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1.
Clin Infect Dis ; 65(7): 1103-1111, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-28575239

RESUMO

Background: Chagas disease, caused by the protozoan Trypanosoma cruzi, is endemic in Latin America and affects 10 million people worldwide. Approximately 12000 deaths attributable to Chagas disease occur annually due to chronic Chagas disease cardiomyopathy (CCC), an inflammatory cardiomyopathy presenting with heart failure and arrythmia; 30% of infected subjects develop CCC years after infection. Genetic mechanisms play a role in differential progression to CCC, but little is known about the role of epigenetic modifications in pathological gene expression patterns in CCC patients' myocardium. DNA methylation is the most common modification in the mammalian genome. Methods: We investigated the impact of genome-wide cardiac DNA methylation on global gene expression in myocardial samples from end-stage CCC patients, compared to control samples from organ donors. Results: In total, 4720 genes were differentially methylated between CCC patients and controls, of which 399 were also differentially expressed. Several of them were related to heart function or to the immune response and had methylation sites in their promoter region. Reporter gene and in silico transcription factor binding analyses indicated promoter methylation modified expression of key genes. Among those, we found potassium channel genes KCNA4 and KCNIP4, involved in electrical conduction and arrythmia, SMOC2, involved in matrix remodeling, as well as enkephalin and RUNX3, potentially involved in the increased T-helper 1 cytokine-mediated inflammatory damage in heart. Conclusions: Results support that DNA methylation plays a role in the regulation of expression of pathogenically relevant genes in CCC myocardium, and identify novel potential disease pathways and therapeutic targets in CCC.

2.
J Infect Dis ; 214(1): 161-5, 2016 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-26951817

RESUMO

Long noncoding RNAs (lncRNAs) modulate gene expression at the epigenetic, transcriptional, and posttranscriptional levels. Dysregulation of the lncRNA known as myocardial infarction-associated transcript (MIAT) has been associated with myocardial infarction. Chagas disease causes a severe inflammatory dilated chronic cardiomyopathy (CCC). We investigated the role of MIAT in CCC. A whole-transcriptome analysis of heart biopsy specimens and formalin-fixed, paraffin-embedded samples revealed that MIAT was overexpressed in patients with CCC, compared with subjects with noninflammatory dilated cardiomyopathy and controls. These results were confirmed in a mouse model. Results suggest that MIAT is a specific biomarker of CCC.


Assuntos
Doença de Chagas/complicações , Doença de Chagas/genética , Perfilação da Expressão Gênica , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/genética , RNA Longo não Codificante , Animais , Doença de Chagas/fisiopatologia , Feminino , Humanos , Masculino , Camundongos , Fatores de Transcrição
3.
Rev. Soc. Cardiol. Estado de Säo Paulo ; 24(3): 54-61, jul.-set.2014.
Artigo em Português | LILACS | ID: lil-763798

RESUMO

O transplante cardíaco é reconhecido como o melhor tratamentopara a insuficiência cardíaca refratária. O Brasil tem um grandepotencial de aumento do número de transplantes, já que atualmenteo aproveitamento dos potenciais doadores é muito baixo. Os pioresresultados do transplante aqui, quando comparados aos dadosinternacionais, decorrem, em parte, da associação de doadorespior cuidados e receptores mais graves, com limitação de acessoaos dispositivos de assistência circulatória. O desenvolvimento decentros transplantadores capazes de melhorar a condição clínicados receptores e de criar condições para aumentar a efetivaçãodos doadores pode ter um impacto positivo no número e nosresultados dos transplantes. A organização do Heart Team, umaequipe multidisciplinar envolvendo profissionais com funçõescomplementares, é essencial para o aprimoramento não só do cuidadoao receptor, mas também de todo o processo envolvido no transplantecardíaco, incluindo a captação de órgãos. A equipe deve ser compostapor cardiologistas clínicos e cirurgiões cardiovasculares dedicadosao transplante cardíaco, outros especialistas (como intensivistas,infectologistas e patologistas) fundamentais no cuidado do receptor,enfermeiros e biomédicos envolvidos na avaliação e cuidado dosdoadores e na captação do órgão, enfermeiros dedicados à assistênciados receptores e uma equipe multidisciplinar envolvida em todo oprocesso, desde a avaliação do paciente com insuficiência cardíacarefratária, potencial candidato ao transplante, até o seguimento esuporte do transplantado cardíaco e seus familiares. Esta abordagemcompleta e harmoniosa que o Heart Team possibilita é certamente ocaminho para o crescimento do transplante cardíaco no Brasil.


Heart transplant is recognized as the treatment of choice forrefractory heart failure. Brazil has a great potential to increase thenumber of heart transplants, as the use of potential donors is nowtoo low. The worst results of heart transplants in Brazil, comparedwith international data, may be, in part, due to the association ofpoor care of donors and poor conditions of recipients, with limitedaccess to circulatory assistance devices. The development of hearttransplant centers capable of improving the clinical conditions ofthe recipients and creating ways to increase the use of donors mayhave a positive impact in the number and results of transplants. Theorganization of a “Heart Team”, a multidisciplinary team evolvingprofessionals with complementary functions, is essential not only toimprove the care of recipients, but also to improve the whole processof heart transplant, including organ harvesting. The team must becomposed of cardiologists and cardiovascular surgeons dedicated toheart transplant, other specialists (such as intensivists, infectologistsand pathologists) who have a crucial role in the care of recipients;nurses and biomedicals evolved in the evaluation and care of donorsand in organ harvesting; nurses dedicated in recipients assistanceand a multidisciplinary team evolved in the whole process, sincethe evaluation of the patient with refractory heart failure, a potentialcandidate for heart transplant, up to the follow-up and support ofheart transplanted patients and their families. This complete andharmonious approach that “Heart Team” enables is certainly theway to improve heart transplant in Brazil.


Assuntos
Humanos , Insuficiência Cardíaca/cirurgia , Insuficiência Cardíaca/diagnóstico , Transplante de Coração/reabilitação , Coleta de Tecidos e Órgãos/métodos , Equipe de Assistência ao Paciente/ética , Seleção do Doador/métodos
4.
Mediators Inflamm ; 2014: 914326, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25152568

RESUMO

BACKGROUND: Chronic Chagas disease cardiomyopathy (CCC), a late consequence of Trypanosoma cruzi infection, is an inflammatory cardiomyopathy with prognosis worse than those of noninflammatory etiology (NIC). Although the T cell-rich myocarditis is known to play a pathogenetic role, the relative contribution of each of the functional T cell subsets has never been thoroughly investigated. We therefore assessed gene expression of cytokines and transcription factors involved in differentiation and effector function of each functional T cell subset (TH1/TH2/TH17/Treg) in CCC, NIC, and heart donor myocardial samples. METHODS AND RESULTS: Quantitative PCR showed markedly upregulated expression of IFN-γ and transcription factor T-bet, and minor increases of GATA-3; FoxP3 and CTLA-4; IL-17 and IL-18 in CCC as compared with NIC samples. Conversely, cytokines expressed by TH2 cells (IL-4, IL-5, and IL-13) or associated with Treg (TGF-ß and IL-10) were not upregulated in CCC myocardium. Expression of TH1-related genes such as T-bet, IFN-γ, and IL-18 correlated with ventricular dilation, FoxP3, and CTLA-4. CONCLUSIONS: Results are consistent with a strong local TH1-mediated response in most samples, possibly associated with pathological myocardial remodeling, and a proportionally smaller FoxP3(+)CTLA4(+) Treg cell population, which is unable to completely curb IFN-γ production in CCC myocardium, therefore fueling inflammation.


Assuntos
Cardiomiopatia Chagásica/imunologia , Cardiomiopatia Chagásica/metabolismo , Miocárdio/metabolismo , Adulto , Feminino , Fatores de Transcrição Forkhead/metabolismo , Fator de Transcrição GATA3/metabolismo , Humanos , Masculino , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Proteínas com Domínio T/metabolismo , Células Th1/metabolismo
5.
Int J Cardiol ; 175(3): 409-17, 2014 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-24910366

RESUMO

BACKGROUND/METHODS: Chagas disease is caused by an intracellular parasite, Trypanosoma cruzi, and it is a leading cause of heart failure in Latin America. The main clinical consequence of the infection is the development of a Chronic Chagas disease Cardiomyopathy (CCC), which is characterized by myocarditis, hypertrophy and fibrosis and affects about 30% of infected patients. CCC has a worse prognosis than other cardiomyopathies, like idiopathic dilated cardiomyopathy (DCM). It is well established that myocardial gene expression patterns are altered in CCC, but the molecular mechanisms underlying these differences are not clear. MicroRNAs are recently discovered regulators of gene expression, and are recognized as important factors in heart development and cardiovascular disorders (CD). We analyzed the expression of nine different miRNAs in myocardial tissue samples of CCC patients in comparison to DCM patients and samples from heart transplant donors. Using the results of a cDNA microarray database on CCC and DCM myocardium, signaling networks were built and nodal molecules were identified. RESULTS: We observed that five miRNAs were significantly altered in CCC and three in DCM; importantly, three miRNAs were significantly reduced in CCC as compared to DCM. We observed that multiple gene targets of the differentially expressed miRNAs showed a concordant inverse expression in CCC. Significantly, most gene targets and involved networks belong to crucial disease-related signaling pathways. CONCLUSION: These results suggest that miRNAs may play a major role in the regulation of gene expression in CCC pathogenesis, with potential implication as diagnostic and prognostic tools.


Assuntos
Cardiomiopatia Chagásica/metabolismo , MicroRNAs/biossíntese , Adolescente , Adulto , Biomarcadores/metabolismo , Cardiomiopatia Chagásica/diagnóstico , Cardiomiopatia Chagásica/genética , Doença Crônica , Feminino , Redes Reguladoras de Genes/fisiologia , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Miocárdio/metabolismo , Miocárdio/patologia , Adulto Jovem
6.
Arq. bras. cardiol ; 102(5): 505-509, 10/06/2014. tab, graf
Artigo em Português | LILACS | ID: lil-711087

RESUMO

Fundamento: Discordâncias entre diagnóstico pre e post-mortem são relatadas na literatura, podendo variar de 4,1 a 49,8% dentre os casos encaminhados para exame necroscópico, com importante repercussão no tratamento dos pacientes. Objetivo: Analisar pacientes com óbito após o transplante cardíaco e confrontar os diagnósticos pre e post-mortem. Métodos: Por meio da revisão de prontuários, foram analisados dados clínicos, presença de comorbidades, esquema de imunossupressão, exames laboratoriais, causa clínica do óbito e causa do óbito à necrópsia. Foram confrontadas, então, a causa clínica e a causa necroscópica do óbito de cada paciente. Resultados: Foram analisados 48 óbitos submetidos à necrópsia no período de 2000 a 2010; 29 (60,4%) tiveram diagnósticos clínico e necroscópico concordantes, 16 (33,3%) tiveram diagnósticos discordantes e três (6,3%) tiveram diagnóstico não esclarecido. Entre os discordantes, 15 (31,3%) apresentaram possível impacto na sobrevida e um (2,1%) não apresentou impacto na sobrevida. O principal diagnóstico clínico feito equivocadamente foi o de infecção, com cinco casos (26,7% dos discordantes), seguido por rejeição hiperaguda, com quatro casos (20% dos discordantes), e tromboembolismo pulmonar, com três casos (13,3% dos discordantes). Conclusão: Discordâncias entre o diagnóstico clínico e achados da necrópsia são comumente encontradas no transplante cardíaco. Novas estratégias no aperfeiçoamento do diagnóstico clínico devem ser introduzidas, considerando-se os resultados da necrópsia para melhoria do tratamento da insuficiência cardíaca por meio do transplante cardíaco. .


Background: Discrepancies between pre and post-mortem diagnoses are reported in the literature, ranging from 4.1 to 49.8 % in cases referred for necropsy, with important impact on patient treatment. Objective: To analyze patients who died after cardiac transplantation and to compare the pre- and post-mortem diagnoses. Methods: Perform a review of medical records and analyze clinical data, comorbidities, immunosuppression regimen, laboratory tests, clinical cause of death and cause of death at the necropsy. Then, the clinical and necroscopic causes of death of each patient were compared. Results: 48 deaths undergoing necropsy were analyzed during 2000-2010; 29 (60.4 %) had concordant clinical and necroscopic diagnoses, 16 (33.3%) had discordant diagnoses and three (6.3%) had unclear diagnoses. Among the discordant ones, 15 (31.3%) had possible impact on survival and one (2.1%) had no impact on survival. The main clinical misdiagnosis was infection, with five cases (26.7 % of discordant), followed by hyperacute rejection, with four cases (20 % of the discordant ones), and pulmonary thromboembolism, with three cases (13.3% of discordant ones). Conclusion: Discrepancies between clinical diagnosis and necroscopic findings are commonly found in cardiac transplantation. New strategies to improve clinical diagnosis should be made, considering the results of the necropsy, to improve the treatment of heart failure by heart transplantation. .


Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Autopsia , Causas de Morte , Transplante de Coração/mortalidade , Erros de Diagnóstico/estatística & dados numéricos , Registros Médicos/estatística & dados numéricos , Estudos Retrospectivos , Sobrevida , Fatores de Tempo
7.
Arq Bras Cardiol ; 102(5): 505-9, 2014 May.
Artigo em Inglês, Português | MEDLINE | ID: mdl-24759949

RESUMO

BACKGROUND: Discrepancies between pre and post-mortem diagnoses are reported in the literature, ranging from 4.1 to 49.8 % in cases referred for necropsy, with important impact on patient treatment. OBJECTIVE: To analyze patients who died after cardiac transplantation and to compare the pre- and post-mortem diagnoses. METHODS: Perform a review of medical records and analyze clinical data, comorbidities, immunosuppression regimen, laboratory tests, clinical cause of death and cause of death at the necropsy. Then, the clinical and necroscopic causes of death of each patient were compared. RESULTS: 48 deaths undergoing necropsy were analyzed during 2000-2010; 29 (60.4 %) had concordant clinical and necroscopic diagnoses, 16 (33.3%) had discordant diagnoses and three (6.3%) had unclear diagnoses. Among the discordant ones, 15 (31.3%) had possible impact on survival and one (2.1%) had no impact on survival. The main clinical misdiagnosis was infection, with five cases (26.7 % of discordant), followed by hyperacute rejection, with four cases (20 % of the discordant ones), and pulmonary thromboembolism, with three cases (13.3% of discordant ones). CONCLUSION: Discrepancies between clinical diagnosis and necroscopic findings are commonly found in cardiac transplantation. New strategies to improve clinical diagnosis should be made, considering the results of the necropsy, to improve the treatment of heart failure by heart transplantation.


Assuntos
Autopsia , Causas de Morte , Transplante de Coração/mortalidade , Adulto , Erros de Diagnóstico/estatística & dados numéricos , Feminino , Humanos , Masculino , Registros Médicos/estatística & dados numéricos , Pessoa de Meia-Idade , Estudos Retrospectivos , Sobrevida , Fatores de Tempo
8.
PLoS One ; 8(12): e83446, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24367596

RESUMO

AIMS: Chagas disease, caused by the protozoan Trypanosoma cruzi is endemic in Latin America, and may lead to a life-threatening inflammatory dilated, chronic Chagas cardiomyopathy (CCC). One third of T. cruzi-infected individuals progress to CCC while the others remain asymptomatic (ASY). A possible genetic component to disease progression was suggested by familial aggregation of cases and the association of markers of innate and adaptive immunity genes with CCC development. Since mutations in multiple sarcomeric genes, including alpha-cardiac actin (ACTC1) have been involved in hereditary dilated cardiomyopathy, we investigated the involvement of the ACTC1 gene in CCC pathogenesis. METHODS AND RESULTS: We conducted a proteomic and genetic study on a Brazilian study population. The genetic study was done on a main cohort including 118 seropositive asymptomatic subjects and 315 cases and the replication was done on 36 asymptomatic and 102 CCC cases. ACTC1 protein and mRNA levels were lower in myocardial tissue from patients with end-stage CCC than those found in hearts from organ donors. Genotyping a case-control cohort of CCC and ASY subjects for all informative single nucleotide polymorphism (SNP) in the ACTC1 gene identified rs640249 SNP, located at the 5' region, as associated to CCC. Associations are borderline after correction for multiple testing. Correlation and haplotype analysis led to the identification of a susceptibility haplotype. Functional assays have shown that the rs640249A/C polymorphism affects the binding of transcriptional factors in the promoter regions of the ACTC1 gene. Confirmation of the detected association on a larger independent replication cohort will be useful. CONCLUSIONS: Genetic variations at the ACTC1 gene may contribute to progression to chronic Chagas Cardiomyopathy among T. cruzi-infected patients, possibly by modulating transcription factor binding to ACTC1 promoter regions.


Assuntos
Actinas/genética , Cardiomiopatia Chagásica/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único , Actinas/metabolismo , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Miocárdio/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
9.
PLOS ONE ; 8(12): 1-16, 2013. ilus
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: ses-29744

RESUMO

Aims: Chagas disease, caused by the protozoan Trypanosoma cruzi is endemic in Latin America, and may lead to alife-threatening inflammatory dilated, chronic Chagas cardiomyopathy (CCC). One third of T. cruzi-infectedindividuals progress to CCC while the others remain asymptomatic (ASY). A possible genetic component to diseaseprogression was suggested by familial aggregation of cases and the association of markers of innate and adaptiveimmunity genes with CCC development. Since mutations in multiple sarcomeric genes, including alpha-cardiac actin(ACTC1) have been involved in hereditary dilated cardiomyopathy, we investigated the involvement of the ACTC1gene in CCC pathogenesis.Methods and Results: We conducted a proteomic and genetic study on a Brazilian study population. The geneticstudy was done on a main cohort including 118 seropositive asymptomatic subjects and 315 cases and thereplication was done on 36 asymptomatic and 102 CCC cases. ACTC1 protein and mRNA levels were lower inmyocardial tissue from patients with end-stage CCC than those found in hearts from organ donors. Genotyping acase-control cohort of CCC and ASY subjects for all informative single nucleotide polymorphism (SNP) in the ACTC1gene identified rs640249 SNP, located at the 5’ region, as associated to CCC. Associations are borderline aftercorrection for multiple testing. Correlation and haplotype analysis led to the identification of a susceptibility haplotype.Functional assays have shown that the rs640249A/C polymorphism affects the binding of transcriptional factors in thepromoter regions of the ACTC1 gene. Confirmation of the detected association on a larger independent replicationcohort will be useful.Conclusions: Genetic variations at the ACTC1 gene may contribute to progression to chronic ChagasCardiomyopathy among T. cruzi-infected patients, possibly by modulating transcription factor binding to ACTC1promoter regions. (AU)


Assuntos
Doença de Chagas , Variação Genética , Cardiomiopatia Chagásica
10.
PLoS Negl Trop Dis ; 6(10): e1867, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23150742

RESUMO

BACKGROUND: Chronic Chagas cardiomyopathy (CCC), a life-threatening inflammatory dilated cardiomyopathy, affects 30% of the approximately 8 million patients infected by Trypanosoma cruzi. Even though the Th1 T cell-rich myocarditis plays a pivotal role in CCC pathogenesis, little is known about the factors controlling inflammatory cell migration to CCC myocardium. METHODS AND RESULTS: Using confocal immunofluorescence and quantitative PCR, we studied cell surface staining and gene expression of the CXCR3, CCR4, CCR5, CCR7, CCR8 receptors and their chemokine ligands in myocardial samples from end-stage CCC patients. CCR5+, CXCR3+, CCR4+, CCL5+ and CXCL9+ mononuclear cells were observed in CCC myocardium. mRNA expression of the chemokines CCL5, CXCL9, CXCL10, CCL17, CCL19 and their receptors was upregulated in CCC myocardium. CXCL9 mRNA expression directly correlated with the intensity of myocarditis, as well as with mRNA expression of CXCR3, CCR4, CCR5, CCR7, CCR8 and their ligands. We also analyzed single-nucleotide polymorphisms for genes encoding the most highly expressed chemokines and receptors in a cohort of Chagas disease patients. CCC patients with ventricular dysfunction displayed reduced genotypic frequencies of CXCL9 rs10336 CC, CXCL10 rs3921 GG, and increased CCR5 rs1799988CC as compared to those without dysfunction. Significantly, myocardial samples from CCC patients carrying the CXCL9/CXCL10 genotypes associated to a lower risk displayed a 2-6 fold reduction in mRNA expression of CXCL9, CXCL10, and other chemokines and receptors, along with reduced intensity of myocarditis, as compared to those with other CXCL9/CXCL10 genotypes. CONCLUSIONS: Results may indicate that genotypes associated to reduced risk in closely linked CXCL9 and CXCL10 genes may modulate local expression of the chemokines themselves, and simultaneously affect myocardial expression of other key chemokines as well as intensity of myocarditis. Taken together our results may suggest that CXCL9 and CXCL10 are master regulators of myocardial inflammatory cell migration, perhaps affecting clinical progression to the life-threatening form of CCC.


Assuntos
Cardiomiopatia Chagásica/genética , Cardiomiopatia Chagásica/patologia , Quimiocina CXCL10/biossíntese , Quimiocina CXCL9/biossíntese , Polimorfismo Genético , Trypanosoma cruzi/patogenicidade , Adolescente , Adulto , Quimiocina CXCL10/genética , Quimiocina CXCL9/genética , Resistência à Doença , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
11.
PLoS Negl Trop Dis ; 5(6): e1205, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21738806

RESUMO

BACKGROUND: Chronic Chagas disease cardiomyopathy (CCC) is an inflammatory dilated cardiomyopathy with a worse prognosis than other cardiomyopathies. CCC occurs in 30 % of individuals infected with Trypanosoma cruzi, endemic in Latin America. Heart failure is associated with impaired energy metabolism, which may be correlated to contractile dysfunction. We thus analyzed the myocardial gene and protein expression, as well as activity, of key mitochondrial enzymes related to ATP production, in myocardial samples of end-stage CCC, idiopathic dilated (IDC) and ischemic (IC) cardiomyopathies. METHODOLOGY/PRINCIPAL FINDINGS: Myocardium homogenates from CCC (N=5), IC (N=5) and IDC (N=5) patients, as well as from heart donors (N=5) were analyzed for protein and mRNA expression of mitochondrial creatine kinase (CKMit) and muscular creatine kinase (CKM) and ATP synthase subunits aplha and beta by immunoblotting and by real-time RT-PCR. Total myocardial CK activity was also assessed. Protein levels of CKM and CK activity were reduced in all three cardiomyopathy groups. However, total CK activity, as well as ATP synthase alpha chain protein levels, were significantly lower in CCC samples than IC and IDC samples. CCC myocardium displayed selective reduction of protein levels and activity of enzymes crucial for maintaining cytoplasmic ATP levels. CONCLUSIONS/SIGNIFICANCE: The selective impairment of the CK system may be associated to the loss of inotropic reserve observed in CCC. Reduction of ATP synthase alpha levels is consistent with a decrease in myocardial ATP generation through oxidative phosphorylation. Together, these results suggest that the energetic deficit is more intense in the myocardium of CCC patients than in the other tested dilated cardiomyopathies.


Assuntos
Complexos de ATP Sintetase/metabolismo , Cardiomiopatia Chagásica/fisiopatologia , Creatina Quinase Mitocondrial/metabolismo , Miocárdio/enzimologia , Complexos de ATP Sintetase/genética , Adolescente , Adulto , Creatina Quinase Mitocondrial/genética , Perfilação da Expressão Gênica , Humanos , Immunoblotting , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto Jovem
12.
Rev. bras. cir. cardiovasc ; 24(4): 453-462, out.-dez. 2009. tab
Artigo em Inglês, Português | LILACS | ID: lil-540746

RESUMO

Objetivos: Com o aumento da expectativa de vida nas últimas décadas, tem-se um aumento concomitante da prevalência da estenose aórtica degenerativa e da doença aterosclerótica arterial coronária. O presente estudo visa avaliar a influência da doença aterosclerótica arterial coronária crítica em pacientes portadores de estenose aórtica submetidos ao implante isolado de prótese valvar ou combinado à revascularização do miocárdio. Métodos: No período de janeiro de 2001 a março de 2006, foram analisados 448 pacientes submetidos ao implante isolado de prótese valvar aórtica (Grupo I) e 167 pacientes submetidos à substituição valvar aórtica combinada à revascularização do miocárdio (Grupo II). As variáveis pré e intra-operatórias eleitas para análise foram: sexo, idade, índice de massa corpórea, acidente vascular cerebral, diabete melito, doença pulmonar obstrutiva crônica, febre reumática, hipertensão arterial sistêmica, endocardite, infarto agudo do miocárdio e tabagismo, fração de ejeção do ventrículo esquerdo, doença aterosclerótica arterial coronária crítica, fibrilação atrial crônica, operação valvar aórtica prévia (conservadora), classe funcional de insuficiência cardíaca congestiva, valor sérico de creatinina, colesterol total, tamanho da prótese utilizada, extensão e número de anastomoses distais da revascularização do miocárdio realizada, tempos de circulação extracorpórea de pinçamento aórtico. No estudo estatístico empregou-se análise univariada multivariada. Resultados: A mortalidade hospitalar foi 14,3 por cento (64 óbitos) no Grupo I, sendo 14,5 por cento (58 óbitos) nos pacientes sem doença aterosclerótica arterial coronária crítica associada (Grupo IB) e 12,8 por cento (6 óbitos) nos que apresentavam essa associação (Grupo IA). A mortalidade hospitalar no Grupo II foi 17,6 por cento (29 óbitos), sendo 16,1 por cento (20 óbitos) nos pacientes submetidos à substituição valvar aórtica combinada à revascularização completa do miocárdio...


Objectives: With the increase in life expectancy occurred in recent decades, it has been noted the concomitant increase in the prevalence of aortic stenosis and degenerative disease of atherosclerotic coronary artery. This study aims to evaluate the influence of atherosclerotic coronary artery disease in patients with critical aortic stenosis undergoing isolated or combined implant valve prosthesis and coronary artery by pass grafting. Methods: In the period of January 2001 to March 2006, there were analyzed 448 patients undergoing isolated implant aortic valve prosthesis (Group I) and 167 patients undergoing aortic valve prosthesis implant combined with coronary artery bypass grafting (Group II). Pre- and intra-operative variables elected for analysis were: age, gender, body mass index, stroke, diabetes mellitus, chronic obstructive pulmonary disease, rheumatic fever, hypertension, endocarditis, acute myocardial infarction, smoking, Fraction of the left ventricular ejection, critical atherosclerotic coronary artery disease, chronic atrial fibrillation, aortic valve operation prior (conservative), functional class of congestive heart failure, value serum creatinine, total cholesterol, size of the prosthesis used, length and number of distal anastomoses held in myocardial revascularization, duration of cardiopulmonary bypass and aortic clamping time. The statistical study employed invariant and multivariate analysis. Results: Hospital mortality was 14.3 percent (64 deaths) in Group I, and 14.5 percent (58 deaths) in patients with atherosclerotic coronary artery disease associated criticism (Group IB) and 12.8 percent (six deaths) in which had this association (Group IA). Hospital mortality in Group II was 17.6 percent (29 deaths), and 16.1 percent (20 deaths) in patients undergoing implantation of prosthetic aortic valve combined to complete myocardial revascularization (Group II) and 20.9 percent (nine deaths) in the myocardial revascularization...


Assuntos
Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estenose da Valva Aórtica/cirurgia , Ponte de Artéria Coronária , Doença da Artéria Coronariana/cirurgia , Implante de Prótese de Valva Cardíaca , Mortalidade Hospitalar , Complicações Pós-Operatórias/mortalidade , Estenose da Valva Aórtica/mortalidade , Terapia Combinada , Doença da Artéria Coronariana/mortalidade , Métodos Epidemiológicos , Complicações Pós-Operatórias/etiologia , Fatores de Risco
13.
Arq Bras Cardiol ; 92(2): 116-26, 2009 02.
Artigo em Inglês, Português, Espanhol | MEDLINE | ID: mdl-19360244

RESUMO

BACKGROUND: Pulmonary hypertension (PH) is a factor of poor prognosis in the postoperative period of heart transplant (HT) and thus, the study of the degree of reversibility to vasodilators is mandatory during the preoperative assessment. OBJECTIVE: To evaluate the pulmonary and systemic hemodynamic effects of sildenafil as a vasodilator during the PH reversibility test in patients that are candidates to HT. METHODS: Patients awaiting HT were submitted to the measurement of systemic and pulmonary hemodynamic variables before and after the administration of a single sublingual dose of 100 mg of sildenafil during right heart catheterization. RESULTS: Fourteen patients (age: 47+/-12 years, 71.4% men) with advanced heart failure Ejection Fraction (EF) 25 +/- 7%, Functional Class (FC - NYHA) FC III - 6 and FC IV - 8, were evaluated in this study. The acute administration of sildenafil showed to be effective in decreasing the systolic (62.4 +/- 12.1 vs 51.5 +/- 9.6 mmHg, CI=95%, p<0.05) and mean (40.7 +/- 7.3 vs 33.8 +/- 7.6 mmHg, CI=95%, p <0.05) pressures of the pulmonary artery. There was also a significant decrease in the pulmonary (4.2 +/- 3 vs 2.0 +/- 0.9 uWood, CI=95%, p<0.05) and systemic vascular resistance (22.9 +/- 6.8 vs 18.6 +/- 4.1 Wood, CI=95%, p<0.05), associated to an increase in the cardiac output (3.28 +/- 0.79 vs 4.12 +/-1.12 uWood, CI=95%, p<0.05) without, however, significantly interfering in the systemic arterial pressure (87.8 +/- 8.2 vs 83.6 +/- 9.1 mmHg, CI=95%, p=0.3). CONCLUSION: The sublingual administration of sildenafil is an effective and safe alternative as a vasodilator during the PH reversibility test in patients with heart failure and awaiting a HT.


Assuntos
Insuficiência Cardíaca , Hipertensão Pulmonar/tratamento farmacológico , Piperazinas/administração & dosagem , Sulfonas/administração & dosagem , Vasodilatadores/administração & dosagem , Administração Sublingual , Feminino , Insuficiência Cardíaca/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Transplante de Coração , Humanos , Hipertensão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Purinas/administração & dosagem , Citrato de Sildenafila
14.
Arq. bras. cardiol ; 92(2): 122-126, fev. 2009. graf, tab
Artigo em Português | LILACS | ID: lil-511103

RESUMO

FUNDAMENTO: A hipertensão pulmonar (HP) é fator de mau prognóstico no pós-operatório de transplante cardíaco (TC) e, desta forma, o estudo do grau de reversibilidade a vasodilatadores é obrigatório durante avaliação pré-operatória. OBJETIVO: Avaliar os efeitos hemodinâmicos pulmonares e sistêmicos do sildenafil como droga vasodilatadora durante o teste de reversibilidade da HP em candidatos a transplante cardíaco. MÉTODOS: Pacientes em fila para TC foram submetidos à medida de variáveis hemodinâmicas sistêmicas e pulmonares antes e após a administração de 100mg dose única e sublingual de sildenafil, durante cateterização cardíaca direita. RESULTADOS: Quatorze pacientes (idade: 47±12 anos, 71,4 por cento homens) com insuficiência cardíaca avançada, Fração de Ejeção (FE) 25 ± 7 por cento, Classe Funcional (CF- NYHA) CF III - 6 e CF IV - 8, foram avaliados neste estudo. A administração aguda de sildenafil mostrou ser eficaz na redução das pressões sistólica (62,4 ± 12,1 vs. 51,5 ± 9,6 mmHg, IC=95 por cento, p<0,05) e média (40,7 ± 7,3 vs. 33,8 ± 7,6 mmHg, IC=95 por cento, p <0,05) da artéria pulmonar. Houve também uma redução significativa da resistência vascular pulmonar (4,2 ± 3 vs. 2,0 ± 0,9 uWood, IC=95 por cento, p<0,05) e sistêmica (22,9 ± 6,8 vs. 18,6 ± 4,1 Wood, IC=95 por cento, p<0,05), associada a uma elevação do débito cardíaco (3,28 ± 0,79 vs. 4,12 ±1,12 uWood, IC=95 por cento, p<0,05) sem, no entanto, interferir de maneira significativa na pressão arterial sistêmica (87,8 ± 8,2 vs. 83,6 ± 9,1 mmHg, IC=95 por cento, p=0,3). CONCLUSÃO: O sildenafil sublingual é uma alternativa eficaz e segura como droga vasodilatadora durante o teste de reversibilidade da HP em portadores de insuficiência cardíaca e em fila para transplante cardíaco.


BACKGROUND: Pulmonary hypertension (PH) is a factor of poor prognosis in the postoperative period of heart transplant (HT) and thus, the study of the degree of reversibility to vasodilators is mandatory during the preoperative assessment. OBJECTIVE: To evaluate the pulmonary and systemic hemodynamic effects of sildenafil as a vasodilator during the PH reversibility test in patients that are candidates to HT. METHODS: Patients awaiting HT were submitted to the measurement of systemic and pulmonary hemodynamic variables before and after the administration of a single sublingual dose of 100 mg of sildenafil during right heart catheterization. RESULTS: Fourteen patients (age: 47±12 years, 71.4 percent men) with advanced heart failure Ejection Fraction (EF) 25 ± 7 percent, Functional Class (FC - NYHA) FC III - 6 and FC IV - 8, were evaluated in this study. The acute administration of sildenafil showed to be effective in decreasing the systolic (62.4 ± 12.1 vs 51.5 ± 9.6 mmHg, CI=95 percent, p<0.05) and mean (40.7 ± 7.3 vs 33.8 ± 7.6 mmHg, CI=95 percent, p <0.05) pressures of the pulmonary artery. There was also a significant decrease in the pulmonary (4.2 ± 3 vs 2.0 ± 0.9 uWood, CI=95 percent, p<0.05) and systemic vascular resistance (22.9 ± 6.8 vs 18.6 ± 4.1 Wood, CI=95 percent, p<0.05), associated to an increase in the cardiac output (3.28 ± 0.79 vs 4.12 ±1.12 uWood, CI=95 percent, p<0.05) without, however, significantly interfering in the systemic arterial pressure (87.8 ± 8.2 vs 83.6 ± 9.1 mmHg, CI=95 percent, p=0.3). CONCLUSION:The sublingual administration of sildenafil is an effective and safe alternative as a vasodilator during the PH reversibility test in patients with heart failure and awaiting a HT.


FUNDAMENTO: La hipertensión pulmonar (HP) se muestra factor de mal pronóstico en el postoperatorio de transplante cardiaco (TC) y, de esta forma, el estudio del grado de reversibilidad a vasodilatadores se vuelve obligatorio durante evaluación preoperatoria. OBJETIVO: Evaluar los efectos hemodinámicos pulmonares y sistémicos del Sildenafil como droga vasodilatadora durante la prueba de reversibilidad de la HP en candidatos a transplante cardiaco. MÉTODOS: Pacientes en fila para TC fueron sometidos a la medición de variables hemodinámicas sistémicas y pulmonares, antes y luego de la administración de 100mg en dosificación única y sublingual de Sildenafil, durante cateterización cardiaca derecha. RESULTADOS: Se evaluaron en este estudio a 14 pacientes (edad: 47±12 años, el 71,4 por ciento varones) con insuficiencia cardiaca avanzada, fracción de eyección (FE) 25 ± 7 por ciento, clase funcional (CF-NYHA) CF III - 6 y CF IV - 8. La administración aguda de Sildenafil se mostró eficaz en la reducción de las presiones sistólica (62,4 ± 12,1 vs 51,5 ± 9,6 mmHg, IC=95 por ciento, p<0,05) y media (40,7 ± 7,3 vs 33,8 ± 7,6 mmHg, IC=95 por ciento, p <0,05) de la arteria pulmonar. Hubo también una reducción significativa de la resistencia vascular pulmonar (4,2 ± 3 vs 2,0 ± 0,9 uWood, IC=95 por ciento, p<0,05) y sistémica (22,9 ± 6,8 vs 18,6 ± 4,1 Wood, IC=95 por ciento, p<0,05), asociada a una elevación del débito cardiaco (3,28 ± 0,79 vs 4,12 ±1,12 uWood, IC=95 por ciento, p<0,05) sin, con todo, interferir de manera significativa en la presión arterial sistémica (87,8 ± 8,2 vs 83,6 ± 9,1 mmHg, IC=95 por ciento, p=0,3). CONCLUSIÓN: El Sildenafil sublingual resulta una alternativa eficaz y segura como droga vasodilatadora durante la prueba de reversibilidad de la HP en portadores de insuficiencia cardiaca y en fila para transplante cardiaco.


Assuntos
Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Cardíaca , Hipertensão Pulmonar/tratamento farmacológico , Piperazinas/administração & dosagem , Sulfonas/administração & dosagem , Vasodilatadores/administração & dosagem , Administração Sublingual , Transplante de Coração , Insuficiência Cardíaca/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Hipertensão Pulmonar/fisiopatologia , Purinas/administração & dosagem
15.
Rev Bras Cir Cardiovasc ; 24(4): 453-62, 2009 Oct-Dec.
Artigo em Inglês, Português | MEDLINE | ID: mdl-20305917

RESUMO

OBJECTIVES: With the increase in life expectancy occurred in recent decades, it has been noted the concomitant increase in the prevalence of aortic stenosis and degenerative disease of atherosclerotic coronary artery. This study aims to evaluate the influence of atherosclerotic coronary artery disease in patients with critical aortic stenosis undergoing isolated or combined implant valve prosthesis and coronary artery by pass grafting. METHODS: In the period of January 2001 to March 2006, there were analyzed 448 patients undergoing isolated implant aortic valve prosthesis (Group I) and 167 patients undergoing aortic valve prosthesis implant combined with coronary artery bypass grafting (Group II). Pre- and intra-operative variables elected for analysis were: age, gender, body mass index, stroke, diabetes mellitus, chronic obstructive pulmonary disease, rheumatic fever, hypertension, endocarditis, acute myocardial infarction, smoking, Fraction of the left ventricular ejection, critical atherosclerotic coronary artery disease, chronic atrial fibrillation, aortic valve operation prior (conservative), functional class of congestive heart failure, value serum creatinine, total cholesterol, size of the prosthesis used, length and number of distal anastomoses held in myocardial revascularization, duration of cardiopulmonary bypass and aortic clamping time. The statistical study employed invariant and multivariate analysis. RESULTS: Hospital mortality was 14.3% (64 deaths) in Group I, and 14.5% (58 deaths) in patients with atherosclerotic coronary artery disease associated criticism (Group IB) and 12.8% (six deaths) in which had this association (Group IA). Hospital mortality in Group II was 17.6% (29 deaths), and 16.1% (20 deaths) in patients undergoing implantation of prosthetic aortic valve combined to complete myocardial revascularization (Group II) and 20.9% (nine deaths) in the myocardial revascularization with incomplete (Group IIB). CONCLUSIONS: In patients undergoing implant isolated from aortic valve prosthesis, the presence of atherosclerotic coronary artery disease associated critical in at least two arteries, influenced the hospital mortality. In patients undergoing surgical treatment combined the number of coronary arteries with critical atherosclerotic disease and extent of coronary artery bypass grafting (complete or incomplete), did not affect the hospital mortality, but the realization of more than three anastomoses in the distal myocardial revascularization interfered.


Assuntos
Estenose da Valva Aórtica/cirurgia , Ponte de Artéria Coronária , Doença da Artéria Coronariana/cirurgia , Implante de Prótese de Valva Cardíaca , Mortalidade Hospitalar , Complicações Pós-Operatórias/mortalidade , Estenose da Valva Aórtica/mortalidade , Terapia Combinada , Doença da Artéria Coronariana/mortalidade , Métodos Epidemiológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Fatores de Risco
16.
Rev Bras Cir Cardiovasc ; 23(1): 7-13, 2008 Jan-Mar.
Artigo em Português | MEDLINE | ID: mdl-18719822

RESUMO

OBJECTIVE: This study aims to evaluate the effects of prophylactic heart donor tricuspid annuloplasty in patients after heart transplantation with bicaval anastomosis. METHODS: From 2002 to 2005, 20 patients undergoing heart transplantation with bicaval anastomosis and with a survival rate over 6 months were deliberately selected. Patients were divided into two groups: Group I - 10 patients who underwent prophylactic heart donor tricuspid annuloplasty by the De Vega technique; and Group II - 10 patients did not undergo annuloplasty. In both groups, presurgical clinical characteristics were the same. The tricuspid regurgitation degree was evaluated by transthoracic Doppler echocardiography and it was qualified from 0 to 3 (0=absent, 1=mild, 2=moderated, 3=severe). Myocardial performance was evaluated by ventricular ejection fraction and invasive hemodynamic study performed during routine endomyocardial biopsies. RESULTS: Mean clinical follow-up was 14.6+/-4.3 (6 and 16) months. There was only one death in group II. It was not related to annuloplasty. Mean degree of tricuspid regurgitation in Group I was 0.4+/-0.6 and in Group II was 1.6+/-0.8 (p < 0.05). There was a statistically significant difference between both groups in right atrium pressure, which was higher in Group II. CONCLUSIONS: In view of the limitations of the study, the prophylactic tricuspid annuloplasty in heart donor reduced the degree of valvar regurgitation in the medium term after heart transplantation with bicaval anastomosis, in spite of not interfering with the allograft hemodynamic performance in the period under consideration.


Assuntos
Transplante de Coração/métodos , Complicações Pós-Operatórias/prevenção & controle , Insuficiência da Valva Tricúspide/cirurgia , Valva Tricúspide/cirurgia , Adolescente , Adulto , Anastomose Cirúrgica , Feminino , Seguimentos , Humanos , Hipertensão Pulmonar/complicações , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Doadores de Tecidos , Insuficiência da Valva Tricúspide/prevenção & controle , Adulto Jovem
17.
Rev. bras. cir. cardiovasc ; 23(1): 7-13, jan.-mar. 2008. ilus, tab
Artigo em Inglês, Português | LILACS | ID: lil-489693

RESUMO

OBJETIVO: O presente estudo tem por objetivo avaliar os efeitos da anuloplastia tricúspide profilática no coração doador em transplante cardíaco com anastomose bicaval. MÉTODOS: De 2002 a 2005, foram selecionados de forma não aleatória 20 pacientes submetidos ao transplante cardíaco pela técnica bicaval e com sobrevida superior a seis meses. Eles foram divididos em dois grupos: Grupo I - 10 pacientes que receberam coração doador com anuloplastia tricúspide profilática, pela técnica de De Vega; e Grupo II - 10 pacientes que não receberam a anuloplastia, ambos com características semelhantes. O grau de regurgitação tricúspide foi avaliado pela ecocardiografia transtorácica com Doppler e foi quantificado entre 0 e 3 (0=ausente, 1=discreto, 2=moderado, 3=grave). O desempenho miocárdico foi avaliado pela fração de ejeção ventricular e pelo estudo hemodinâmico invasivo, durante as biópsias endomiocárdicas de rotina. RESULTADOS: O período médio de observação foi de 14,6±4,3 meses (6 e 16 meses). Houve apenas um óbito no grupo II não relacionado à anuloplastia. O grau médio de regurgitação tricúspide no Grupo I foi de 0,4±0,6 e no Grupo II foi de 1,6±0,8 (p < 0,05). Dentre as variáveis analisadas, houve apenas diferença estatisticamente significativa na pressão do átrio direito do Grupo II, que foi maior. CONCLUSÕES: Respeitando-se as limitações do estudo, podese observar que a anuloplastia tricúspide no coração doador reduz a regurgitação em médio prazo após o transplante cardíaco pela técnica bicaval, a despeito de não interferir no desempenho hemodinâmico do enxerto, no período considerado.


OBJECTIVE: This study aims to evaluate the effects of prophylactic heart donor tricuspid annuloplasty in patients after heart transplantation with bicaval anastomosis. METHODS: From 2002 to 2005, 20 patients undergoing heart transplantation with bicaval anastomosis and with a survival rate over 6 months were deliberately selected. Patients were divided into two groups: Group I - 10 patients who underwent prophylactic heart donor tricuspid annuloplasty by the De Vega technique; and Group II - 10 patients did not undergo annuloplasty. In both groups, presurgical clinical characteristics were the same. The tricuspid regurgitation degree was evaluated by transthoracic Doppler echocardiography and it was qualified from 0 to 3 (0=absent, 1=mild, 2=moderated, 3=severe). Myocardial performance was evaluated by ventricular ejection fraction and invasive hemodynamic study performed during routine endomyocardial biopsies. RESULTS: Mean clinical follow-up was 14.6±4.3 (6 and 16) months. There was only one death in group II. It was not related to annuloplasty. Mean degree of tricuspid regurgitation in Group I was 0.4±0.6 and in Group II was 1.6±0.8 (p < 0.05). There was a statistically significant difference between both groups in right atrium pressure, which was higher in Group II. CONCLUSIONS: In view of the limitations of the study, the prophylactic tricuspid annuloplasty in heart donor reduced the degree of valvar regurgitation in the medium term after heart transplantation with bicaval anastomosis, in spite of not interfering with the allograft hemodynamic performance in the period under consideration.


Assuntos
Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Transplante de Coração/métodos , Complicações Pós-Operatórias/prevenção & controle , Insuficiência da Valva Tricúspide/cirurgia , Valva Tricúspide/cirurgia , Anastomose Cirúrgica , Seguimentos , Hipertensão Pulmonar/complicações , Estudos Retrospectivos , Doadores de Tecidos , Insuficiência da Valva Tricúspide/prevenção & controle , Adulto Jovem
18.
In. Serrano Junior, Carlos V; Tarasoutchi, Flávio; Jatene, Fábio B.; Mathias Junior, Wilson. Cardiologia baseada em relatos de casos. São Paulo, Manole, 2006. p.379-381, ilus.
Monografia em Português | LILACS | ID: lil-441413
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