate the adoption of a routine single troponin sample at admission. I designed, set up, and recruited 279 patients to a prospective cohort study TROPonin I in Cardiovascular patients in CriticAL care (TROPICCAL, UKCRN 19253) in 11 UK centres. The aims were to (i) determine the incidence of Myocardial Injury and Infarction, defined by the Third Universal Definition of Myocardial Infarction; (ii) explore factors associated with Injury and Infarction from multivariable analyses; and (iii) explore the relationship between Injury/Infarction and outcome in unadjusted and adjusted analyses. We recorded baseline characteristics, and took daily hs-TnI for ten days after ICU admission, severity of illness measures and ECGs for 5 days. There was a wide range of peak TnI (med 114ng/l (min 3, Q1 27, Q3 412, max 58820ng/l)) and a high prevalence of myocardial injury on systematic screening: 71% of patients had peak TnI greater than the sex-specific diagnostic threshold ('Injury'), and 24% had peak TnI greater than the sex-specific diagnostic threshold and dynamic changes on ECG consistent with ischaemia ('Infarction'). TnI consistently showed a rise-and-fall pattern consistent with an acute myocardial 'hit' rather than persisting injury, which peaked early during ICU stay. Importantly, only 12 (4.4%) patients were diagnosed with MI by the clinicians looking after the patients. Independent predictors of peak TnI in the preceding 24 hours were SOFA score, dynamic ECG ischaemia, lactate, haemoglobin, and age. The lack of association with CRP (representing systemic inflammation), with stronger association with lactate (representing inadequate perfusion/oxygen supply), Hb and ECG ischaemia support the conjecture that injury results in part from an acute ischaemic hit in this population. Patients with Infarction had similar baseline demographics to patients with Injury, but had higher peak TnI concentrations, and higher hospital and six month mortality (Figure 2). This supports the importance of including systematic assessment of dynamic ECG changes in the myocardial injury 'construct' in ICU. My work has shown an increased risk of ACS in patients with CVD randomised to restrictive transfusion thresholds. TnI elevation is prevalent in general ICU patients, and is independently associated with hospital mortality. A systematic approach to the detection of myocardial injury in critically ill patients with co-existing CVD who are unable to communicate symptoms, can identify a high risk population who have poorer survival than patients with no injury. Markers of ischaemia are more associated with TnI rise than markers of inflammation, supporting the hypothesis that myocardial injury in this population is at least in part due to oxygen supply-demand imbalance 'myocardial infarction'. From this work, I would recommend (i) a more liberal transfusion threshold of at least 80g/l in patients with coexisting CVD; (ii) systematic use of sequential ECGs in ICU to screen for myocardial injury in 'at risk' patients; and (iii) manipulation of physiological parameters such as anaemia, hypotension and tachycardia should be considered for patients with dynamic ECG changes plus troponin increase consistent with Infarction. Future research should include 'precision medicine' trials in the substantial cohort of ICU patients with co-existing CVD to explore whether interventions that increase myocardial oxygen supply and/or treat infarction alter outcomes.

Em todo o mundo, milhões de pacientes são atendidos em emergências por apresentarem dor torácica de início aguda, mas apenas uma parcela deve-se a síndrome coronariana aguda (SCA). Em situações como essa é de extrema importância distinguir quando a dor torácica é devido à isquemia do miocárdio, pois esta é de alto risco e o início do tratamento deve ser imediato. Novos biomarcadores são necessários para auxiliar no diagnóstico e conduta clínica a ser tomada diante de situações de emergência como esta. Recentemente a quantificação de troponinas através de ensaios ultrassensíveis tem sido amplamente utilizado para diagnósticos e prognóstico de isquemia cardíaca, porém esses ensaios não tiveram seus valores de referências estabelecidos e validados para diversas situações clínicas. O presente estudo identificou a troponina I cardíaca nitrada como um novo biomarcador para isquemia cardíaca. Através de experimentos de imunoluorecência, foi possível colocalizar a marcação de troponina I cardíaca e nitrotirosina em modelos celulares e murinos de isquemia cardíaca, sugerindo assim que a troponina I cardíaca é nitrada. A partir do soro de modelos porcinos de isquemia, foi realizado o enriquecimento de proteínas nitradas por imunoprecipitação seguido da identificação da troponina I cardíaca por western blot. Dessa maneira foi possível identificar a troponina I cardíaca nitrada no soro poucos minutos após o evento x isquêmico, a qual permaneceu circulante por até 24 horas. Nessas mesmas amostras outros biomarcadores de isquemia como CKMB, Troponina I e Troponina T ultrassensível foram dosados e nenhum marcador de elevou após a isquemia cardíaca seguida de reperfusão. A troponina I cardíaca nitrada foi caracterizada por espectrometria de massas. Esse proteína é um potencial marcador circulante sensível para o diagnóstico e prognóstico precoce de isquemia cardíaca com ou sem necrose do miocárdio / Worldwide, millions of patients are treated in emergencies because they had acute-onset chest pain, but only a portion is due to coronary syndrome. In situations like this is extremely important to distinguish when the chest pain is due to myocardial ischemia, as this is high risk and initiation of treatment should be immediate. New biomarkers are needed to assist clinical decision-making in ACS. Recently, the quantification of ultra-sensitive tests for troponins has been widely used for diagnosis and prognosis of myocardial ischemia, however the reference values was not well validated and established for different subjects groups. The present study identified the nitrated cardiac troponin I as a novel biomarker of cardiac ischemia. We performed immunofluorescence colocalization marking of cardiac troponin I and nitrotyrosine in cell and rat model of cardiac ischemia, suggesting that cardiac troponin I is a nitrated protein. From serum of porcine models cardiac ischemia was made enrichment of nitrated proteins by immunoprecipitation with anti-nitrotyrosine followed by detection of cardiac troponin I by western blot. It was possible to identify the cardiac troponin I in serum nitrated few minutes after the ischemic event, which remains current for up to 24 hours. In these samples, other markers of cardiac ischemia such as CK-MB, troponin I and ultra-sensitive troponin T did not increase after ischemia followed by reperfusion. Nitrated cardiac troponin I was characterized by MS/MS. The xii nitrated cardiac troponin I is a potential circulating marker sensitive for the diagnosis and prognosis for early cardiac ischemia with or without myocardial necrosis

No description available.

Foraging behaviour in Drosophila melanogaster larvae is influenced by natural allelic variation in the foraging (for) gene that encodes a cyclic GMP – dependent protein Kinase (PKG), such that rovers (forR) traverse greater distances while foraging than sitters (fors). Foraging behaviour is also influenced by natural allelic variation in the wings up A (wupA) gene that encodes the Troponin-I protein (TnI). Specifically, wupAlow allele suppresses the dominance of the forR allele, turning rovers into sitters. The dominance of the natural wupA alleles and their interactions with allelic combinations in for has not been characterized. I conducted various crosses and found that wupA alleles exhibit incomplete dominance. More importantly, I found that allelic combinations of wupA and for gave rise to a range in larval foraging behaviour. In this study, I propose that this gradient effect in foraging behaviour is due to variation in levels of PKG activity and TnI phosphorylation potential.

Foraging behaviour in Drosophila melanogaster larvae is influenced by natural allelic variation in the foraging (for) gene that encodes a cyclic GMP – dependent protein Kinase (PKG), such that rovers (forR) traverse greater distances while foraging than sitters (fors). Foraging behaviour is also influenced by natural allelic variation in the wings up A (wupA) gene that encodes the Troponin-I protein (TnI). Specifically, wupAlow allele suppresses the dominance of the forR allele, turning rovers into sitters. The dominance of the natural wupA alleles and their interactions with allelic combinations in for has not been characterized. I conducted various crosses and found that wupA alleles exhibit incomplete dominance. More importantly, I found that allelic combinations of wupA and for gave rise to a range in larval foraging behaviour. In this study, I propose that this gradient effect in foraging behaviour is due to variation in levels of PKG activity and TnI phosphorylation potential.

I investigated SL trans-splicing in the troponin I gene of Ciona intestinalis. Experimental mutation of the AG dinucleotide adjacent to the natural trans-splice acceptor site (-64) in CiTnI/nuclacZ constructs eliminated trans-splicing to that site in Ciona embryos but activated trans-splicing at cryptic acceptor sites at -76 and -39, adjacent to the nearest AG dinucleotides. However, not all AG dinucleotides specify cryptic acceptor sites because outron internal deletions or 3'truncation mutants were trans-spliced at a far-upstream AG-adjacent cryptic site (-346), leaving many AGs in the retained outron segments. Thus, additional sequence elements that are present only in the -346 and -76/-64/-39 regions are required for cryptic acceptor activity. All mutant constructs generated detectable beta-gal enzyme expression, although the mutant with the longest retained-outron segment appeared less active. Therefore, mRNA accumulation and translation do not require trans-splicing to the natural acceptor site, although they may be facilitated by the normal removal of the outron during trans-splicing.

A insuficiência cardíaca é a doença crônica com maior impacto na sobrevida e qualidade de vida dos pacientes. Apesar do constante desenvolvimento de novas estratégias de tratamento, esta doença continua atingindo altos índices de mortalidade. O coração adulto tem capacidade de regeneração limitada e há grande evidência experimental de que os transplantes de células-tronco poderiam ser uma abordagem eficiente na recuperação do miocárdio lesado. Contudo, a maioria dos estudos são realizados em cardiomiopatias isquêmicas, existindo poucos estudos na cardiomiopatia dilatada (CMD). Em função disto, este trabalho foi realizado com o objetivo de avaliar a regeneração do miocárdio em coelhos com CMD induzida pela doxorrubicina, por meio do uso de células-tronco mesenquimais (MSC) obtidas de tecido adiposo, associadas ou não com plasma rico em plaquetas (PRP). Foram utilizadas 40 coelhas, Nova Zelândia, e um coelho macho doador das MSCs derivadas do tecido adiposo. As coelhas foram divididas em dois grupos: CMD induzida pela doxorrubicina e o grupo saudável. Cada grupo foi subdividido conforme o tratamento recebido: solução fisiológica, MCSs, PRP e MSCs associadas ao PRP. Os subgrupos receberam o tratamento por injeção diretamente no miocárdio no ventrículo esquerdo mediante toracoscopia vídeo assistida. Os coelhos foram avaliados por exames de ecocardiograma, eletrocardiograma, troponina I, no dia da chegada, após a indução da CMD e 15 dias após o recebimento das terapias. Nesta última avaliação, foi realizada a eutanásia e coletado o coração para análise histológica. Foi observado que após a indução, a troponina I se elevou, o segmento QRS visto no eletrocardiograma, aumentou e, no ecocardiograma, as frações de ejeção (FE) e encurtamento (FS) diminuíram e o diâmetro sistólico do ventrículo esquerdo (VEs) aumentou, em todos os animais avaliados. Após os tratamentos, o subgrupo MSCs obtiveram os melhores resultados em todas as análises citadas. Houve menor elevação da troponina I, o segmento QRS diminuiu, as FS e FE aumentaram e o VEs diminuiu. No exame histopatógico, analisado pela coloração de hematoxicilina-eosina, constatou-se que o subgrupo MSCs apresentou menos lesões, e nos subgrupos MSCs associadas com PRP, solução fisiológica e PRP as lesões aumentaram gradualmente, respectivamente. Os resultados sugerem que o uso das MSCs melhoraram a função cardíaca em coelhos com cardiomiopatia dilatada e que há necessidade de mais estudos no uso de PRP no miocárdio. / Heart failure is a chronic disease with major impact on survival and quality of patient’s life. Despite the constant development of new treatment strategies, this disease still affects high mortality rates. The adult heart has limited ability to regenerate and there is experimental evidence that large transplants of stem cells could be an effective approach in the recovery of injured myocardium. However, most studies are performed in ischemic cardiomyopathy, there are few studies in dilated cardiomyopathy. Because of this, this study aimed at evaluating the regeneration of the myocardium in rabbits with dilated cardiomyopathy induced by doxorubicin through the use of mesenchymal stem cell (MSC) derived from adipose tissue, associated or not with platelet-rich plasma (PRP). 40 New Zealand rabbits were utilized and a male rabbit donor MSCs derived from adipose tissue. The rabbits were divided into two groups: dilated cardiomyopathy doxorubicin-induced and the healthy group. Each group was divided according to treatment received: saline, MSCs, PRP and MSCs associated with PRP. The subgroups receiving treatment through an injection directly into the myocardium of the left ventricle through video-assisted thoracoscopy. The rabbits were evaluated by echocardiogram, electrocardiogram, troponin I, on the day of arrival, after induction of dilated cardiomyopathy and 15 days after receipt of therapies. This last evaluation, euthanasia was performed and the hearts collected for histological analysis. It was observed that after induction the troponin I increased, the QRS segment, seen on the electrocardiogram, increased, and, in echocardiography, the ejection and shortening fractions decreased, and left ventricular systolic diameter increased in all animals evaluated. After treatments, the subgroup MSCs have the best results in all tests cited. There was a lower elevation of troponin I, decreased QRS segment, the ejection and shortening fractions increased and left ventricular systolic diameter decreased. On examination histologic, analyzed by hematoxylin-eosin staining, the subgroup found that MSCs had fewer injuries, and in the subgroups MSCs associated with PRP, PRP and saline lesions gradually increased, respectively. The results suggest that the use of MSCs improved cardiac function in rabbits with dilated cardiomyopathy and that there is need for more studies on the use of PRP in the myocardium.

Em todo o mundo, milhões de pacientes são atendidos em emergências por apresentarem dor torácica de início aguda, mas apenas uma parcela deve-se a síndrome coronariana aguda (SCA). Em situações como essa é de extrema importância distinguir quando a dor torácica é devido à isquemia do miocárdio, pois esta é de alto risco e o início do tratamento deve ser imediato. Novos biomarcadores são necessários para auxiliar no diagnóstico e conduta clínica a ser tomada diante de situações de emergência como esta. Recentemente a quantificação de troponinas através de ensaios ultrassensíveis tem sido amplamente utilizado para diagnósticos e prognóstico de isquemia cardíaca, porém esses ensaios não tiveram seus valores de referências estabelecidos e validados para diversas situações clínicas. O presente estudo identificou a troponina I cardíaca nitrada como um novo biomarcador para isquemia cardíaca. Através de experimentos de imunoluorecência, foi possível colocalizar a marcação de troponina I cardíaca e nitrotirosina em modelos celulares e murinos de isquemia cardíaca, sugerindo assim que a troponina I cardíaca é nitrada. A partir do soro de modelos porcinos de isquemia, foi realizado o enriquecimento de proteínas nitradas por imunoprecipitação seguido da identificação da troponina I cardíaca por western blot. Dessa maneira foi possível identificar a troponina I cardíaca nitrada no soro poucos minutos após o evento x isquêmico, a qual permaneceu circulante por até 24 horas. Nessas mesmas amostras outros biomarcadores de isquemia como CKMB, Troponina I e Troponina T ultrassensível foram dosados e nenhum marcador de elevou após a isquemia cardíaca seguida de reperfusão. A troponina I cardíaca nitrada foi caracterizada por espectrometria de massas. Esse proteína é um potencial marcador circulante sensível para o diagnóstico e prognóstico precoce de isquemia cardíaca com ou sem necrose do miocárdio / Worldwide, millions of patients are treated in emergencies because they had acute-onset chest pain, but only a portion is due to coronary syndrome. In situations like this is extremely important to distinguish when the chest pain is due to myocardial ischemia, as this is high risk and initiation of treatment should be immediate. New biomarkers are needed to assist clinical decision-making in ACS. Recently, the quantification of ultra-sensitive tests for troponins has been widely used for diagnosis and prognosis of myocardial ischemia, however the reference values was not well validated and established for different subjects groups. The present study identified the nitrated cardiac troponin I as a novel biomarker of cardiac ischemia. We performed immunofluorescence colocalization marking of cardiac troponin I and nitrotyrosine in cell and rat model of cardiac ischemia, suggesting that cardiac troponin I is a nitrated protein. From serum of porcine models cardiac ischemia was made enrichment of nitrated proteins by immunoprecipitation with anti-nitrotyrosine followed by detection of cardiac troponin I by western blot. It was possible to identify the cardiac troponin I in serum nitrated few minutes after the ischemic event, which remains current for up to 24 hours. In these samples, other markers of cardiac ischemia such as CK-MB, troponin I and ultra-sensitive troponin T did not increase after ischemia followed by reperfusion. Nitrated cardiac troponin I was characterized by MS/MS. The xii nitrated cardiac troponin I is a potential circulating marker sensitive for the diagnosis and prognosis for early cardiac ischemia with or without myocardial necrosis