Abstract Objective The authors design an animal model of neonatal sepsis to analyze the treatment of neonatal septic shock with Methylene Blue (MB) in a swine model. Methods The study design included twenty male newborn pigs divided into four groups: 1) The control group; 2) The sepsis group (induced with lipopolysaccharide); 3) The MB group, and 4) The MB-treated sepsis group. Septic shock was defined as Blood Pressure (BP) dropping 20% below the baseline value. Continuous Blood Pressure (BP), Nitric Oxide (NO) levels, cyclic Guanosine Monophosphate (cGMP), malondialdehyde acid, base excess, lactate, arterial blood gases, hematocrit, and echocardiography were analyzed. Results The BP of the sepsis group treated with MB showed a slight improvement in the first hour after treatment; however, a significant difference was not observed compared to the untreated sepsis group. Besides hemodynamic stability, the current study did not show symptomatic pulmonary hypertension, suggesting that MB was safe in neonates and children. An improvement in Base Excel (BE) levels after MB administration in septic animals may indicate a possible improvement in microcirculation. Conclusion The MB improved biomarkers related to septic shock prognosis, although an improvement in the blood levels could not be detected. MB might be a beneficial drug for hemodynamic instability in infants.

Abstract Atrial septal aneurysm (ASA) is an uncommon but well-recognized cardiac abnormality. This educational text reviews the case of a 54-year-old female presenting an ASA related to a small ostium secundum atrial septal defect. The considerable signs and symptoms, interestingly, have not been justified by the clinical and hemodynamic investigations. So, we opted for a better imaging investigation with cardiac catheterization and transesophageal echocardiography. The surgical process was earlier indicated and performed with aid of cardiopulmonary bypass.

Resumo Fundamento: Diversos estudos têm mostrado que as classes de diterpenos exercem efeito significativo no sistema cardiovascular. Os diterpenos, em particular, estão entre os principais compostos associados às propriedades cardiovasculares, como a propriedade vasorrelaxante, inotrópica, diurética e a atividade hipotensora. Embora o mecanismo de vasorrelaxamento do manool seja visível, seu efeito sobre a pressão arterial (PA) ainda é desconhecido. Objetivo: Avaliar o efeito hipotensor in vivo do manool e verificar o efeito de vasorrelaxamento ex vivo em anéis aórticos de ratos. Métodos: Os animais foram divididos aleatoriamente em dois grupos: normotensos e hipertensos. O grupo normotenso foi submetido à cirurgia sham e adotou-se o modelo 2R1C para o grupo hipertenso. Realizou-se monitoramento invasivo da PA para testes com manool em diferentes doses (10, 20 e 40 mg/kg). Foram obtidas curvas de concentração-resposta para o manool nos anéis aórticos, com endotélio pré-contraído com fenilefrina (Phe) após incubação com Nω-nitro-L-arginina metil éster (L-NAME) ou oxadiazolo[4,3-a]quinoxalina-1-ona (ODQ). Os níveis plasmáticos de óxido nítrico (NOx) foram medidos por ensaio de quimioluminescência. Resultados: Após a administração de manool, a PA se reduziu nos grupos normotenso e hipertenso, e esse efeito foi inibido pelo L-NAME em animais hipertensos apenas na dose de 10 mg/kg. O manool ex vivo promoveu vasorrelaxamento, inibido pela incubação de L-NAME e ODQ ou remoção do endotélio. Os níveis plasmáticos de NOx aumentaram no grupo hipertenso após a administração de manool. O manool induz o relaxamento vascular dependente do endotélio na aorta de ratos, mediado pela via de sinalização NO/cGMP e redução da PA, e também pelo aumento plasmático de NOx. Esses efeitos combinados podem estar envolvidos na modulação da resistência periférica, contribuindo para o efeito anti-hipertensivo do diterpeno. Conclusão: Esses efeitos em conjunto podem estar envolvidos na modulação da resistência periférica, contribuindo para o efeito anti-hipertensivo do diterpeno.

Abstract Background: Many studies have shown that the diterpenoid classes exert a significant effect on the cardiovascular system. Diterpenes, in particular, are among the main compound links to cardiovascular properties such as vasorelaxant, inotropic, diuretic and hypotensive activity. While the manool vasorelaxation mechanism is visible, its effect on blood pressure (BP) is still unknown. Objective: To evaluate the in vivo hypotensive effect of manool and check the ex vivo vasorelaxation effect in rat aortic rings. Methods: The animals were divided randomly into two groups: normotensive and hypertensive. The normotensive group was sham-operated, and the 2K1C model was adopted for the hypertensive group. Invasive BP monitoring was performed for manool tests at different doses (10, 20 and 40 mg/kg). Concentration-response curves for manool were obtained in the aorta rings, with endothelium, pre-contracted with phenylephrine (Phe) after incubation with Nω-nitro-L-arginine methyl ester(L-NAME) or oxadiazole [4,3-a]quinoxalin-1-one (ODQ). Nitric oxide (NOx) plasma levels were measured by chemiluminescence assay. Results: After manool administration, BP was reduced in normotensive and hypertensive groups, and this effect was inhibited by L-NAME in hypertensive animals only in 10 mg/kg dose. Ex vivo manool promoted vasorelaxation, which was inhibited by L-NAME and ODQ incubation or endothelium removal. NOx plasma levels increased in the hypertensive group after manool administration. Manool elicits endothelium-dependent vascular relaxation in rat aorta mediated by the NO/cGMP signaling pathway and BP reduction, also by NOx plasma increase. These combined effects could be involved in modulating peripheral resistance, contributing to the antihypertensive effect of diterpene. Conclusion: These effects together could be involved in modulating peripheral resistance, contributing to the antihypertensive effect of diterpene.

Resumo Fundamento: Geralmente vista como uma característica da velhice, a fragilidade também pode ocorrer em pessoas não idosas, principalmente naquelas que sofrem de doenças crônicas. A fragilidade pode aumentar o risco operatório. Objetivos: Determinar a prevalência de fragilidade em pacientes submetidos à cirurgia de revascularização do miocárdio (CRM) e/ou troca ou reconstrução valvar e/ou cirurgia valvar, bem como a influência da fragilidade nos desfechos pós-operatórios. Métodos: Nosso estudo incluiu 100 adultos que foram submetidos a operações cardíacas eletivas consecutivas. A fragilidade foi avaliada por meio da escala de Fried. Os pacientes também realizaram um teste de caminhada de 6 minutos, e medimos as pressões inspiratória e expiratória máximas. Um valor de p < 0,05 foi considerado significativo. Resultados: De uma coorte de 100 pacientes, com base nos critérios de fragilidade de Fried, 17 pacientes (17%) foram considerados frágeis, 70 (70%) pré-frágeis e apenas 13 (13%) não frágeis. Entre os portadores de valvopatia, 11 (18,6%) foram considerados frágeis e 43 (73%) pré-frágeis. Cinquenta e três por cento dos pacientes considerados frágeis tinham menos de 60 anos (mediana=48 anos). As diferenças no fenótipo de fragilidade entre os pacientes com valvopatia e doença arterial coronariana não foram estatisticamente significativas (p=0,305). A comparação entre pacientes não frágeis, pré-frágeis e frágeis não mostrou diferença significativa na distribuição das comorbidades e do estado funcional cardíaco, independentemente da doença cardíaca. No entanto, a mortalidade hospitalar mostrou-se significativamente maior em pacientes frágeis (29,4%, p=0,026) que em pacientes pré-frágeis (8,6%) e não frágeis (0%). Conclusões: A fragilidade é prevalente mesmo entre pacientes não idosos submetidos a CRM ou cirurgia cardíaca valvar e está associada a maior mortalidade hospitalar pós-operatória.

Abstract Background: Usually viewed as a characteristic of old age, frailty may also occur in non-elderly people, primarily in those suffering from chronic disease. Frailty may increase operative risk. Objectives: To determine the prevalence of frailty patients undergoing coronary artery bypass (CABG) and/or heart valve replacement or reconstruction and/or heart valve surgery, as well as the influence of frailty on postoperative outcomes. Methods: Our study comprised 100 adults who underwent consecutive elective cardiac operations. Frailty was assessed using the Fried scale. Patients also performed a 6-minute walk test, and we measured maximal inspiratory and expiratory pressures. A p value <0.05 was considered significant. Results: Of a cohort of 100 patients, based on the Fried frailty criteria, 17 patients (17%) were considered frail, 70 (70%) pre-frail and only 13 (13%) were non-frail. Among patients with valvular heart disease, 11 (18.6%) were considered frail and 43 (73%) pre-frail. Fifty three percent of the patients considered frail were less than 60 years old (median=48 years old). The differences in frailty phenotype between patients with valvular heart disease and coronary artery disease were not statistically significant (p=0.305). A comparison between non-frail, pre-frail, and frail patients showed no significant difference in the distribution of comorbidities and cardiac functional status, regardless of their cardiac disease. However, hospital mortality was significantly higher in frail patients (29.4%, p=0.026) than in pre-frail patients (8.6%) and non-frail patients (0%). Conclusions: Frailty is prevalent even among non-elderly patients undergoing CABG or valvular heart surgery and is associated with higher postoperative hospital mortality.

Abstract Introduction: Adrenocortical and renal cell carcinomas rarely invade the right atrium (RA). These neoplasms need surgical treatment, are very aggressive and have poor prognostic and surgical outcomes. Case series: We present a retrospective cohort of nine cases of RA invasion through the inferior vena cava (four adrenocortical carcinomas and five renal cell carcinomas). Over 13 years (2002-2014), nine patients were operated in collaboration with the team of urologists. Surgery was possible in all patients with different degrees of technical difficulty. All patients were operated considering the imaging examinations with the aid of CPB. In all reported cases (renal or suprarenal), the decision to use CPB with deep hypothermic circulatory arrest (DHCA) on surgical strategy was decided by the team of urological and cardiac surgeons. Conclusion: Data retrospectively collected from patients of public hospitals reaffirm: 1) Low incidence with small published series; 2) The selected cases did not represent the whole historical casuistry of the hospital, since they were selected after the adoption of electronic documentation; 3) Demographic data and references reported in the literature were presented as tables to avoid wordiness; 4) The series highlights the propensity to invade the venous system; 5) Possible surgical treatment with the aid of CPB in collaboration with the urology team; 6) CPB with DHCA is a safe and reliable option; 7) Poor prognosis with disappointing late results, even considering the adverse effects of CPB on cancer prognosis are expected but not confirmed.

Abstract It is well known that during hepatic operative procedures, it is often critical that the irrigation is interrupted to avoid possible bleeding, blood transfusions, variable intensities, and their short and long-term consequences. It was believed in the past that the flow interruption should not exceed 20 minutes, which limited the use of this maneuver. However, it has been postulated that ischemia could be maintained for more than 60 minutes in healthy livers. The present paper review includes: 1) A brief introduction to justify the rationale of the review design; 2) Aspects of the pathophysiology of the three stages of the liver ischemia-reperfusion injury; 3) The innate and acquired immunity; 4) Oxidative stress; 5) Apoptosis and autophagy, Some essential biomarkers (Tumor Necrosis Factor-α, nitric oxide, metalloproteinases); and, finally; 6) Preventive (“cheating”) strategies, non-pharmacological and pharmacological options to treat the liver IR injury.

Abstract Nonvalvular atrial fibrillation is associated with a 4- to 5-fold strokes increase and may be responsible for 15% to 20% of all strokes in the elderly. In this scenario, the left atrial appendage thrombus would be the associated with 90% of cases. The use of anticoagulants, percutaneous devices, and the left atrial appendage surgical exclusion is still an open discussion. For left atrial appendage procedures, relevant anatomic spatial relationships have to be emphasized, besides the chance of the normal physiological functioning would be eliminated with the proceedings. There are evidences that the left atrial appendage closure during routine cardiac surgery is significantly associated with an increased risk of early postoperative atrial fibrillation. Therefore, the purpose of this review is to focus basic aspects for continuous medical education. In summary, the rationale of this text is to emphasize anatomical and pharmacological aspects involved in the simple surgical exclusion of left atrial appendage under cardiopulmonary bypass. There are several operative techniques, but to conclude this revision it will present one of them based on the discussed basic sciences.

Resumo Fundamento: O diterpeno Esclareol tem ação antimicrobiana, efeitos citotóxicos e citostáticos e atividades antitumorais. No entanto, pesquisas sobre o sistema cardiovascular são escassas. Objetivo: Este estudo foi desenvolvido para investigar os mecanismos envolvidos no efeito cardiovascular de Esclareol em ratos normotensos e hipertensos. Métodos: A hipertensão arterial foi promovida utilizando modelo de 2 clones de 1-clipe em ratos. O efeito do esclareol sobre a pressão arterial foi realizado utilizando três doses (10, 20 e 40 mg/kg). As curvas dose-resposta cumulativas para Esclareol foram determinadas para anéis aórticos endotélio-intactos e desprovidos de endotélio na presença ou ausência de L-NAME e ODQ. Os níveis de NOx foram medidos na amostra de plasma. Resultados: A administração de Esclareol in vivo causou uma redução significativa na pressão sanguínea em ambos os grupos. In vitro o esclareol promoveu relaxamento na aorta, com endotélio, pré-contraído a Phe. Os inibidores da óxido nítrico sintase e da guanilato ciclase solúvel foram tão eficientes quanto a remoção do endotélio, na inibição do relaxamento induzido por Esclareol. Por outra parte, não houve mudança de NOx. Além disso, por razões desconhecidas, o Sclareol não é seletivo para animais hipertensos. Conclusão: O diterpeno Esclareol apresentou efeitos hipotensores in vivo e vasodilatadores in vitro; A análise de NO plasmático por quimioluminescência não mostrou diferença significativa entre os grupos e O Esclareol exibe melhor efeito sobre os animais normotensos do que hipertensos para reduzir a pressão arterial. Conclui-se que os metabólitos de diterpenos seriam um protótipo de fonte promissora para o desenvolvimento de novos agentes na terapia cardiovascular.

Abstract Background: The diterpene Sclareol has antimicrobial action, cytotoxic and cytostatic effects and anti-tumor activities. However, researches on the cardiovascular system are scarce. Objective: This study was designed to investigate the mechanisms involved in the Sclareol cardiovascular effect in normotensive and hypertensive rats. Methods: The arterial hypertension was promoted using 2-kidneys 1-clip model in rats. The effect of sclareol on blood pressure was performed by using three dose (10, 20 and 40 mg/kg). Cumulative dose-response curves for Sclareol were determined for endothelium-intact and endothelium-denuded aortic rings in presence or absence of L-NAME and ODQ. The NOx levels were measure in the plasma sample. Results: The Sclareol administration in vivo caused a significant reduction in blood pressure in both groups. In vitro the sclareol promoted relaxation in aorta, with endothelium, pre-contracted to Phe. The inhibitors of the nitric oxide synthase and soluble guanylate cyclase were as efficient as the removal of endothelium, in inhibiting the Sclareol-induced relaxation. Otherwise, it was no change of NOx. Also, for unknown reasons, the Sclareol is not selective for hypertensive animals. Conclusion: The diterpene Sclareol showed in vivo hypotensive and in-vitro vasodilator effects; The chemiluminescence plasmatic NO analysis showed no significant difference between groups and The Sclareol exhibit better effect on normotensive than hypertensive animals to reduce blood pressure. It is concluded that the diterpenes metabolites would be a promising source prototype for the development of new agents in the cardiovascular therapy.

Abstract Scientific progress shall ultimately boost the current acceptance level for conservative aortic valve surgery. The present text aimed to report the 23-year long-term follow-up of one patient operated with bovine pericardium cusp extension. Growing confidence in the efficacy of the operation will allow a more expeditious indication for surgical treatment, as is already the case in mitral valve repair. This change of attitude will certainly make it possible for patients to be sent for operation in mild aortic valve regurgitation. The present report reinforces the concept and highlights the impression that the aortic valvoplasty, independent of the progressive bovine pericardium degeneration, may positively change the natural history of the aortic valve insufficiency.

Abstract Objective: In cardiac surgery, the lung, renal and neurological events are the most frequent complications. Less common, acute liver failure is a serious complication that adds high morbidity, mortality, and costs. Therefore, this communication aimed to retrospectively evaluate five patients who presented, in 2014, severe acute liver failure in the immediate postoperative period. Methods: Retrospective data analysis of patients' medical records that showed severe liver failure has been computed in the medical records of five patients undergoing cardiac surgery at the Hospital da Faculdade de Medicina de Ribeirão Preto – USP in the immediate postoperative period from February 1, 2014 to December 12, 2014. The study selected five males patients, 60 to 67 years old, cardiopulmonary bypass mean time of 101.4 minutes (varying from 80 to 140 minutes), who presented acute perioperative liver failure. Results: The five patients showed an impressive increase of blood transaminase (serum alanine aminotransferase), suggesting acute hepatitis. The evolution of all patients was catastrophic, with severe hemodynamic effects and death. Many studies suggest that systemic hypotension is an important pathogenic factor for ischemic hepatitis. However, our data and previous studies raise the possibility that other yet unknown factors other than hypotension may be part of the pathophysiology of cardiopulmonary bypass after ischemic hepatitis (anticoagulation inadequate for the quality of heparin and protamine, etc.). Conclusion: Currently, there are no conclusive studies on the prevention of perioperative liver failure. More well-designed studies are needed on the introduction and evolution of liver dysfunction after cardiac surgery.

Resumo Uma visão geral de estudos angiográficos na literatura mostrou que a prevalência da doença coronária significativa em pacientes com estenose aórtica (EA) varia de 20 a 60%. Os estudos iniciais de necropsia sugeriram que pacientes com EA tinham uma incidência abaixo do esperado de doença arterial coronariana (DAC), assim originando-se o conceito de um efeito protetor da EA nas artérias coronárias. O mito da proteção EA contra a DAC seria melhor explicado como uma interação endotélio-miocárdio (crosstalk) desencadeada pela sobrecarga do ventrículo esquerdo. Portanto, a via cGMP/NO, (guanosina monofosfato cíclico/Óxido nítrico) induzida pela pressão de sobrecarga da EA, explicaria a baixa incidência de DAC, o que é compatível com a surpreendente evolução natural em longo prazo dessa doença valvar cardíaca.

Abstract A literature overview of angiographic studies has shown that the prevalence of significant coronary disease in patients with aortic stenosis (AS) varies from 20 to 60%. Early necropsy studies suggested that patients with AS had a lower than expected incidence of coronary artery disease (CAD), originating the concept of a protective effect of AS on the coronary arteries. The myth of AS protection against CAD would be better explained as endothelium-myocardial interaction (crosstalk) protection triggered by left ventricular overload. Therefore, the cGMP/NO pathway induced by the AS overload pressure would explain the low incidence of CAD, which is compatible with the amazing natural long-term evolution of this cardiac valve disease.

Abstract Ventricular constraint therapy has been used to prevent and reverse the progression of heart failure in ischemic and nonischemic cardiomyopathies. We hypothesized that ventricular restraint should be tried by closing the pericardium that was previously opened following left ventricle topographical projection. The surgical technique presentation is illustrated by a remarkable 13-year outcome of one patient with dilated cardiomyopathy treated surgically by mitral prosthesis, Cox/Maze III surgery to treat atrial fibrillation, and associated to the ventricular constraint using the patient's own pericardium. The ventricular pericardial restraint role is unclear, since the patient had multiple corrections that could be responsible for the good outcome; however it is viable deserving investigations.