Beneficial Roles of Cellulose Patch-Mediated Cell Therapy in Myocardial Infarction: A Preclinical Study.

Biological scaffolds have become an attractive approach for repairing the infarcted myocardium and have been shown to facilitate constructive remodeling in injured tissues. This study aimed to investigate the possible utilization of bacterial cellulose (BC) membrane patches containing cocultured cells to limit myocardial postinfarction pathology. Myocardial infarction (MI) was induced by ligating the left anterior descending coronary artery in 45 Wistar rats, and patches with or without cells were attached to the hearts. After one week, the animals underwent echocardiography to assess for ejection fraction and left ventricular end-diastolic and end-systolic volumes. Following patch formation, the cocultured cells retained viability of >90% over 14 days in culture. The patch was applied to the myocardial surface of the infarcted area after staying 14 days in culture. Interestingly, the BC membrane without cellular treatment showed higher preservation of cardiac dimensions; however, we did not observe improvement in the left ventricular ejection fraction of this group compared to coculture-treated membranes. Our results demonstrated an important role for BC in supporting cells known to produce cardioprotective soluble factors and may thus provide effective future therapeutic outcomes for patients suffering from ischemic heart disease.

Expanded CD133+ Cells from Human Umbilical Cord Blood Improved Heart Function in Rats after Severe Myocardial Infarction.

Pharmacological approaches are partially effective in limiting infarct size. Cell therapies using a cell population enriched with endothelial progenitor cells (EPCs) CD133+ have opened new perspectives for the treatment of ischemic areas after infarction. This preclinical study evaluated the effect of intramyocardial transplantation of purified or expanded human umbilical cord blood-derived CD133+ cells on the recovery of rats following acute myocardial infarction (AMI). Histology studies, electrocardiogram, and fluorescence in situ hybridization (FISH) were used to evaluate heart recovery. Purified CD133+ cells, enriched in endothelial progenitor cells, when expanded in vitro acquired an endothelial-like cell phenotype expressing CD31 and von Willebrand factor (vWF). The group of infarcted rats that received expanded CD133+ cells had a more significant recovery of contraction performance and less heart remodeling than the group that received purified CD133+ cells. Either purified or expanded CD133+ cells were able to induce neovascularization in the infarcted myocardium in an equivalent manner. Few human cells were detected in the infarcted myocardium of the rats 28 days after transplantation suggesting that the effects observed might be related primarily to paracrine activity. Although both cell populations ameliorated the infarcted heart and are suitable for regeneration of the vascular system, expanded CD133+ cells are more beneficial and promising candidates for vascular regeneration.

Comparison of two surgical techniques for creating an acute myocardial infarct in rats / Comparação de duas técnicas cirúrgicas para criar um infarto agudo do miocárdio em ratos

Objective: To perform a comparative assessment of two surgical techniques that are used creating an acute myocardial infarc by occluding the left anterior descending coronary artery in order to generate rats with a left ventricular ejection fraction of less than 40%. Methods: The study was completely randomized and comprised 89 halothane-anaesthetised rats, which were divided into three groups. The control group (SHAM) comprised fourteen rats, whose left anterior descending coronary artery was not occluded. Group 1 (G1): comprised by 35 endotracheally intubated and mechanically ventilated rats, whose left anterior descending coronary artery was occluded. Group 2 (G2): comprised 40 rats being manually ventilated using a nasal respirator whose left anterior descending coronary artery was occluded. Other differences between the two techniques include the method of performing the thoracotomy and removing the pericardium in order to expose the heart, and the use of different methods and suture types for closing the thorax. Seven days after surgery, the cardiac function of all surviving rats was determined by echocardiography. Results: No rats SHAM group had progressed to death or had left ventricular ejection fraction less than 40%. Nine of the 16 surviving G1 rats (56.3%) and six of the 20 surviving G2 rats (30%) had a left ventricular ejection fraction of less than 40%. Conclusion: The results indicate a tendency of the technique used in G1 to be better than in G2. This improvement is probably due to the greater duration of the open thorax, which reduces the pressure over time from the surgeon, allowing occlusion of left anterior descending coronary artery with higher accuracy. .

Objetivo: Realizar uma avaliação comparativa de duas técnicas cirúrgicas que são usadas para criar um infarto agudo do miocárdio pela oclusão da artéria coronária descendente anterior esquerda, a fim de gerar ratos com uma fração de ejeção ventricular esquerda inferior a 40%. Métodos: O estudo foi completamente randomizado e composto por 89 ratos anestesiados com halotano, que foram divididos dentro de três grupos. O grupo controle (SHAM) composto por 14 ratos, cuja artéria coronária descendente anterior esquerda não foi ocluída. Grupo 1 (G1): composto por 35 ratos intubados endotraquealmente e ventilados mecanicamente, cuja artéria coronária descendente anterior esquerda foi ocluída. Grupo 2 (G2): constituído por 40 ratos sendo ventilados manualmente utilizando um respirador nasal, cuja artéria coronária descendente anterior esquerda foi ocluída. Outras diferenças entre as duas técnicas incluem o método de realizar a toracotomia e remover o pericárdio, a fim de expor o coração, e o uso de diferentes métodos e tipos de sutura para fechar o tórax. Sete dias após a cirurgia, a função cardíaca de todos os ratos sobreviventes foi determinada por ecocardiografia. Resultados: Nenhum rato do grupo SHAM foi a óbito ou teve fração de ejeção ventricular esquerda menor que 40%. Nove dos 16 ratos sobreviventes do G1 (56,3%) e seis dos 20 ratos sobreviventes do G2 (30%) tiveram uma fração de ejeção ventricular esquerda inferior a 40%. Conclusão: Os resultados indicam uma tendência da técnica utilizada no G1 ser melhor do que a do G2. Esta melhora deve-se provavelmente à maior duração do tórax aberto, o que reduz a pressão de tempo sobre o cirurgião, permitindo uma oclusão da artéria coronária descendente anterior esquerda com maior acurácia. .

Comparison of two surgical techniques for creating an acute myocardial infarct in rats.

OBJECTIVE: To perform a comparative assessment of two surgical techniques that are used creating an acute myocardial infarc by occluding the left anterior descending coronary artery in order to generate rats with a left ventricular ejection fraction of less than 40%. METHODS: The study was completely randomized and comprised 89 halothane-anaesthetised rats, which were divided into three groups. The control group (SHAM) comprised fourteen rats, whose left anterior descending coronary artery was not occluded. Group 1 (G1): comprised by 35 endotracheally intubated and mechanically ventilated rats, whose left anterior descending coronary artery was occluded. Group 2 (G2): comprised 40 rats being manually ventilated using a nasal respirator whose left anterior descending coronary artery was occluded. Other differences between the two techniques include the method of performing the thoracotomy and removing the pericardium in order to expose the heart, and the use of different methods and suture types for closing the thorax. Seven days after surgery, the cardiac function of all surviving rats was determined by echocardiography. RESULTS: No rats SHAM group had progressed to death or had left ventricular ejection fraction less than 40%. Nine of the 16 surviving G1 rats (56.3%) and six of the 20 surviving G2 rats (30%) had a left ventricular ejection fraction of less than 40%. CONCLUSION: The results indicate a tendency of the technique used in G1 to be better than in G2. This improvement is probably due to the greater duration of the open thorax, which reduces the pressure over time from the surgeon, allowing occlusion of left anterior descending coronary artery with higher accuracy.

Efeito do exercício associado ao transplante de células-tronco sobre a função ventricular de ratos pós-infarto agudo do miocárdio / Effect of exercise associated with stem cell transplantation on ventricular function in rats after acute myocardial infarction

OBJETIVO: Avaliar o efeito da associação terapêutica entre o transplante autólogo de células-tronco e o exercício físico aquático, sobre a fração de ejeção do ventrículo esquerdo (FEVE) de ratos com disfunção ventricular pós-infarto agudo do miocárdio (IAM). MÉTODOS: Foram induzidos ao IAM, por ligadura da artéria coronária esquerda, 21 ratos Wistar. Os animais foram submetidos à ecocardiografia para avaliação da FEVE (%) e dos volumes diastólico e sistólico finais do ventrículo esquerdo (VDF, VSF, ml), randomizados e ao transplante das células-tronco mononucleares. Os animais foram divididos em quatro grupos: grupo sedentário sem células (n=5), sedentário com células (n=5), treinado sem células (n=5) e treinado com células (n=6). O treinamento físico foi iniciado 30 dias após o IAM e realizado em piscina adaptada durante 30 dias. No início e no final do protocolo de treinamento físico, foram realizadas dosagens de lactato. Os animais foram submetidos a nova ecocardiografia após 60 dias do IAM. RESULTADOS: Comparação dos valores de FEVE 30 dias e 60 dias pós-IAM, respectivamente: sedentário sem (35,20 ± 7,64% vs. 22,39 ± 4,56% P=0,026), com células (25,18 ± 7,73% vs. 23,85 ± 9,51% P=0,860) e no treinado sem (21,49 ± 2,70% vs. 20,71 ± 7,14% P=0,792), treinado com células (28,86 ± 6,68 vs. 38,43 ±7,56% P=0,062). Identificou-se a diminuição de fibras colágenas, nas regiões de fibrose miocárdica no grupo treinado com e sem células. CONCLUSÃO: A associação terapêutica entre exercício físico e o transplante autólogo de células-tronco foi benéfica contra as ações do remodelamento ventricular.

OBJECTIVE: To analyze the functional and anatomical-pathological effect of transplantation of bone marrow mononuclear cells associated to aquatic physical activity after myocardial infarction in rats. METHODS: Twenty-one rats were induced by myocardial infarction, through left coronary artery ligation. After a week, the animals were subjected to echocardiography for evaluation of left ventricle ejection fraction (LVEF, %) and dyastolic and end systolic volume of the left ventricle (EDV, ESV, ml), randomized and the transplantation of mononuclear stem cells. The animals were divided into four groups: sedentary group without cells (n=5), sedentary with cells (n=5), trained without cells (n=5) and trained with cells (n=6). The physical training was started 30 days after infarction and held in swimming during 30 days. At the beginning and at the end of the physical training protocol were held assay of lactate. The animals have been subjected to new echocardiography after 60 days of myocardial infarction. RESULTS: Two months after the transplant, were observed decrease in FE in the control group (35.2 to 23.54 P=0.022) and addition of LVEF and stabilization of ventricular remodeling in the group trained with cells (29.85 to 33.43% P=0.062 and 0.71 to 0.73 ml, P=0.776, respectively). Identified the reduction of collagen fibers, myocardial fibrosis regions in the group trained with and without cells. CONCLUSION: The group trained with cells improves ventricular function compared to the control group, suggesting the benefit of associated cell therapy will physical activity.

Effect of exercise associated with stem cell transplantation on ventricular function in rats after acute myocardial infarction.

OBJECTIVE: To analyze the functional and anatomical-pathological effect of transplantation of bone marrow mononuclear cells associated to aquatic physical activity after myocardial infarction in rats. METHODS: Twenty-one rats were induced by myocardial infarction, through left coronary artery ligation. After a week, the animals were subjected to echocardiography for evaluation of left ventricle ejection fraction (LVEF, %) and dyastolic and end systolic volume of the left ventricle (EDV, ESV, ml), randomized and the transplantation of mononuclear stem cells. The animals were divided into four groups: sedentary group without cells (n=5), sedentary with cells (n=5), trained without cells (n=5) and trained with cells (n=6). The physical training was started 30 days after infarction and held in swimming during 30 days. At the beginning and at the end of the physical training protocol were held assay of lactate. The animals have been subjected to new echocardiography after 60 days of myocardial infarction. RESULTS: Two months after the transplant, were observed decrease in FE in the control group (35.2 to 23.54 P=0.022) and addition of LVEF and stabilization of ventricular remodeling in the group trained with cells (29.85 to 33.43% P=0.062 and 0.71 to 0.73 ml, P=0.776, respectively). Identified the reduction of collagen fibers, myocardial fibrosis regions in the group trained with and without cells. CONCLUSION: The group trained with cells improves ventricular function compared to the control group, suggesting the benefit of associated cell therapy will physical activity.

Análise Doppler ecocardiográfica fetal de gestantes portadoras de diabete melito gestacional / Fetal Doppler ecocardiography analysis of pregnant with gestational diabetes mellitus

Objetivo: Avaliar dados Doppler- ecocardiográfico fetal, em gestantes portadoras de diabete melito gestacional (DMG). Método: Estudo prospectivo descritivo, realizado no período de abril de 2.007 a março de 2.008. Foram avaliados 68 fetos de gestantes portadoras de DMG. com idade gestacional entre 22 e 37 semanas. As variáveis analisadas foram: características epidemiológicas maternas relativas ao DMG e parâmetros do Doppler-ecocardiograma fetal. Resultados: A prevalência de hipertrofia miocárdica foi de 27,9%. Os fetos com hipertrofia miocárdica (HMC) apresentaram idade gestacional menor (29,3 versus 32,0 semanas p< 0,05) e circunferência abdominal menor (5,3% versus 40,8% p< 0,05), no momento do exame; as outras características epidemiológicas não apresentaram diferença. Quanto às alterações funcionais, encontramos fração de encurtamento normal emtodos e disfunção diastólica em 3 (15,8%) fetos com HMC (p< 0,05) e dois (4,15%) sem HMC. O índice de performance miocárdica, tanto do ventrículo direito (0,57+-0,13) como no esquerdo (0,58+-0,17) apresentaram valores aumentados no terceiro trimestre de gestação em relação a séries históricas. Não encontramos correlação positiva entre HMC e onda A, onda E do fluxo transvalvar mitral, índice de performance miocárdica do ventrículo direito e do ventrículo esquerdo. Conclusões: Foi encontrado HMC em 27,9% dos fetos, destes 21% apresentaram disfunção diastólica. A fração de encurtamento foi normal em todos os fetos avaliados. Os outros parâmetros avaliados não apresentaram correlação com HMC.

Objective: To evaluate data from fetal Doppler echocardiography performed in pregnant patients with gestational diabetes mellitus (GDM). Methods: This is a prospective, descriptive study carried out from April 2007 to March 2008. Sixty-eight fetuses withgestational age ranging from 22 to 37 weeks, from pregnant patients presenting GDM were analyzed. Variables analyzed were maternal GDM-related epidemiological characteristics and settings from fetal Doppler echocardiography. Results: Prevalence rate of myocardial hypertrophy was 27.9%. Fetuses with myocardial hypertrophy (MCH) presented lower gestational age (29.3 vs. 32.0 weeks p<0.05) and smaller abdominal circumference (5.3% vs. 40.8% p<0.05) upon examination. Other epidemiological characteristics presented no difference. Regarding functional alterations, normal shortening fraction measurements were found inall fetuses. Diastolic dysfunction was found in three fetuses (15.8%) with MCH (p< 0,05) and two (4.15%) without MCH. The myocardial performance index both from the right ventricle and from the left ventricle showed higher values in the third trimester of gestation, in comparison with a historic trend. No positive correlation was found between MCH and A wave, E wave from mitral transvalve volume flow or myocardial performance index from the right or from the left ventricle. Conclusion: MCH was found in 27.9% of fetuses, of which 21% presented diastolic dysfunction. The shortening fraction measurement was normal in all fetuses analyzed. No correlation between MCH and the other parameters analyzed was found.

Disfunção do homoenxerto pulmonar utilizado na reconstrução do trato de saída do ventrículo direito / Dysfunction of the pulmonary homograft used in the reconstruction of the right ventricle exit tract / Disfunción del homoinjerto pulmonar utilizado en la reconstrucción del tracto de salida del ventrículo derecho

FUNDAMENTO: O homoenxerto pulmonar tem sido utilizado como uma opção na correção de cardiopatia congênita com obstrução da via de saída do ventrículo direito. Os resultados em longo prazo, no entanto, mostram-se pouco satisfatórios. OBJETIVO: Identificar os fatores de risco associados à disfunção e à falência do homoenxerto pulmonar. MÉTODOS: Estudo em crianças submetidas à ampliação da via de saída do ventrículo direito com homoenxerto pulmonar. As variáveis clínicas, cirúrgicas, evolutivas e de aspectos morfológicos da prótese foram analisadas como fatores de risco. RESULTADOS: A amostra final de 75 pacientes com idade mediana na cirurgia de 22 meses, variando de 1-157 meses, apresentou 13 pacientes (17,0 por cento) que desenvolveram disfunção do homoenxerto, caracterizado por estenose ou insuficiência pulmonar grave. O tempo de ocorrência entre o implante do homoenxerto e a detecção da disfunção foi de 45 ± 20 meses. Quando o tamanho do homoenxerto foi menor de 21 mm e o escore Z da valva pulmonar foi menor do que zero, ou maior do que três, foram considerados fatores de risco para a ocorrência de disfunção. CONCLUSÃO: O homoenxerto pulmonar de tamanho menor do que 21 mm e a valva pulmonar inadequada para idade e peso do paciente são fatores determinantes para disfunção da prótese.

BACKGROUND: The pulmonary homograft has been used as an option in the correction of congenital cardiopathy with obstruction of the right ventricle exit tract. The long term results, however, are little satisfactory. OBJECTIVE: Identify the risk factors associated to the dysfunction and the pulmonary homograft failure. METHODS: Study with children submitted to the enlargement of the exit tract of the right ventricle with pulmonary homograft. The clinical, surgical, evolutional and morphological aspects of the prosthesis variables were analyzed as risk factors. RESULTS: The final sample of 75 patients with median age at the surgery of 22 months, varying from 1-157 months, presented 13 patients (17.0 percent) who developed dysfunction of the homograft, characterized by stenosis or severe pulmonary insufficiency. The occurrence time between the homograft implant and the detection of the dysfunction was of 45 ± 20 months. When the size of the homograft was smaller than 21 mm and the Z score of the pulmonary valva is lower than zero, or higher than three, the risk factors were considered for the dysfunction occurrence. CONCLUSION: The pulmonary homograft smaller than 21 mm and the inadequate pulmonary valva for the age and weight of the patient are determining factors for the prosthesis dysfunction.

FUNDAMENTO: El homoinjerto pulmonar ha sido utilizado como una opción en la corrección de cardiopatía congénita con obstrucción de la vía de salida del ventrículo derecho. Los resultados a largo plazo, mientras tanto, se muestran poco satisfactorios. OBJETIVO: Identificar los factores de riesgo asociados a la disfunción y a la falla del homoinjerto pulmonar. MÉTODOS: Estudio en niños sometidos a la ampliación de la vía de salida del ventrículo derecho con homoinjerto pulmonar. Las variables clínicas, quirúrgicas, evolutivas y de aspectos morfológicos de la prótesis fueron analizadas como factores de riesgo. RESULTADOS: La muestra final de 75 pacientes con edad mediana en la cirugía de 22 meses, variando de 1-157 meses, presentó 13 pacientes (17,0 por ciento) que desarrollaron disfunción del homoinjerto, caracterizado por estenosis o insuficiencia pulmonar grave. El tiempo de ocurrencia entre el implante del homoinjerto y la detección de la disfunción fue de 45 ± 20 meses. Cuando el tamaño del homoinjerto fue menor de 21 mm y el escore Z de la válvula pulmonar fue menor que cero, o mayor que tres, fueron considerados factores de riesgo para la ocurrencia de disfunción. CONCLUSIÓN: El homoinjerto pulmonar de tamaño menor que 21 mm y la válvula pulmonar inadecuada para edad y peso del paciente son factores determinantes para disfunción de la prótesis.

Dysfunction of the pulmonary homograft used in the reconstruction of the right ventricle exit tract.

BACKGROUND: The pulmonary homograft has been used as an option in the correction of congenital cardiopathy with obstruction of the right ventricle exit tract. The long term results, however, are little satisfactory. OBJECTIVE: Identify the risk factors associated to the dysfunction and the pulmonary homograft failure. METHODS: Study with children submitted to the enlargement of the exit tract of the right ventricle with pulmonary homograft. The clinical, surgical, evolutional and morphological aspects of the prosthesis variables were analyzed as risk factors. RESULTS: The final sample of 75 patients with median age at the surgery of 22 months, varying from 1-157 months, presented 13 patients (17.0%) who developed dysfunction of the homograft, characterized by stenosis or severe pulmonary insufficiency. The occurrence time between the homograft implant and the detection of the dysfunction was of 45 ± 20 months. When the size of the homograft was smaller than 21 mm and the Z score of the pulmonary valva is lower than zero, or higher than three, the risk factors were considered for the dysfunction occurrence. CONCLUSION: The pulmonary homograft smaller than 21 mm and the inadequate pulmonary valva for the age and weight of the patient are determining factors for the prosthesis dysfunction.

Transplantation of SNAP-treated adipose tissue-derived stem cells improves cardiac function and induces neovascularization after myocardium infarct in rats.

Stem cell therapy has been considered a promise for damaged myocardial tissue. We have previously shown that S-nitroso-N-acetyl-D,L-penicillamine (SNAP) increases the expression of several muscular markers and VEGF in mesenchymal stem cells, indicating that transplantation of SNAP-treated cells could provide better functional outcomes. Here, we transplanted SNAP-treated adipose tissue-derived stem cells (ADSCs) in rat infarcted myocardium. After 30days, we observed a significant improvement of the ejection fraction in rats that received SNAP-treated ADSCs, compared with those that received untreated cells (p=0.008). Immunohistochemical reactions showed an increased expression of troponin T-C and von Willebrand factor, and organized vascular units in the infarcted area of tissue transplanted with treated ADSCs. SNAP exposure induced intracellular S-nitrosation, a decreased GSH/GSSG ratio, but did not increase cGMP levels. Collectively, these results indicate that SNAP alters the redox environment of ADSCs, possibly associated with a pre-differentiation state, which may improve cardiac function after transplantation.

Evaluation of the biological behavior of decellularized pulmonary homografts: an experimental sheep model.

INTRODUCTION: The cryopreserved homograft is a good valve substitute due attributes like excellent hemodynamics, low incidence of thromboembolic events, infection resistance and good mid-term durability. However, progressive homograft degeneration and fibrocalcification may occur, particularly in the childhood and young adults. Their antigenicity triggers an immunological reaction that plays an important role in their degeneration and failure. The decellularization process was proposed to decrease this antigenicity. By the action of detergents and enzymes, this process removes all cellular components from the homograft matrix, diminishing immunogenicity and probably delaying its degeneration. OBJECTIVE: The objective of this experimental and descriptive study is to evaluate the biological and functional behavior of decellularized pulmonary homografts (Decell-H), treated by a sodium dodecil sulfate solution (0.1%), developed in our University (Pontifícia Universidade Católica do Paraná). For the characterization of Decell-H performance, parameters like recellularization, calcification, and echocardiographic data will be analyzed. METHODS: Eight juvenile sheep were submitted to the implantation of the Decell-H sutured into orthotopic position, through a left thoracotomy and with cardiopulmonary bypass support. They were followed-up clinically and by periodical echocardiograms until the explantation, which were performed in different time for every two sheep: seven, 30, 90 and 180 postoperative days. For histological analysis we used Hematoxilin-eosin, Movat and Alizarin-Red staining. RESULTS: The sheep reached their follow-up period in a good clinical state. There was no valve regurgitation or stenonis by the echocardiogram. The animals submitted to the explantation in 90 and 180 days had a significant somatic growth and these Decell-H(s) had a diameter increase, without central valve insufficiency. Histologically, all homografts preserved their extra-cellular matrix organization and were progressively recellularized, without calcification. CONCLUSION: In this experimental model, the Decell-H behaved as an excellent valve substitute.

Avaliação do comportamento biológico de homoenxertos valvares pulmonares descelularizados: estudo experimental em ovinos / Evaluation of the biological behavior of decellularized pulmonary homografts: an experimental sheep model

INTRODUÇÃO: Não havendo um substituto valvar ideal, os homoenxertos criopreservados são considerados uma boa opção, pelo excelente perfil hemodinâmico, baixa incidência de tromboembolismo, resistência a infecções e durabilidade a médio prazo. Porém, estão sujeitos à progressiva degeneração, especialmente em crianças e adultos jovens. Sua antigenicidade desencadeia uma resposta imunológica que contribui para sua degeneração, calcificação e falência. Para diminuir esta antigenicidade, desenvolveu-se o processo de descelularização. Pela ação de detergentes e enzimas, este processo remove os componentes celulares do homoenxerto, diminuindo sua imunogenicidade e, provavelmente, retardando sua degeneração. OBJETIVO: O objetivo deste estudo, experimental e descritivo, é analisar o comportamento histológico e funcional de homoenxertos pulmonares ovinos descelularizados (H-descel) por uma nova solução, composta principalmente de dodecil sulfato de sódio a 0,1 por cento e desenvolvida na PUCPR. Para caracterizar este comportamento, serão avaliados o repovoamento celular, a ocorrência de calcificação e a função valvar ao ecocardiograma. MÉTODOS: A amostra foi constituída de oito ovinos, submetidos ao implante de H-descel em posição ortotópica, através de uma toracotomia esquerda, com auxílio de circulação extracorpórea. Os animais foram acompanhados clinicamente e por ecocardiogramas periódicos até o explante, realizados em prazos predefinidos para cada dois animais: sete, 30, 90 e 180 dias. A análise histológica foi realizada por colorações Hematoxilina-eosina, Pentacrômio de Movat e Alizarina Red. RESULTADOS: Todos os animais sobreviveram ao procedimento e atingiram seus períodos de seguimento. Não houve insuficiência ou estenose destes enxertos ao ecocardiograma. Os animais submetidos aos explantes em 90 e 180 dias tiveram significativos ganhos ponderais e estes H-descel aumentaram de diâmetro, sem desenvolver insuficiência. À histologia, todos mantiveram a organização de sua matriz extracelular, foram progressivamente repovoados e não apresentaram calcificação. CONCLUSÃO: Neste modelo experimental, os H-descel mostraram-se excelentes substitutos valvares a médio prazo.

INTRODUCTION: The cryopreserved homograft is a good valve substitute due attributes like excellent hemodynamics, low incidence of thromboembolic events, infection resistance and good mid-term durability. However, progressive homograft degeneration and fibrocalcification may occur, particularly in the childhood and young adults. Their antigenicity triggers an immunological reaction that plays an important role in their degeneration and failure. The decellularization process was proposed to decrease this antigenicity. By the action of detergents and enzymes, this process removes all cellular components from the homograft matrix, diminishing immunogenicity and probably delaying its degeneration. OBJECTIVE: The objective of this experimental and descriptive study is to evaluate the biological and functional behavior of decellularized pulmonary homografts (Decell-H), treated by a sodium dodecil sulfate solution (0.1 percent), developed in our University (Pontifícia Universidade Católica do Paraná). For the characterization of Decell-H performance, parameters like recellularization, calcification, and echocardiographic data will be analyzed. METHODS: Eight juvenile sheep were submitted to the implantation of the Decell-H sutured into orthotopic position, through a left thoracotomy and with cardiopulmonary bypass support. They were followed-up clinically and by periodical echocardiograms until the explantation, which were performed in different time for every two sheep: seven, 30, 90 and 180 postoperative days. For histological analysis we used Hematoxilin-eosin, Movat and Alizarin-Red staining. RESULTS: The sheep reached their follow-up period in a good clinical state. There was no valve regurgitation or stenonis by the echocardiogram. The animals submitted to the explantation in 90 and 180 days had a significant somatic growth and these Decell-H(s) had a diameter increase, without central valve insufficiency. Histologically, all homografts preserved their extra-cellular matrix organization and were progressively recellularized, without calcification. CONCLUSION: In this experimental model, the Decell-H behaved as an excellent valve substitute.

Hospital mortality in surgery for reconstruction outflow right ventricle with pulmonary homograft.

BACKGROUND: Hospital mortality for surgical reconstruction of the outflow of the right ventricle with pulmonary homograft is variable. OBJECTIVES: To identify risk factors associated with hospital mortality and clinical profile of patients. METHODS: Children underwent reconstruction of the outflow tract of right ventricle with pulmonary homograft. Analyzed as risk factors for the clinical, surgical and morphological aspects of the prosthesis. RESULTS: Ninety-two patients operated on between 1998 and 2005 presented mainly pulmonary atresia with ventricular septal defect and tetralogy of Fallot. Forty patients were treated in the first month of life. He needed 38 surgeries to Blalock Taussig due to clinical severity. The median age at surgery for total correction was 22 months, ranging from 1 to 157 months. Size pulmonary homograft ranging from 12 to 26 mm and length of bypass was 132 +/- 37 minutes. After surgery there were seventeen deaths (18% cases) on average 10.5 +/- 7.5 days. The predominant cause was multiple organ failure. In the univariate analysis between the types of heart disease, they found in favor of age at surgery, size of homograft, pulmonary valve Z value, CPB time, maintaining the integrity of the homograft and pulmonary tree change. There was no statistical difference in hospital mortality between the variables and the type of heart disease. CONCLUSION: The congenital obstructive right requires surgical care in the first days of life. The total correction surgery has a risk rate of 18% but there was no association with any variable studied.

Drenagem anômala total das veias pulmonares: 29 anos de experiência em uma única instituição / Total anomalous pulmonary venous drainage: 29 years of experience in a single institution

FUNDAMENTO: A drenagem anômala total das veias pulmonares (DATVP) é uma doença rara, com incidência aproximada de 0,058 a 0,083:1.000 nascidos vivos. Apresenta mortalidade em torno de 80 por cento a 90 por cento no primeiro ano de vida, se não tratada precocemente. OBJETIVO: Utilizando a experiência de 29 anos de um único serviço, foram testadas possíveis variáveis relacionadas ao óbito hospitalar. MÉTODOS: Análise retrospectiva de 123 pacientes consecutivos operados com o diagnóstico de DATVP entre janeiro de 1979 e março de 2008. Foram incluídos apenas pacientes com DATVP isolada, excluídas as associações complexas. As variáveis foram testadas para a identificação da influência sobre os óbitos e da interferência da evolução temporal. RESULTADOS: As medianas de peso e idade foram de 4,1 kg e 120 dias, respectivamente. O subtipo anatômico supracardíaco foi o mais prevalente em todo o período analisado. Obstrução à drenagem esteve presente em 30 por cento dos casos, sendo o subtipo infracardíaco o mais associado. A taxa de mortalidade geral foi de 27 por cento, chegando a zero nos últimos cinco anos. Tanto na análise univariada quanto na multivariada, a presença de obstrução ao fluxo venoso pulmonar foi a única variável positivamente associada aos óbitos (p=0,005), independentemente da evolução temporal. A mortalidade dentre estes casos foi de 44 por cento. CONCLUSÃO: Após três décadas de evolução, pode-se observar melhora na mortalidade precoce da drenagem anômala total das veias pulmonares em nosso serviço, que atualmente apresenta níveis consistentes com a literatura. A obstrução à drenagem pulmonar continua sendo fator de mau prognóstico em nosso meio.

BACKGROUND: Total anomalous pulmonary venous drainage (TAPVD) is a rare disease, with an approximate incidence of 0.058 to 0.083:1,000 live births. It has a mortality rate of around 80 percent to 90 percent in the first year, if not treated early. OBJECTIVE: Using the 29-year experience of a single center, possible variables related to hospital death were tested. METHODS: Retrospective analysis of 123 consecutive patients with a diagnosis of TAPVD that underwent surgical treatment between January 1979 and March 2008. Only patients with isolated TAPVD were included and the complex associations were excluded. The variables were tested for the identification of their influence on death and of the interference of temporal evolution. RESULTS: The medians of weight and age were 4.1 kg and 120 days, respectively. The supracardiac anatomic subtype was the most prevalent throughout the analyzed period. Obstruction to drainage was present in 30 percent of the cases and the infracardiac subtype was the most frequently associated form. The general mortality rate was 27 percent, being equal to zero in the last five years. At both the univariate and multivariate analysis, the presence of obstruction to pulmonary venous flow was the only variable positively associated to the deaths (p = 0,005), regardless of the temporal evolution. The mortality among these cases was 44 percent. CONCLUSION: After three decades of evolution, an improvement in the early mortality rate of TAPVD can be observed in our service, which currently presents levels consistent with the literature. The obstruction to pulmonary drainage is still a bad prognostic factor in our country.

Are purified or expanded cord blood-derived CD133+ cells better at improving cardiac function?

Endothelial progenitor cells (EPCs), which express the CD133 marker, can differentiate into mature endothelial cells (ECs) and create new blood vessels. Normal angiogenesis is unable to repair the injured tissues that result from myocardial infarction (MI). Patients who have high cardiovascular risks have fewer EPCs and their EPCs exhibit greater in vitro senescence. Human umbilical cord blood (HUCB)-derived EPCs could be an alternative to rescue impaired stem cell function in the sick and elderly. The aim of this study was to purify HUCB-derived CD133(+) cells, expand them in vitro and evaluate the efficacy of the purified and expanded cells in treating MI in rats. CD133(+) cells were selected for using CD133-coupled magnetic microbeads. Purified cells stained positive for EPC markers. The cells were expanded and differentiated in media supplemented with fetal calf serum and basic fibroblast growth factor, insulin-like growth factor-I and vascular endothelial growth factor (VEGF). Differentiation was confirmed by lack of staining for EPC markers. These expanded cells exhibited increased expression of mature EC markers and formed tubule-like structures in vitro. Only the expanded cells expressed VEGF mRNA. Cells were expanded up to 70-fold during 60 days of culture, and they retained their functional activity. Finally, we evaluated the therapeutic potential of purified and expanded CD133(+) cells in treating MI by intramyocardially injecting them into a rat model of MI. Rats were divided into three groups: A (purified CD133(+) cells-injected); B (expanded CD133(+) cells-injected) and C (saline buffer-injected). We observed a significant improvement in left ventricular ejection fraction for groups A and B. In summary, CD133(+) cells can be purified from HUCB, expanded in vitro without loosing their biological activity, and both purified and expanded cells show promising results for use in cellular cardiomyoplasty. However, further pre-clinical testing should be performed to determine whether expanded CD133(+) cells have any clinical advantages over purified CD133(+) cells.

[Total anomalous pulmonary venous drainage: 29 years of experience in a single institution]. / Drenagem anômala total das veias pulmonares: 29 anos de experiência em uma única instituição.

BACKGROUND: Total anomalous pulmonary venous drainage (TAPVD) is a rare disease, with an approximate incidence of 0.058 to 0.083:1,000 live births. It has a mortality rate of around 80% to 90% in the first year, if not treated early. OBJECTIVE: Using the 29-year experience of a single center, possible variables related to hospital death were tested. METHODS: Retrospective analysis of 123 consecutive patients with a diagnosis of TAPVD that underwent surgical treatment between January 1979 and March 2008. Only patients with isolated TAPVD were included and the complex associations were excluded. The variables were tested for the identification of their influence on death and of the interference of temporal evolution. RESULTS: The medians of weight and age were 4.1 kg and 120 days, respectively. The supracardiac anatomic subtype was the most prevalent throughout the analyzed period. Obstruction to drainage was present in 30% of the cases and the infracardiac subtype was the most frequently associated form. The general mortality rate was 27%, being equal to zero in the last five years. At both the univariate and multivariate analysis, the presence of obstruction to pulmonary venous flow was the only variable positively associated to the deaths (p = 0,005), regardless of the temporal evolution. The mortality among these cases was 44%. CONCLUSION: After three decades of evolution, an improvement in the early mortality rate of TAPVD can be observed in our service, which currently presents levels consistent with the literature. The obstruction to pulmonary drainage is still a bad prognostic factor in our country.

[Clinical profile of systemic inflammatory response after pediatric cardiac surgery with cardiopulmonary bypass]. / Perfil clínico da resposta inflamatória sistêmica após cirurgia cardíaca pediátrica com circulação extracorpórea.

BACKGROUND: the postoperative period of congenital cardiomyopathies correction is frequently accompanied by systemic inflammatory response. OBJECTIVE: To assess the frequency of occurrence and clinical manifestations of the systemic inflammatory response syndrome after cardiopulmonary bypass (SIRS-CPB) in children submitted to cardiac surgery. METHODS: Historical cohort study including patients up to 3 years old that were submitted to elective corrective surgeries for congenital cardiopathies with cardiopulmonary bypass (CPB). A total of 101 patients were assessed by means of clinical criteria of organ dysfunction through score tests, as comparing predisponent factors and aggregated morbidity to the presence of SIRS-CPB. RESULTS: Twenty-two patients (21.9%) fulfilled the criteria for SIRS-CPB. The sex or type of cardiopathy did not differ between groups (p = NS). Patients diagnosed with SIRS-CPB (compared to patients without SIRS-CPB) presented lower mean age (6.8 +/- 5.5 versus 10.8 +/- 5.1 months, p < 0.05), lower weight (5.3 +/- 1.9 versus 6.9 +/- 2.0 kg, p < 0.05), and longer CPB duration (125.1 +/- 49.5 versus 93.9 +/- 33.1 minutes, p < 0.05). Longer median duration of mechanical ventilation (120.0 versus 13.0 hours, p < 0.05), longer stay in Intensive Care Unit (ICU) (265.0 versus 107.0 hours, p < 0.05) and in hospital (22.0 versus 10.0 days, p < 0.05) were observed. In the multivariate analysis, higher weight (OR = 0.68, p = 0.01) was identified as a protection factor. CONCLUSION: The adopted clinical criteria identified a risk group for SIRS-CPB, which presented lower weight and longer CPB duration as predisponent factors. Patients with SIRS-CPB remain in mechanical ventilation, in ICU and in hospitalization for a longer period of time.

Mortalidade hospitalar na cirurgia de reconstrução da via de saída do ventrículo direito com homeonxerto pulmonar / Hospital mortality in surgery for reconstruction outflow right ventricle with pulmonary homograft

FUNDAMENTO: Mortalidade hospitalar na cirurgia de reconstrução da via de saída do ventrículo direito com homoenxerto pulmonar é variável. OBJETIVOS: Identificar os fatores de risco associados à mortalidade hospitalar e ao perfil clínico dos pacientes. MÉTODOS: Estudo de crianças submetidas à reconstrução da via de saída do ventrículo direito com homoenxerto pulmonar. Analisados como fatores de risco as variáveis clínicas, cirúrgicas e de aspectos morfológicos da prótese. RESULTADOS: Noventa e dois pacientes foram operados entre 1998 e 2005, apresentando principalmente atresia pulmonar com comunicação interventricular e a tetralogia de Fallot. Quarenta pacientes foram atendidos no primeiro mês de vida. Necessitaram de 38 cirurgias de Blalock Taussig devido à gravidade clínica. A idade mediana na cirurgia de correção total foi de 22 meses, variando de 1 mês a 157 meses. O tamanho homoenxerto pulmonar variou de 12 a 26 mm e o tempo de extracorpórea foi 132 ± 37 minutos. Após a cirurgia houve 17 óbitos (18 por cento casos), em média 10,5 ± 7,5 dias após. A causa predominante foi falência de múltiplos órgãos. Na análise univariada entre os tipos de cardiopatia, estas deferiram na idade, momento da cirurgia, tamanho do homoenxerto, valor Z da valva pulmonar, tempo de circulação extracorpórea, manutenção da integridade do homoenxerto e alteração da árvore pulmonar. Não houve diferença estatística com relação à mortalidade hospitalar entre as variáveis e o tipo de cardiopatia. CONCLUSÃO: As cardiopatias obstrutivas do lado direito necessitam de atendimento cirúrgico nos primeiros dias de vida. A cirurgia de correção total apresenta risco de mortalidade de 18 por cento, mas não houve associação com nenhuma variável estudada.

BACKGROUND: Hospital mortality for surgical reconstruction of the outflow of the right ventricle with pulmonary homograft is variable. OBJECTIVES: To identify risk factors associated with hospital mortality and clinical profile of patients. METHODS: Children underwent reconstruction of the outflow tract of right ventricle with pulmonary homograft. Analyzed as risk factors for the clinical, surgical and morphological aspects of the prosthesis. RESULTS: Ninety-two patients operated on between 1998 and 2005 presented mainly pulmonary atresia with ventricular septal defect and tetralogy of Fallot. Forty patients were treated in the first month of life. He needed 38 surgeries to Blalock Taussig due to clinical severity. The median age at surgery for total correction was 22 months, ranging from 1 to 157 months. Size pulmonary homograft ranging from 12 to 26 mm and length of bypass was 132 ± 37 minutes. After surgery there were seventeen deaths (18 percent cases) on average 10.5 ± 7.5 days. The predominant cause was multiple organ failure. In the univariate analysis between the types of heart disease, they found in favor of age at surgery, size of homograft, pulmonary valve Z value, CPB time, maintaining the integrity of the homograft and pulmonary tree change. There was no statistical differencein hospital mortality between the variables and the type of heart disease. CONCLUSION: The congenital obstructive right requires surgical care in the first days of life. The total correction surgery has a risk rate of 18 percent but there was no association with any variable studied.

Perfil clínico da resposta inflamatória sistêmica após cirurgia cardíaca pediátrica com circulação extracorpórea / Clinical profile of systemic inflammatory response after pediatric cardiac surgery with cardiopulmonary bypass / Perfil clínico de la respuesta inflamatoria sistémica tras cirugía cardiaca pediátrica con circulación extracorpórea

Fundamento: O pós-operatório de correção de cardiopatias congênitas frequentemente é acompanhado por resposta inflamatória sistêmica. Objetivo: Avaliar a frequência e as manifestações clínicas da síndrome de resposta inflamatória sistêmica após circulação extracorpórea (SRIS-CEC) em crianças submetidas à cirurgia cardíaca. Métodos: Coorte histórico incluindo pacientes com até 3 anos de idade, submetidos à correção cirúrgica eletiva de cardiopatias congênitas com utilização de circulação extracorpórea (CEC). Foram analisados 101 pacientes por meio de critérios clínicos de disfunção de órgãos sob forma de escore, comparando-se fatores predisponentes e morbidade agregada à presença de SRIS-CEC. Resultados: Foram identificados 22 pacientes (21,9 por cento) que preencheram os critérios estabelecidos para SRIS-CEC. O sexo ou tipo de cardiopatia não diferiu entre os grupos (p =NS). Pacientes com SRIS-CEC (comparados aos pacientes sem SRIS-CEC) apresentavam idade média menor (6,8 ± 5,5 vs. 10,8 ± 5,1 meses, p < 0,05), menor peso (5,3 ± 1,9 vs. 6,9 ± 2,0 quilogramas, p < 0,05), maior tempo CEC (125,1 ± 49,5 vs. 93,9 ± 33,1 minutos, p < 0,05). Observou-se respectivamente maior tempo em mediana de ventilação mecânica (120,0 vs. 13,0 horas, p < 0,05), maior tempo de internação em unidade de cuidados intensivos (UCI) (265,0 vs. 107,0 horas, p < 0,05) e internação hospitalar (22,0 vs. 10,0 dias, p < 0,05). Em análise multivariada, maior peso (OR = 0,68, p = 0,01) foi identificado como fator de proteção. Conclusão: Os critérios clínicos adotados identificaram um grupo de risco para SRIS-CEC. Esse grupo tem como fatores predisponentes: menor peso e maior tempo de CEC. Pacientes com SRIS-CEC permanecem maior tempo em ventilação mecânica, internados em unidade de cuidados intensivos e em hospital.

Background: the postoperative period of congenital cardiomyopathies correction is frequently accompanied by systemic inflammatory response. Objective: To assess the frequency of occurrence and clinical manifestations of the systemic inflammatory response syndrome after cardiopulmonary bypass (SIRS-CPB) in children submitted to cardiac surgery. Methods: Historical cohort study including patients up to 3 years old that were submitted to elective corrective surgeries for congenital cardiopathies with cardiopulmonary bypass (CPB). A total of 101 patients were assessed by means of clinical criteria of organ dysfunction through score tests, as comparing predisponent factors and aggregated morbidity to the presence of SIRS-CPB. Results: Twenty-two patients (21.9 percent) fulfilled the criteria for SIRS-CPB. The sex or type of cardiopathy did not differ between groups (p = NS). Patients diagnosed with SIRS-CPB (compared to patients without SIRS-CPB) presented lower mean age (6.8 ± 5.5 versus 10.8 ± 5.1 months, p < 0.05), lower weight (5.3 ± 1.9 versus 6.9 ± 2.0 kg, p < 0.05), and longer CPB duration (125.1 ± 49.5 versus 93.9 ± 33.1 minutes, p < 0.05). Longer median duration of mechanical ventilation (120.0 versus 13.0 hours, p < 0.05), longer stay in Intensive Care Unit (ICU) (265.0 versus 107.0 hours, p < 0.05) and in hospital (22.0 versus 10.0 days, p < 0.05) were observed. In the multivariate analysis, higher weight (OR = 0.68, p = 0.01) was identified as a protection factor. Conclusion: The adopted clinical criteria identified a risk group for SIRS-CPB, which presented lower weight and longer CPB duration as predisponent factors. Patients with SIRS-CPB remain in mechanical ventilation, in ICU and in hospitalization for a longer period of time.

Fundamento: El postoperatorio de corrección de cardiopatías congénitas está acompañado frecuentemente por una respuesta inflamatoria sistémica. Objetivo: Evaluar la frecuencia y las manifestaciones clínicas del síndrome de respuesta inflamatoria sistémica tras la circulación extracorpórea (SRIS-CEC) en niños sometidos a una cirugía cardiaca. Métodos: Cohorte histórica de pacientes con hasta 3 años de edad, sometidos a la corrección quirúrgica electiva de cardiopatías congénitas con utilización de circulación extracorpórea (CEC). Fueron analizados 101 pacientes mediante criterios clínicos de disfunción de órganos bajo forma de escore, comparando factores predisponentes y morbilidad agregada a la presencia de SRIS-CEC. Resultados: Fueron identificados 22 pacientes (21,9 por ciento) que cumplieron los criterios establecidos para el SRIS-CEC. El sexo o tipo de cardiopatía no difirió entre los grupos (p =NS). Pacientes con SRIS-CEC (comparados a los pacientes sin SRIS-CEC) presentaban un menor promedio de edad (6,8 ± 5,5 vs 10,8 ± 5,1 meses, p < 0,05), menor peso (5,3 ± 1,9 vs 6,9 ± 2,0 kilogramos, p < 0,05), mayor tiempo de CEC (125,1 ± 49,5 vs 93,9 ± 33,1 minutos, p < 0,05). Se observó respectivamente mayor tiempo promedio de ventilación mecánica (120,0 vs 13,0 horas, p < 0,05), mayor tiempo de internación en unidad de cuidados intensivos (UCI) (265,0 vs 107,0 horas, p < 0,05) e internación hospitalaria (22,0 vs 10,0 días, p < 0,05). En el análisis multivariado, el mayor peso (OR = 0,68, p = 0,01) fue identificado como factor de protección. Conclusión: Los criterios clínicos adoptados identificaron un grupo de riesgo para SRIS-CEC. Ese grupo tiene como factores predisponentes: menor peso y mayor tiempo de CEC. Pacientes con SRIS-CEC permanecen mayor tiempo en ventilación mecánica, internados en unidad de cuidados intensivos y en hospital.

Prenatal diagnosis of left ventricular aneurysm and diverticulum.

We report two cases of localized left ventricular (LV) protrusion, an entity that has been described in the literature as aneurysm or diverticulum. Both cases had different outcomes from those previously reported. Little is known on the incidence and natural history of these rare anomalies, whose progression may be asymptomatic or lead to severe complications and death in the prenatal period. The therapeutic approach should be customized.