Incidencia y factores asociados a infección en el primer año postrasplante cardiaco

Objetivo: Determinar la incidencia de las infecciones en el primer año postrasplante cardiaco y los factores asociados a las infecciones en este periodo. Materiales y métodos: Estudio analítico de casos y controles anidados en una cohorte, con los pacientes trasplantados cardiacos en la Fundación Cardioinfantil – Instituto de cardiología desde el año 2005 hasta el 2015. Se realizaron análisis univariados, análisis bivariado entre las variables del estudio y el desenlace para la selección de las variables para el modelo de regresión logística. Resultados: Se presentó una mediana de 54 años de edad en la cohorte, con mayor proporción de hombres (75,8%) y con predominio de la cardiopatía dilatada como indicación de trasplante. La incidencia de infecciones en el primer año postrasplante fue de 45% (30/66). Se encontró mayor riesgo de infección en los primeros tres meses, del 36.3% (IC 95% 23 – 55), mostrando mayor frecuencia de infecciones pulmonares y en piel. Dentro de los organismos aislados más importantes en los primeros tres meses, se encontraron bacilos gram negativos y Aspergillus spp. En el primer año postrasplante la cardiopatía dilatada con un OR 4.7 IC95% (1.3 – 17) y la enfermedad renal crónica con un OR 6.7 IC 95% (1.4 - 32) se asociaron a la presencia de infecciones. Conclusiones: La frecuencia de infecciones en los pacientes trasplantados cardiacos en la Fundación Cardioinfantil IC es similar a la observada en la literatura. La aparición de infecciones en el primer año postrasplante, se asocia a la presencia de cardiopatía dilatada y enfermedad renal crónica.

Coxsackievirus B3-associated myocardial pathology and viral load reduced by recombinant soluble human decay-accelerating factor in mice

Coxsackievirus B3 (CVB3) infection can result in myocarditis, which in turn may lead to a protracted immune response and subsequent dilated cardiomyopathy. Human decay-accelerating factor (DAF), a binding receptor for CVB3, was synthesized as a soluble IgG1-Fc fusion protein (DAF-Fc). In vitro, DAF-Fc was able to inhibit complement activity and block infection by CVB3, although blockade of infection varied widely among strains of CVB3. To determine the effects of DAF-Fc in vivo, 40 adolescent A/J mice were infected with a myopathic strain of CVB3 and given DAF-Fc treatment 3 days before infection, during infection, or 3 days after infection; the mice were compared with virus alone and sham-infected animals. Sections of heart, spleen, kidney, pancreas, and liver were stained with hematoxylin and eosin and submitted to in situ hybridization for both positive-strand and negative-strand viral RNA to determine the extent of myocarditis and viral infection, respectively. Salient histopathologic features, including myocardial lesion area, cell death, calcification and inflammatory cell infiltration, pancreatitis, and hepatitis were scored without knowledge of the experimental groups. DAF-Fc treatment of mice either preceding or concurrent with CVB3 infection resulted in a significant decrease in myocardial lesion area and cell death and a reduction in the presence of viral RNA. All DAF-Fc treatment groups had reduced infectious CVB3 recoverable from the heart after infection. DAF-Fc may be a novel therapeutic agent for active myocarditis and acute dilated cardiomyopathy if given early in the infectious period, although more studies are needed to determine its mechanism and efficacy.

Inhibitory Signals Mediated by Programmed Death-1 Are Involved With T-Cell Function in Chronic Periodontitis

Background: Inhibitory signals mediated via molecules such as programmed death-1 (PD-1) play a critical role in downmodulating immune responses and maintaining peripheral tolerance. We investigated the involvement of cytokines and PD-1 engagement in mediating the T-cell unresponsiveness to bacterial and ubiquitous antigens in periodontal diseases. Methods: Gingival and peripheral blood samples from healthy individuals and patients with chronic periodontitis were collected and used for the subsequent assays. Leukocytes in the lesion site and blood were evaluated using flow cytometry. The production of interferon-gamma, interleukin-10, and transforming growth factor-P proteins was evaluated by enzyme-linked immunosorbent assay (ELISA), and the presence of PD-1+cells in the inflamed gingiva was confirmed by immunofluorescence confocal microscopy for CD4 and PD-1 colocalization. Results: T cells from patients with chronic periodontitis proliferated poorly in response to Aggregatibacter actinomycetem comitans (previously Actinobacillus actinomycetemcomitans) antigen. T-cell unresponsiveness was not associated with imbalanced cytokine production. However, T cells from patients with chronic periodontitis expressed significantly higher levels of PD-1 either upon isolation or after culture with antigens. Moreover, PD-1 blocking did not result in significant T-cell proliferation in cells cultured with phytohemagglutinin or bacterial antigens. The blockade of PD-1 resulted in the increased production of IFN-gamma. In addition, CD4+ and CD8+ T cells expressing PD-1 accumulated in lesions with chronic periodontitis. Conclusion: These data show that PD-1 engagement could be involved in the modulation of IFN-gamma production by T cells in patients with chronic periodontitis. J Periodontol 2009,80:1833-1844.

Estudo da função ventricular na técnica de plicatura da parede livre do ventrículo esquerdo em cães

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Alterações ecocardiográficas em cães sob tratamento prolongado com doxorrubicina

Avaliou-se a cardiotoxicidade da doxorrubicina utilizando-se sete cães adultos, clinicamente normais, que receberam 30mg/m² de cloridrato de doxorrubicina (Adriblastina®) por via intravenosa, a cada 21 dias, durante 168 dias (grupo A), perfazendo dose cumulativa total de 240mg/m². em outros sete cães (grupo B) administraram-se 5ml de solução salina 0,9% estéril por via intravenosa, seguindo-se o esquema de aplicação proposto anteriormente. Os animais foram avaliados, periodicamente, por meio de exames ecocardiográficos em modo-M e bidimensional. Verificou-se aumento (P<0,01) no diâmetro e volume do ventrículo esquerdo, inicialmente em sístole e, posteriormente, em diástole, hipocinesia do septo interventricular e da parede livre do ventrículo esquerdo, reduções de aproximadamente 65% nas frações de encurtamento e de ejeção, além de aumento da separação do septo do ponto E do folheto anterior da válvula mitral nos animais do grupo A. As alterações cardíacas decorrentes do tratamento crônico com doxorrubicina foram semelhantes àquelas descritas em cães com cardiomiopatia dilatada, e os índices ecocardiográficos puderam ser utilizados no acompanhamento e na prevenção da cardiotoxicidade pelo quimioterápico.

Tratamento de insuficiência cardíaca com benazepril em cães com cardiomiopatia dilatada e endocardiose

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Repercussões hemodinâmicas do posicionamento em litotomia exagerada para histerectomia vaginal em paciente cardiopata: relato de caso

JUSTIFICATIVA E OBJETIVOS: A técnica de histerectomia vaginal possibilita menor tempo operatório e o uso do bloqueio do neuro-eixo, com os benefícios de melhor analgesia pós-operatória e menor resposta sistêmica ao procedimento cirúrgico. O objetivo deste relato foi descrever as alterações hemodinâmicas decorrentes do posicionamento em litotomia exagerada em paciente cardiopata. RELATO do CASO: Paciente de 33 anos, G0P0A0, com história de sangramento uterino anormal e anemia. A ultra-sonografia evidenciava útero miomatoso com volume estimado de 420 cm³. Ela era portadora de trombofilia e miocardiopatia dilatada, com passado de dois acidentes vasculares encefálicos isquêmicos e dois infartos agudos do miocárdio. Foi monitorizada com pressão arterial invasiva e cateter de artéria pulmonar com medida de débito cardíaco contínuo. Realizada raquianestesia com bupivacaína hiperbárica e morfina. A paciente foi posicionada em litotomia exagerada sendo realizada histerectomia total pela técnica de Heaney e salpingectomia bilateral. Como intercorrência intra-operatória apresentou diminuição do índice cardíaco e aumento das pressões de câmaras direitas após o posicionamento, necessitando do uso de dobutamina. CONCLUSÕES: O posicionamento em litotomia exagerada pode ocasionar alterações hemodinâmicas que devem ser consideradas na escolha da técnica cirúrgica.

Pre- and post-transplant anti-myosin and anti-heat shock protein antibodies and cardiac transplant outcome

Background: the purpose this study was to investigate the relationship of anti-myosin and anti-heat shock protein immunoglobulin G (IgG) serum antibodies to the original heart disease of cardiac transplant recipients, and also to rejection and patient survival after cardiac transplantation.Methods: Anti-myosin and anti-heat shock protein (anti-hsp) IgG antibodies were evaluated in pre-transplant sera from 41 adult cardiac allograft recipients and in sequential post-transplant serum samples from 11 recipients, collected at the time of routine endomyocardial biopsies during the first 6 months after transplantation. In addition, the levels of these antibodies were determined from the sera of 28 healthy blood donors.Results: Higher anti-myosin antibody levels were observed in pre-transplant sera than in sera from normal controls. Moreover, patients with chronic Chagas heart disease showed higher anti-myosin levels than patients with ischemic heart disease, and also higher levels, although not statistically significant, than patients with dilated cardiomyopathy. Higher anti-hsp levels were also observed in patients compared with healthy controls, but no significant differences were detected among,the different types of heart diseases. Higher pre-transplant anti-myosin, but not anti-hsp, levels were associated with lower 2-year post-transplant survival. In the post-transplant period, higher anti-myosin IgG levels were detected in sera collected during acute rejection than in sera collected during the rejection-free period, whereas anti-hsp IgG levels showed no difference between these periods.Conclusions: the present findings are of interest for post-transplant management and, in addition, suggest a pathogenic role for anti-myosin antibodies in cardiac transplant rejection, as has been proposed in experimental models of cardiac transplantation.

Relações pressão-diâmetro e esforço-diâmetro do ventrículo esquerdo em seres humanos. Padronização e análise crítica do método.

PURPOSE--To provide a critical analysis of the fluid filled manometric system and M-mode echocardiography and, by their association, to standardize the determination of left ventricular (LV) pressure-diameter and stress-diameter relationships in humans. MATERIAL AND METHODS--The pressure curve and the LV M-mode image was obtained in 24 patients with cardiopathy. The dynamic characteristics of the fluid-filled system have been studied to define the amplitude, the resonance and the time gap of the pressure curve register. The delay of the pressure curve recording was determined in all cases by comparing pressure curve and echocardiographic aortic valve registers. The values of pressure, diameter, posterior wall thickness and LV meridional stress was calculated at every 0.02s. RESULTS--Preliminary analyses of the fluid-filled manometric system indicated that this system has variable dynamic characteristics. The pressure-diameter and stress-diameter loops obtained were similar to those of the literature. The values of end-systolic stress, percentage of fractional shortening, ejection fraction and circumferential fiber shortening rate of patients with dilated cardiomyopathy (n = 5) were significantly reduced when compared to the values of patients without left ventricular overload (n = 8) and patients with ventricular volume overload. It has been verified, also, that the retard of the pressure curve record introduced by the fluid-filled manometric system does not modify the values of these variables. CONCLUSION--The LV pressure-diameter and stress-diameter relationships obtained by the association of echocardiography and LV manometry showed functional characteristics of the ventricle that could not appear by the use of the echocardiography or by the LV manometry themselves.

Reduction of diameter of the left ventricle of dogs by plication of the left ventricular free wall

Objective - To determine effects of reducing the diameter of the left ventricle of dogs by plication of the left ventricular free wall. Animals - 8 healthy adult mixed-breed dogs. Procedure - Left lateral thoracotomy and a T-shaped pericardiotomy were performed. The free wall of the left ventricle was imbricated with 3 interrupted transfixing sutures applied in a horizontal mattress pattern, using 3-0 polypropylene suture assembled on a straight cutting needle. Surgeons were careful to avoid the coronary vessels. Echocardiography was performed 24 hours before and 48 hours after surgery. Electrocardiography was performed before and 1, 2, 7, 15, 21, 30, and 60 days after surgery. Results - Echocardiographic measurements revealed that the diameter of the left ventricle was reduced by a mean of 23.5%. Electrocardiography revealed ventricular premature complexes 24 hours after surgery that regressed without treatment during the first week after surgery. Conclusions and Clinical Relevance - Plication of the left ventricular free wall of dogs can reduce end-diastolic and end-systolic dimensions of the left ventricle. The technique is simple and does not require cardiopulmonary bypass. According to Laplace's law, the reduction of cardiac diameter leads to reduction on free-wall tension and may improve left ventricular function in dilatated hearts. Thus, additional studies involving dogs with dilated cardiomyopathy should be conducted.

Neurohormonal, hemodynamic, and electrocardiographic evaluations of healthy dogs receiving long-term administration of doxorubicin

Objective - To evaluate diagnostic testing that could be used to establish an early diagnosis of cardiotoxicosis induced by long-term administration of doxorubicin. Animals - 13 adult mixed-breed dogs. Procedures - 7 dogs were administered doxorubicin chloride (30 mg/m2, IV, q 21 d for 168 days [cumulative dose, 240 mg/m2]), and 6 dogs received saline (0.9% NaCl) solution (5 mL, IV, q 21 d for 168 days; control group). Echocardiography, ECG, arterial blood pressure, plasma renin activity (PRA), and plasma concentrations of norepinephrine and brain natriuretic peptide (BNP) were assessed before each subsequent administration of doxorubicin and saline solution. Results - Dogs that received doxorubicin had a significant decrease in R-wave amplitude, compared with values for the control group, from 30 to 210 mg/m2. Doxorubicin-treated dogs had decreases in fractional shortening and left ventricular ejection fraction evident as early as 30 mg/m2, but significant differences between groups were not detected until 90 mg/m2 was reached. There was also a significant increase in PRA (≥ 120 mg/m2) and left ventricular end-systolic and end-diastolic dimensions (≥ 60 and ≥ 180 mg/m2, respectively). Systemic arterial pressure, remaining echocardiographic variables, and concentrations of norepinephrine and BNP had significant variations, but of no clinical importance, during doxorubicin administration. Conclusions and clinical relevance - Doxorubicin-induced cardiotoxicosis developed at 120 mg/m2, but there were no clinical signs of dilated cardiomyopathy or congestive heart failure. Echocardiography and determination of PRA were able to detect early cardiac alterations during the development of dilated cardiomyopathy, despite apparently differing degrees of sensitivity to development of doxorubicin-induced cardiotoxicosis.

Indução da cardiomiopatia dilatada com Doxorrubicina em modelo experimental com coelhos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Mecanismos envolvidos na cardiotoxidade aguda induzida pela doxorrubicina em ratos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Remodelamento do miocárdio na cardiomiopatia dilatada induzida com doxorrubicina em coelhos

Pós-graduação em Medicina Veterinária - FCAV

Efeitos de diferentes frações inspiradas de oxigênio sobre variáveis cardiorrespiratórias e histopatologia pulmonar em coelhos com cardiomiopatia dilatada, anestesiados com sevofluorano

Pós-graduação em Cirurgia Veterinária - FCAV