Increased Atrial ß-Adrenergic Receptors and GRK-2 Gene Expression Can Play a Fundamental Role in Heart Failure After Repair of Congenital Heart Disease with Cardiopulmonary Bypass.

Surgeries to correct congenital heart diseases are increasing in Brazil and worldwide. However, even with the advances in surgical techniques and perfusion, some cases, especially the more complex ones, can develop heart failure and death. A retrospective study of patients who underwent surgery for correction of congenital heart diseases with cardiopulmonary bypass (CPB) in a university tertiary-care hospital that died, showed infarction in different stages of evolution and scattered microcalcifications in the myocardium, even without coronary obstruction. CPB is a process routinely used during cardiac surgery for congenital heart disease. However, CPB has been related to increased endogenous catecholamines that can lead to major injuries in cardiomyocytes. The mechanisms involved are not completely understood. The aim of this study was to evaluate the alterations induced in the ß-adrenergic receptors and GRK-2 present in atrial cardiomyocytes of infants with congenital heart disease undergoing surgical repair with CPB and correlate the alterations with functional and biochemical markers of ischemia/myocardial injury. The study consisted of right atrial biopsies of infants undergoing surgical correction in HC-FMRPUSP. Thirty-three cases were selected. Atrial biopsies were obtained at the beginning of CPB (group G1) and at the end of CPB (group G2). Real-time PCR, Western blotting, and immunofluorescence analysis were conducted to evaluate the expression of ß1, ß2-adrenergic receptors, and GRK-2 in atrial myocardium. Cardiac function was evaluated by echocardiography and biochemical analysis (N-terminal pro-brain natriuretic peptide (NT-ProBNP), lactate, and cardiac troponin I). We observed an increase in serum lactate, NT-proBNP, and troponin I at the end of CPB indicating tissue hypoxia/ischemia. Even without major clinical consequences in cardiac function, these alterations were followed by a significant increase in gene expression of ß1 and ß2 receptors and GRK-2, suggesting that this is one of the mechanisms responsible for the exacerbated response of cardiomyocytes to circulating catecholamines. These alterations could explain the irreversible myocardial damage and lipid peroxidation of membranes classically attributed to catecholamine excess, observed in some infants who develop heart failure and postoperative death. Although other factors may be involved, this study confirms that CPB acts as a potent inducer of increased gene expression of ß- adrenergic receptors and GRK-2, making the myocardium of these infants more susceptible to the effects of circulating endogenous catecholamines, which may contribute to the development of irreversible myocardial damage and death.

Desmoid Tumor After a Minimally Invasive Atrial Septal Defect Closure in an Adolescent.

The surgical closure of secundum atrial septal defect (ASD) is frequently performed. The minimally invasive approach, currently adopted by many centers as a way to preserve aesthetic appearance, particularly in female patients, seems to be safe. We describe the case of an adolescent who developed a desmoid tumor soon after a minimally invasive operation for surgical closure of a secundum ASD.

Outcomes of Patients After Arterial Switch Operation: 18 Years of Experience in a Single Medium-Volume Center.

The objective of this paper was to describe the outcomes in patients submitted to arterial switch operation and to analyze the predictors of in-hospital mortality and further need of re-operation at a single-center institution. Between September 1995 and January 2014, 128 consecutive arterial switch operations were performed. Surgical mortality during this period was analyzed retrospectively, and a follow-up analysis of the survivors was conducted. Surgical era, cardiopulmonary bypass time (p = 0.001), and diagnosis category (p = 0.025) influenced in-hospital mortality. The estimated overall survival for the 91 hospital survivors was 96.8, 96.4, and 96.2 % at 5, 10, and 15 years, respectively. The median follow-up time was 67 months (range 0.71-222 months). Three patients (5 %) presented severe aortic regurgitation. Right ventricle outflow tract systolic gradient by echocardiography was above 60 mmHg in 2 %. Late re-interventions occurred in 12 (13 %) patients with mean time of 64 ± 34 months after the initial procedure. Actuarial freedom from re-interventions at 5, 10, and 15 years was 96.4, 69.7, and 61.9 %, respectively. Arterial switch operation remains the procedure of choice in patients with transposition of great arteries. It can be performed even in middle-volume institutions, leading to the same middle- and long-term outcomes of high-volume institutions. Early high mortality rate may occur due not only to learning curve, but also to cardiopulmonary bypass time and ventricular septal defect closure.

Ischemic myocardial injuries after cardiac malformation repair in infants may be associated with oxidative stress mechanisms.

BACKGROUND: Despite advances in pediatric cardiac surgery, perioperative myocardial injury can be the major determinant of postoperative dysfunction after cardiac surgery. This study investigated the pathology-related differences in 29 infants with congenital heart disease that led to death. The infants were treated at the University Hospital of Ribeirão Preto, Brazil. METHODS: The patients were divided into four groups: Group 1, 16 infants who underwent operations for congenital heart disease on cardiopulmonary bypass; Group 2, four infants who underwent off-cardiopulmonary bypass operations for congenital heart disease; Group 3, nine infants who died from congenital heart disease prior to surgical treatment; and Group 4 (control group), five infants with no congenital heart disease and who died from other causes. The myocardial injuries and oxidative stress mechanisms were assessed by histopathology and immunohistochemistry and were quantified by morphometrical analyses. RESULTS: Contraction band necrosis and dystrophic calcification were found primarily in infants of Group 1. Coagulation necrosis and healing were prominent in Group 2, while infants without repair (Group 3) showed mainly colliquative myocytolysis. Apoptotic cells were more prominent in the operative groups. The control group showed no significant myocardial lesions. Lipid peroxidation was the principal mechanism of oxidative stress accounting for the myocardial lesions. CONCLUSION: The diversity of the lesions observed in these hearts seemed to indicate a large spectrum of cell damage due to inadequate myocardial perfusion, especially when these infants underwent surgery. Oxidative mechanisms could be a common mediator in the pathogenesis of myocardial injuries, mediated by peroxidation of the membrane phospholipids and resulting in changes in the permeability of the cell membrane, cell death, and intracellular calcium overload. Furthermore, an immature and often hypertrophied myocardium may promote unfavorable conditions, leading to heart failure and a lethal outcome.

Blood cardioplegia with N-acetylcysteine may reduce coronary endothelial activation and myocardial oxidative stress.

OBJECTIVES: The aim of this prospective study was to compare the efficacy of intermittent antegrade blood cardioplegia with or without n-acetylcysteine (NAC) in reducing myocardial oxidative stress and coronary endothelial activation. METHODS: Twenty patients undergoing elective isolated coronary artery bypass graft surgery were randomly assigned to receive intermittent antegrade blood cardioplegia (32 degrees C-34 degrees C) with (NAC group) or without (control group) 300 mg of NAC. For these 2 groups we compared clinical outcome, hemodynamic evolution, systemic plasmatic levels of troponin I, and plasma concentrations of malondialdehyde (MDA) and soluble vascular adhesion molecule 1 (sVCAM-1) from coronary sinus blood samples. RESULTS: Patient demographic characteristics and operative and postoperative data findings in both groups were similar. There was no hospital mortality. Comparing the plasma levels of MDA 10 min after the aortic cross-clamping and of sVCAM-1 30 min after the aortic cross-clamping period with the levels obtained before the aortic clamping period, we observed increases of both markers, but the increase was significant only in the control group (P= .039 and P= .064 for MDA; P= .004 and P= .064 for sVCAM-1). In both groups there was a significant increase of the systemic serum levels of troponin I compared with the levels observed before cardiopulmonary bypass (P< .001), but the differences between the groups were not significant (P= .570). CONCLUSIONS: Our investigation showed that NAC as an additive to blood cardioplegia in patients undergoing on-pump coronary artery bypass graft surgery may reduce oxidative stress and the resultant coronary endothelial activation.

Risk stratification in neonates and infants submitted to cardiac surgery with cardiopulmonary bypass: a multimarker approach combining inflammatory mediators, N-terminal pro-B-type natriuretic peptide and troponin I.

Low cardiac output syndrome (LCOS) is a common problem following cardiac surgery with cardiopulmonary bypass (CPB) in neonates and infants, and its early recognition remains a challenging task. We aimed to test whether a multimarker approach combining inflammatory and cardiac markers provides complementary information for prediction of LCOS and death in children submitted to cardiac surgery with CPB. Forty-six children younger than 18 months with congenital heart defects were prospectively enrolled. No intervention was made. Blood samples were collected pre-operatively, during CPB and post-operatively (PO) for measurement of interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor (TNF)-alpha, cardiac troponin I (cTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Clinical data and outcome variables were recorded. Logistic regression was used to identify predictors of LCOS and death. Multivariate logistic regression identified pre-operative NT-proBNP and IL-8 4h PO as independent predictors of LCOS, while cTnI 4h PO and CPB length were independent predictors of death. The use of inflammatory and cardiac markers in combination improved sensitivity, negative predictive value and accuracy of the models. In conclusion, the combined assessment of inflammatory and cardiac biochemical markers can be useful for identifying young children at increased risk for LCOS and death after heart surgery with CPB.

Extrinsic compression of left main coronary artery from aneurysmal dilation of pulmonary trunk in a adolescent: involution after surgery occlusion of sinus venosus atrial septal defect and pulmonary trunk plasty for reduction.

We report the case of an adolescent referred with initial diagnosis of pulmonary hypertension. Non-invasive investigation disclosed a sinus venous atrial septal defect with pulmonary hypertension. The hemodynamic study confirmed diagnosis, and also showed extrinsic compression of left main coronary artery by pulmonary trunk. Surgical closure of the defect in addition to pulmonary trunk plasty were undertaken. Two years after the surgery the patient is well, with clinical signs of mild pulmonary hypertension, and showing no evidence--also on echocardiogram--of left coronary artery trunk obstruction.

Compressão extrínseca da artéria coronária esquerda por dilatação aneurismática do tronco pulmonar em adolescente: involução após oclusão cirúrgica de comunicação interatrial seio venoso e plastia redutora do tronco pulmonar / Extrinsic compression of left main coronary artery from aneurysmal dilation of pulmonary trunk in a adolescent: involution after surgery occlusion of sinus venosus atrial septal defect and pulmonary trunk plasty for reduction

Relatamos o caso de um adolescente encaminhado com o diagnóstico de hipertensão pulmonar. A investigação não invasiva detectou comunicação interatrial seio venoso com sinais de hipertensão pulmonar. No estudo hemodinâmico o diagnóstico foi confirmado, sendo também notada compressão esquerda pelo tronco pulmonar. O paciente foi submetido à oclusão cirúrgica da comunicação interatrial e à plastia redutora do tronco pulmonar. Dois anos após o procedimento, o paciente encontra-se bem, com sinais clínicos e ecocardiográficos de hipertensão pulmonar discreta e sem evidências, também pelo ecocardiograma, de obstrução do tronco da artéria coronária esquerda.

We report the case of an adolescent referred with initial diagnosis of pulmonary hypertension. Non-invasive investigation disclosed a sinus venous atrial septal defect with pulmonary hypertension. The hemodynamic study confirmed diagnosis, and also showed extrinsic compression of left main coronary artery by pulmonary trunk. Surgical closure of the defect in addition to pulmonary trunk plasty were undertaken. Two years after the surgery the patient is well, with clinical signs of mild pulmonary hypertension, and showing no evidence - also on echocardiogram - of left coronary artery trunk obstruction.

Anomalous origin of the left coronary artery from the pulmonary artery in an adult with systemic collateral circulation to the left coronary artery.

A case of anomalous origin of the left coronary artery from the pulmonary artery in an adult with collateral circulation between the left coronary artery and systemic extracardiac vessels is reported. After evaluating the surgical options, my colleagues and I conclude that ligation of the left coronary artery and a left internal thoracic artery graft to the left anterior descending coronary artery is the preferable option for treating such patients.

Dorsal minithoracotomy for ductus arteriosus clip closure in premature neonates.

We present a new surgical technique for patent ductus arteriosus (PDA) occlusion in premature neonates (PN). Through a dorsal minithoracotomy the PDA is dissected extrapleurally with q-tips and clipped. The short surgical time, avoidance of pleural drainage, and prevention of late breast deformity are the operation highlights.

Coronary sinus iatrogenic lesion during repeated mitral valve replacement: case report of an immediate transmitral annulus repair

Apresenta-se a história e a evoluçäo de uma paciente no qual o seio coronariano foi lesado e, imediatamente, reconstruído através do anel valvar mitral. O acidente cirúrgico aconteceu durante a instrumentaçäo para remoçäo de uma prótese biológica degenerada. Uma quase completa lesäo da artéria coronária circunflexa foi a primeira impressäo. Um calibrador coronariano foi distalmente detectado dentro do átrio direito, mostrando tratar-se de uma lesäo do seio coronariano. A correçäo cirúrgica foi realizada por sutura contínua com fio de polipropileno 7-0 através do anel valvar. Uma angiografia, realizada após 14 meses, mostrou apenas discreto estreitamento do seio coronariano no local da sutura, observando-se a fase venosa de uma arteriografia seletiva da artéria coronária descendente anterior. Os autores acreditam que a simples ligadura ou a reconstruçäo do seio coronariano, na condiçäo iatrogênica apresentada, é motivo para especulações.

Origem anômola da artéria pulmonar esquerda da aorta. Correçäo cirúrgica bem sucedida em lactente com tetralogia de Fallot / Anomalous origin of the left pulmonary artery from the ascending aorta. Successful surgical correction in an infant with Fallot's tetralogy

We describe the case of a 40-day-old female patient with a history of breathlessness since birth who was referred to our hospital for surgical correction of common arterial trunk. The invasive investigation disclosed a Fallotós tetralogy anatomy associated with an anomalous origin of the left pulmonary artery from the ascending aorta. Immediately after diagnosis, the patient underwent a successful total surgical correction of the defect, including simultaneous anastomosis of the left pulmonary artery to the pulmonary trunk

Vasoplegia em cirurgia cardíaca: fisiopatologia, diagnóstico e conduta / Vasoplegia following cardiac surgery: physiopathology, diagnostic and management

A vasoplegia é uma antiga causa de instabilidade hemodinâmica em cirurgia cardíaca. Estatísticas baseadas em estratificação de riscos utilizando marcadores da inflamação evidenciam incidência precoce de 2 por cento a 10 por cento associada a maior morbidade e a maior mortalidade. Nesta revisão são discutidos os aspectos fisiopatológicos, enfatizando a reação inflamatória sistêmica, os efeitos da protamina e o comprometimento dos receptores da vasopressina. Além dos aspectos fisiopatológicos, ressaltam-se os aspectos diagnósticos e terapêuticos. Os conceitos adotados para a revisão são embasados em conhecimentos laboratoriais e clínicos sobre a função endotelial. Os autores destacam suas condutas pessoais, suas dúvidas e perspectivas futuras, com especial ênfase no tratamento farmacológico da vasoplegia com a utilização endovenosa do azul de metileno.

Implante subvalvar do anel da prótese no tratamento cirúrgico dos aneurismas da aorta ascendente / Subvalvar implantation of the prosthesis sewing ring in the surgical treatment of ascending aorta aneurysms

Descreve-se modificaçäo técnica da operaçäo de Bentall e DeBono, para substituiçäo completa da aorta ascendente e valva aórtica. Consiste na passagem de pontos separados em U, sucessivamente, no anel de fixaçäo da prótese e no anel da valva aórtica. A posiçäo subvalvar do anel protético, assim obtida, facilita o reimplante dos óstios coronários, sobretudo quando se encontram pouco deslocados, distalmente, como nos pequenos aneurismas. Além disso, a anastomose proximal tubo-aórtica, resulta mais segura. Quinze pacientes portadores de aneurisma da aorta ascendente foram operados por essa técnica: 14 com próteses separadas e 1 com tubo valvado. Com uma exceçäo, nos demais foi possível fazer o reimplante direto dos óstios coronários na prótese tubular. Ocorreram 2 óbitos hospitalares näo relacionados à técnica. Os outros 13 pacientes foram seguidos por períodos variáveis de 72 dias a 109 meses, näo se constatando qualquer disfunçäo da prótese valvar em avaliaçöes clínicas e ecocardiográficas. Destes, 2 faleceram após 6 e 40 meses, de causa ignorada e dissecçäo de aneurisma toracoabdominal, respectivamente.

Cardioplegia sangüínea normotérmica intermitente anterógrada: estudo experimental em coelhos / Intermittent anterograde normothermic blood cardioplegia: experimental study in rabbits

Objetivos: Investigar a proteçäo miocárdica proporcionda pela infusäo anterógrada intermitente, durante 60 minutos, de soluçäo cardioplégica sangüínea a 37 graus Celsius, em coraçöes normais isolados de coelhos. Material e Métodos: Foram estudados 32 coelhos da raça Nova Zelândia, divididos em grupos, Experimental e Controle. O estudo foi realizado em 2 fases: Fase I: Estudo metabólico após isquemia sem reperfusäo. Fase II: Estudo metabólico e funcional após reperfusäo. A reperfusäo foi realizada utilizando-se um sistema de perfusäo parabiótica. Determinou-se o glicogênio miocárdico e a respiraçäo mitocondrial no miocárdio ventricular imediatamente ao final do período de infusäo intermitente da soluçäo cardioplégica (Fase I) e após reperfusäo sangüínea (Fase II), durante a qual analisou-se, também, a funçäo ventricular esquerda (dP/dtmax). Resultados: Detectou-se queda significativa nos níveis de glicogênio miocárdico de 58 por cento em relaçäo ao controle, ao final do período de infusäo (Fase I). Na fase com reperfusäo (Fase II), as diferenças no glicogênio miocárdico entre o grupo experimental e seu controle näo foram significativas. A análise da respiraçäo mitocondrial näo mostrou diferenças significativas entre os grupos experimentais e seus controles, quer seja nas fases com ou sem reperfusäo. Os valores da dP/dtmax; na Fase II foram de 903,39 + 113,46 mmHg/s e 1.043 + 256,94 mmHg/s, para o grupo experimental e controle, respectivamente. A diferença entre os valores nao foi significativa. Conclusöes: A infusao anterógrada intermitente a cada 20 minutos, durante 60 minutos, de soluçäo cardioplégica sangüínea a 37 graus Celsius, mostrou-se um método eficaz de proteçäo miocárdica em coraçöes normais de coelhos.

Contratura isquêmica do miocárdio: estudo experimental em ratos / Ischemic contracture of the myocardium: experimental study in rats

A contratura isquêmica do miocárdio (CIM) tem sido muito utilizada na investigaçäo da fisiopatologia da isquemia global do coraçäo. Este trabalho descreve um modelo experimental adequado ao estudo da CIM, em ratos. Foram empregados 8 animais da raça Wistar, anestesiados com éter sulfúrico. O coraçäo, removido rapidamente por toracotomia, foi imerso em soluçäo de NaCl 0,9 por cento a 37 Graus Celsius. Por meio de um cateter-balao de látex introduzido na cavidade ventricular esquerda, insuflado sob pressäo de 20 mmHg e conectado a um eletrofisiógrafo, registrou-se o início da CIM (TCI) e sua intensidade (IC). A dP/dT do fenômeno foi calculada. Definiu-se uma elevaçäo de 5 mmHg na linha de base do traçado como indicativa do início da contratura. O ponto de inflexäo da curva representou a intensidade da contratura (IC). A dP/dT foi calculada. Os resultados (média + desvio padräo) obtidos foram semelhantes aos da literatura: TCI (min) = 15,5 + 0,59; IC (mmHg) = 62,0 + 5,81; dP/dT (mmHg/min) = 14,2 + 3,05.

Fluxo coronário desregulado durante reperfusäo pós cardioplegia / Coronary flow response is impaired during post-cardioplegia

Estudaram-se a demanda metabólica e a distribuiçäo do fluxo coronariano na presneça de fibrilaçäo ventricular (FV), durante a reperfusäo pós-cardioplegia. Foram colocados 15 suínos em circulaçäo extracorpórea e submetidos a parada cardíaca cardioplégica sangüínea anterógrada hipotérmica intermitente, durante uma hora, seguida por reperfusäo miocárdica controlada. Os animais foram divididos em três grupos (n=5), conforme estivessem em assistolia (Grupo 1) ou em FV de curta (grupo 2) ou longa duraçäo (Grupo 3), durante os dez primeiros minutos de reperfusäo. Os valores do consumo miocárdico de oxigênio (MVO2), em ml O2/min/g (média + erro padräo) durante a reperfusäo foram de 1,325 + 0,144 (grupo 1); 2,472 + 0,208 (Grupo 2) e 2,469 + 0,228 (Grupo 3). A diferença entre o MVO2 dos coraçöes em assistolia e o dos coraçöes em FV, quer de curta ou longa duraçäo, foi significante (p<0,001). A relaçäo entre os fluxos sangüíneos endo e epicárdico, bem como o fluxo sangüíneo coronário global (ml/mim/100g) foram semelhantes nos 3 grupos. Os valores dessa última variável, em ml/mim/100g, corresponderam a, respectivamente, 169,3 + 11,7; 185,0 + 15,7 e 179,9 + 13,2. Os resultados demonstram que a auto-regulaçäo coronária está alterada durante a fase inicial de reperfusäo pós criocardioplegia, pois a perfusäo miocárdica näo aumentou em resposta à elevaçäo do consumo de oxigênio imposta pela FV. Essa constataçäo, de grande interesse clínico, sugere que a ocorrência de FV durante a fase inicial da reperfusäo possa contribuir para o desenvolvimento de lesöes teciduais em coraçöes cujo fluxo coronário já esteja previamente comprometido, por obstruçäo coronária, distensäo ou hipertrofia ventricular.