Pretreatment with P2Y12 inhibitors in ST-elevation myocardial infarction: A systematic review and meta-analysis.

BACKGROUND: Pretreatment with oral P2Y12 inhibitors is a standard practice for ST-elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI). However, the efficacy and safety of P2Y12 inhibitors pretreatment remain unclear. OBJECTIVES: We conducted a meta-analysis to investigate the impact of P2Y12 inhibitor pretreatment on thrombotic and hemorrhagic endpoints in STEMI patients. METHODS: We searched multiple databases for studies that compared P2Y12 inhibitor pretreatment with no pretreatment in STEMI patients and reported endpoints of interest. Random effects model was used for the meta-analysis. RESULTS: Our meta-analysis included 3 randomized controlled trials and 14 observational studies, comprising 70,465 patients assigned to either P2Y12 inhibitor pretreatment (50,328 patients) or no pretreatment (20,137 patients). Compared to no pretreatment, P2Y12 inhibitor pretreatment did not result in significant reductions in all-cause mortality (risk ratio [RR] 0.73; 95% confidence interval [CI]: 0.52-1.03; p = 0.07), myocardial infarction (RR 0.75; 95% CI: 0.53-1.07; p = 0.11), or major bleeding (RR 0.80; 95% CI: 0.56-1.16; p = 0.22) at 30 days. However, our subgroup analysis revealed that P2Y12 inhibitor pretreatment administered in the pre-hospital setting was associated with a significant reduction in the incidence of myocardial infarction compared to no pretreatment (RR 0.73; 95% CI: 0.56-0.91; p < 0.01). CONCLUSION: Our analysis suggests that pretreatment with oral P2Y12 inhibitors before PCI in patients with STEMI was not associated with reduced all-cause mortality, myocardial infarction, or major bleeding. However, pretreatment with P2Y12 inhibitors in the pre-hospital setting appears to be beneficial in reducing reinfarction.

Prevalência de regurgitação paravalvar após implante transcateter de válvula aórtica / Prevalence of paravalve regurgitation after aortic valve transcatheter implantation

Introdução: Com o envelhecimento populacional brasileiro, esperase que a incidência de doenças cardiovasculares, como a estenose e insuficiência da válvula aórtica, eleve-se. Desde 2002, o implante valvar aórtico transcateter demonstrou-se método de alta eficácia no seu tratamento. No entanto, o procedimento está sujeito ao regurgitamento paravalvar. Objetivo: Avaliar quantitativamente a prevalência dessa regurgitação em pacientes submetidos ao Implante valvar aórtico transcateter. Métodos: Estudo observacional, transversal, retrospectivo que analisou 38 casos de Implante valvar aórtico transcateter. Os dados foram coletados dos prontuários, que incluíram informações antropométricas, comorbidades e procedimentos prévios à operação, e analisou-se a presença de refluxo paravalvar no 1° mês e 1° ano pós-Implante valvar aórtico transcateter. Resultados: A idade média foi de 74 ±11,2 anos; 15 pacientes dos analisados, possuíam classificação NYHA igual a III, e 1 NYHA IV, previamente à operação. Do total, 36,32% (n=8) tinham refluxo paravalvar no 1° mês e 1º. ano após o procedimento cirúrgico. Conclusão: A prevalência de refluxo paravalvar pós-operatório em pacientes submetidos ao Implante valvar aórtico transcateter, foi igual a 36,3% tanto para a avaliação realizada no 1° mês quanto no 1° ano.

Introduction: With the aging of the Brazilian population, it is expected that the incidence of cardiovascular diseases, such as stenosis and insufficiency of the aortic valve, will increase. Since 2002, transcatheter aortic valve implantation has proved to be a highly effective method of treatment. However, the procedure is subject to paravalvular regurgitation. Objective: To quantitatively assess the prevalence of paravalvular regurgitation in patients undergoing Transcatheter aortic valve implantation. Methods: Observational, cross-sectional, retrospective study that analyzed 38 Transcatheter aortic valve implantation cases. Data were collected from medical records, which included anthropometric information, comorbidities and procedures prior to the operation, and the presence of paravalvular regurgitation in the 1st month and 1st year after Transcatheter aortic valve implantation was analyzed. Results: Mean age was 74 ±11.2 years; 15 of the analyzed patients had NYHA classification equal to III, and 1 NYHA IV, prior to the operation. Of the total, 36.32% (n=8) of the patients had paravalvular regurgitation in the 1st and 1st month. year after the surgical procedure. Conclusion: The prevalence of postoperative paravalvular regurgitation in patients undergoing Transcatheter aortic valve implantation was equal to 36.3% both for the assessment carried out in the 1st month and in the 1st year

EVALUATION OF THE OMENTUM AS A STEM CELL DONOR ISCHEMIC MYOCARDIAL THROUGH CD34 IMMUNOHISTOCHEMICAL ANALYSIS / AVALIAÇÃO DO OMENTO COMO DOADOR DE CÉLULAS TRONCO NO MIOCÁRDIO ISQUÊMICO ATRAVÉS DA ANÁLISE IMUNOHISTOQUÍMICA DO CD34

Background: Cardiovascular diseases are the leading cause of death in the world. The use of hematopoietic precursor cells and recent advances made in heart graft bioengineering offer a new therapeutic modality for post-myocardial infarction (MI)  and cardiac tissue regeneration. CD34 is a marker expressed on all hematopoietic and endothelial precursor cells, and functions as a cell adhesion factor. The antibody corresponding to this marker is used in immunohistochemistry to assess the formation of new vessels and the presence of stem cells. Aim: To evaluate the efficacy of omentopexy as stem cell donor, on previously infarcted myocardium, using immunohistochemically analysis of CD34. Method: Myocardial infarction was generated in four pigs, by ligature of the 1st and 2nd marginal branches of the circumflex artery. In three animals, abrasion of the infarcted epicardium was performed followed by multiple myocardial perforations and the mobilization of the omentum from the abdominal cavity to the mediastinum, sutured on the infarcted area. In the fourth animal, omentopexy was not performed and only the abrasion and perforation of the infarcted area were performed. All hearts were removed for CD34 immunohistochemically evaluation. Results:  In the samples from the group submitted to omentopexy, there was a 60% increase in angiogenesis, and in the samples from the control animal there was minimal staining.  Four samples from different sites of each animal, totaling 16 histopathological samples were evaluated. All samples were immunolabelled for CD34. Conclusions: Omentopexy proved to be effective in seeding previously infarcted myocardium with stem angiogenic cells, seen through immunohistochemistry, using CD34 marker.

Racional: As doenças cardiovasculares são a principal causa de morte no mundo. O uso de células precursoras hematopoiéticas e os recentes progressos feitos na bioengenharia de enxertos cardíacos oferecem uma nova modalidade terapêutica para a regeneração do tecido cardíaco pós-infarto do miocárdio (IM). O CD34 é um marcador expresso em todas as células precursoras hematopoiéticas e endoteliais, e funciona como fator de adesão celular. O anticorpo que correspondente a este marcador é utilizado na imunohistoquímica para avaliar a formação de novos vasos e a presença de células-tronco. Objetivo: O estudo teve por objetivo avaliar a eficácia da omentopexia na neovascularização e na doação de células tronco de corações suínos previamente infartados, a partir da análise imunohistoquímica do CD34. Método: O infarto do miocárdio foi gerado em 4 suínos, por ligadura do 1°e 2° ramos marginais da artéria circunflexa. Em 3 animais realizou-se abrasão cuidadosa do epicárdio infartado seguido de múltiplas perfurações miocárdicas e a mobilização do omento da cavidade abdominal para o mediastino, envolvendo a área infartada e as perfurações. No quarto animal não foi realizado a omentopexia sendo realizado apenas a abrasão e perfuração da área infartada. Todos os animais foram eutanasiados ao 30º dia pós operatório e os corações retirados para avaliação macroscópica, microscópica e Imunohistoquímica do CD34. Resultados: Nas amostras do grupo submetido a omentopexia, ocorreu um aumento de 60% da angiogênese, sendo que nas amostras do animal controle houve marcação mínima. Foram avaliadas quatro amostras de diferentes sítios de cada coração dos animais, totalizando 16 amostras histopatológicas. Todas as amostras foram imunomarcadas para CD-34. Conclusões: O omento mostrou-se eficiente na indução de neovascularização pela presença de células tronco, vista através da marcação do CD34, demonstrando grande potencial como futura terapêutica para restaurar áreas de miocárdio isquêmico.

Fast growth rate of a right atrial myxoma.

Primary cardiac tumors are rare, with an incidence between 0.0017 and 0.19%, and are asymptomatic in up to 72% of cases. Approximately 75% of tumors are benign, and nearly 50% of these are myxomas. Concerning location, 75% of myxomas are in the left atrium, 15 to 20% in the right atrium, and more rarely in the ventricles. The finding of cardiac myxomas usually implies immediate surgical excision to prevent embolic events and sudden cardiac death. Reports with documented growth rate are rare, and the actual growth rate remains a controversial issue. We report the rapid growth rate of a right atrial myxoma in an oligosymptomatic 69-year-old patient, with negative previous echocardiographic history in the last two years, who refused surgery upon diagnosis, enabling monitoring of myxoma growth.

Fast growth rate of a right atrial myxoma

ABSTRACT Primary cardiac tumors are rare, with an incidence between 0.0017 and 0.19%, and are asymptomatic in up to 72% of cases. Approximately 75% of tumors are benign, and nearly 50% of these are myxomas. Concerning location, 75% of myxomas are in the left atrium, 15 to 20% in the right atrium, and more rarely in the ventricles. The finding of cardiac myxomas usually implies immediate surgical excision to prevent embolic events and sudden cardiac death. Reports with documented growth rate are rare, and the actual growth rate remains a controversial issue. We report the rapid growth rate of a right atrial myxoma in an oligosymptomatic 69-year-old patient, with negative previous echocardiographic history in the last two years, who refused surgery upon diagnosis, enabling monitoring of myxoma growth.

Congestive Hepatopathy Secondary to Right Ventricular Hypertrophy Related to Monocrotaline-Induced Pulmonary Arterial Hypertension.

Heart dysfunction and liver disease often coexist. Among the types of cardiohepatic syndrome, Type 2 is characterized by the chronic impairment of cardiac function, leading to chronic liver injury, referred to as congestive hepatopathy (CH). In this study, we aimed to establish a rat model of CH secondary to right ventricular hypertrophy (RVH) related to monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). Fifty male Wistar rats were divided into four groups and randomly assigned to control and experimental groups. Three experimental groups were submitted to intraperitoneal MCT inoculation (60 mg/kg) and were under its effect for 15, 30 and 37 days. The animals were then sacrificed, obtaining cardiac and hepatic tissues for anatomopathological and morphometric analysis. At macroscopic examination, the livers in the MCT groups presented a nutmeg-like appearance. PAH produced marked RVH and dilatation in the MCT groups, characterized by a significant increase in right ventricular free wall thickness (RVFWT) and chamber area. At histological evaluation, centrilobular congestion was the earliest manifestation, with preservation of the hepatocytes. Centrilobular hemorrhagic necrosis was observed in the groups exposed to prolonged MCT. Sinusoidal dilatation was markedly increased in the MCT groups, quantified by the Sinusoidal Lumen Ratio (SLR). The Congestive Hepatic Fibrosis Score and the Centrilobular Fibrosis Ratio (CFR) were also significantly increased in the MCT30 group. Hepatic atrophy, steatosis, apoptotic bodies and, rarely, hydropic swelling were also observed. SLR correlated strongly with CFR and RVFWT, and CFR correlated moderately with RVFWT. Our rat model was able to cause CH, related to monocrotaline-induced PAH and RVH; it was feasible, reproducible, and safe.

SOFTWARE-ASSISTED IMAGE ANALYSIS FOR IDENTIFICATION AND QUANTIFICATION OF HEPATIC SINUSOIDAL DILATATION AND CENTRILOBULAR FIBROSIS.

BACKGROUND: Heart dysfunction and liver disease often coexist because of systemic disorders. Any cause of right ventricular failure may precipitate hepatic congestion and fibrosis. Digital image technologies have been introduced to pathology diagnosis, allowing an objective quantitative assessment. The quantification of fibrous tissue in liver biopsy sections is extremely important in the classification, diagnosis and grading of chronic liver disease. AIM: To create a semi-automatic computerized protocol to quantify any amount of centrilobular fibrosis and sinusoidal dilatation in liver Masson's Trichrome-stained specimen. METHOD: Once fibrosis had been established, liver samples were collected, histologically processed, stained with Masson's trichrome, and whole-slide images were captured with an appropriated digital pathology slide scanner. After, a random selection of the regions of interest (ROI's) was conducted. The data were subjected to software-assisted image analysis (ImageJ®). RESULTS: The analysis of 250 ROI's allowed to empirically obtain the best application settings to identify the centrilobular fibrosis (CF) and sinusoidal lumen (SL). After the establishment of the colour threshold application settings, an in-house Macro was recorded to set the measurements (fraction area and total area) and calculate the CF and SL ratios by an automatic batch processing. CONCLUSION: Was possible to create a more detailed method that identifies and quantifies the area occupied by fibrous tissue and sinusoidal lumen in Masson's trichrome-stained livers specimens.

Software-assisted image analysis for identification and quantification of hepatic sinusoidal dilatation and centrilobular fibrosis / Análise da imagem histológica assistida por software para identificação e quantificação de dilatação sinusoidal e fibrose hepática centrolubular

ABSTRACT Background: Heart dysfunction and liver disease often coexist because of systemic disorders. Any cause of right ventricular failure may precipitate hepatic congestion and fibrosis. Digital image technologies have been introduced to pathology diagnosis, allowing an objective quantitative assessment. The quantification of fibrous tissue in liver biopsy sections is extremely important in the classification, diagnosis and grading of chronic liver disease. Aim: To create a semi-automatic computerized protocol to quantify any amount of centrilobular fibrosis and sinusoidal dilatation in liver Masson's Trichrome-stained specimen. Method: Once fibrosis had been established, liver samples were collected, histologically processed, stained with Masson's trichrome, and whole-slide images were captured with an appropriated digital pathology slide scanner. After, a random selection of the regions of interest (ROI's) was conducted. The data were subjected to software-assisted image analysis (ImageJ®). Results: The analysis of 250 ROI's allowed to empirically obtain the best application settings to identify the centrilobular fibrosis (CF) and sinusoidal lumen (SL). After the establishment of the colour threshold application settings, an in-house Macro was recorded to set the measurements (fraction area and total area) and calculate the CF and SL ratios by an automatic batch processing. Conclusion: Was possible to create a more detailed method that identifies and quantifies the area occupied by fibrous tissue and sinusoidal lumen in Masson's trichrome-stained livers specimens.

Resumo Racional: Tecnologias de imagem digital têm sido introduzidas ao diagnóstico patológico, permitindo avaliações quantitativas objetivas. A quantificação de tecido fibroso em biópsias de fígado é extremamente importante para a classificação, diagnóstico e graduação de doenças crônicas hepáticas. Objetivo: Criar um protocolo computadorizado semi-automático para quantificação de fibrose centrolobular e dilatação sinusoidal em amostras de fígado coradas por Tricrômico de Masson. Método: Uma vez instaurada a fibrose, amostras de fígado foram coletadas, processadas histologicamente, coradas por Tricrômico de Masson e WSI (Whole Slide Images) foram capturadas por scanner digital patológico apropriado. Uma seleção aleatória das regiões de interesse (ROI) foi realizada. Os dados foram submetidos a uma análise de imagem assistida por software (ImageJ®). Resultados: A análise de 250 ROIs permitiu obter-se empiricamente as melhores configurações capazes de identificar fibrose centrolobular (FC) e lúmen sinusoidal (LS). Após o estabelecimento das configurações de padrão de cor, uma Macro de autoria própria foi gravada para definir as medidas (área da fração e área total) e calcular as razões de FC e LS por processamento em grupo/lote (batch mode). Conclusão: Foi possível criar um método detalhado capaz de identificar e quantificar a área ocupada por tecido fibroso e lúmen sinusoidal em espécimes de fígado coradas por Tricrômico de Masson.

Modelo experimental de infarto agudo do miocárdio em coelhos / Experimental model of acute myocardial infarction in rabbits

Relacionado às doenças cardiovasculares, o infarto agudo do miocárdio (IAM) é a primeira causa de morte entre pacientes com doença coronariana em todo o mundo. Estudos com animais são utilizados devido à similaridade com a fisiologia e anatomia humanas. Relatos demostram utilização experimental com coelhos, pois a sua anatomia coronariana é similar aos humanos. Esta pesquisa teve por objetivo reproduzir e validar o modelo experimental controlado de IAM da parede apical anterolateral do ventrículo esquerdo em coelhos através da ligadura do ramo da artéria coronária esquerda. Foi selecionado um coelho macho para indução de IAM por ligadura coronariana. A intervenção cirúrgica consistiu na ligadura do ramo coronariano por meio de toracotomia póstero-lateral esquerda. O coração foi submetido à avaliação anatomopatológica e morfométrica para se estimar o volume percentual infartado. Em conclusão, o IAM foi alcançado com a ligadura coronariana controlada, histologicamente transmural extenso, mostrando-se eficaz e reprodutível para avaliação de novas intervenções terapêuticas e abordagens regenerativas.

Related to cardiovascular diseases, acute myocardial infarction (AMI) is the leading cause of death among patients with coronary artery disease worldwide. Animal studies are used because of their similarity to human physiology and anatomy. Reports demonstrate experimental use with rabbits, as their coronary anatomy is similar to humans. This research aimed to reproduce and validate the controlled experimental model of AMI of the anterolateral apical wall of the left ventricle in rabbits through ligation of the branch of the left coronary artery. A male rabbit was selected for induction of AMI by coronary ligation. Surgical intervention consisted of ligation of the coronary branch through a left posterolateral thoracotomy. The heart was submitted to anatomopathological and morphometric evaluation to estimate the infarcted percentage volume. In conclusion, AMI was achieved with controlled, histologically extensive transmural coronary ligation, proving to be effective and reproducible for the evaluation of new therapeutic interventions and regenerative approaches.

Infarto do miocárdio durante a pandemia de Covid-19: Análise comparativa em cinco capitais brasileiras / Myocardial infarction during the Covid-19 pandemic: Comparative analysis in five brazilian capitals

Na tentativa de controle de transmissão da COVID-19, os órgãos de saúde recomendaram isolamento domiciliar, distanciamento social e suspensão de serviços hospitalares não urgentes. Grande parte da população relutou em buscar atendimento médico. A hipótese levantada é que houve redução na incidência de internamentos e aumento na mortalidade por infarto agudo do miocárdio durante a pandemia. Este estudo procurou comparar e analisar a incidência dos internamentos e mortalidade por infarto agudo do miocárdio em cinco cidades brasileiras durante a pandemia (2020/2021) com um mesmo período (2019/2020) sem pandemia. É estudo ecológico no qual foram analisados registros comparativos da incidência de internamentos e mortalidade por infarto nas cinco capitais brasileiras. Em conclusão, houve decréscimo na incidência de internamentos durante a pandemia em todas as capitais analisadas, exceto Campo Grande, e redução na mortalidade por infarto agudo do miocárdio em todas as capitais.

In an attempt to control the transmission of COVID-19, health state agency recommended home isolation, social distancing and suspension of non-urgent hospital services. Much of the population was reluctant to seek medical attention. The hypothesis raised is that there was a reduction in the incidence of hospitalizations and an increase in mortality from acute myocardial infarction during the pandemic. This study sought to compare and analyze the incidence of hospitalizations and mortality from acute myocardial infarction in five Brazilian cities during the pandemic (2020/2021) with the same period (2019/2020) without. It is an ecological study in which comparative records of the incidence of hospitalizations and mortality from infarction in the five Brazilian capitals were analyzed. In conclusion, there was a decrease in the incidence of hospitalizations during the pandemic in all capitals analyzed, except Campo Grande, and a reduction in mortality from acute myocardial infarction in all capitals.

Dano histológico renal em modelo experimental de hipertrofia ventricular direita induzida por monocrotalina / Renal histological damage in an experimental model of monocrotalin-induced right ventricular hypertrophy

Monocrotalina, alcalóide tóxico obtido de plantas do gênero crotalaria, pode ter potencial efeito tóxico em órgãos do corpo humano, como rins, pulmões, coração, fígado e outros efeitos. O objetivo deste estudo foi avaliar o dano renal causado pela exposição à monocrotalina. Trata-se de estudo experimental em ratos divididos em 4 grupos, um dos quais recebeu injeção de soro fisiológico e os outros três inoculação de monocrotalina, com tempos diferentes para sacrifício; subsequentemente, estudo histológico foi feito a fim de evidenciar as lesões renais. Em conclusão, constatou-se que houve lesão renal. Contudo, não foi possível afirmar o mecanismo exato responsável por elas, ou seja, se foram decorrentes da ação tóxica direta da monocrotalina, ou se, também, esteve relacionado a outros fatores sistêmicos.

Monocrotaline, a toxic alkaloid obtained from plants of the Crotalaria genus, may have a potential toxic effect on human body organs, such as kidneys, lungs, heart, liver and other effects. The aim of this study was to evaluate the kidney damage caused by exposure to monocrotaline. This is an experimental study in rats divided into 4 groups, one of which received saline injection and the other three received monocrotaline inoculation, with different times for sacrifice; subsequently, a histological study was performed in order to evidence renal lesions. In conclusion, it was found that there was kidney damage. However, it was not possible to state the exact mechanism responsible for them, that is, if they were due to the direct toxic action of monocrotaline, or if it was also related to other systemic factors.

Análise dos fatores de risco para déficit neurológico em fraturas da coluna vertebral torácica e lombar / Analysis of risk factors for neurological deficit in fractures of the thoracic and lumbar vertebral spine

Responsáveis por 89% de lesões neurológicas, as fraturas de coluna vertebral torácica e lombar, quando analisadas perante os fatores de risco para déficit neurológico, apresentam associação controversa. Apesar da relação contestável, estudos apontam que as características morfológicas dessas lesões estão associadas ao grau de déficit neurológico e funcionam como guia para a estratégia terapêutica. O objetivo deste estudo foi identificar quais os fatores de risco para déficit neurológico nas fraturas da coluna vertebral torácica e lombar. É estudo transversal, observacional e individuado, no qual foram analisados 150 pacientes. Em conclusão, demonstrou-se que os subtipos de fratura A são fatores de risco para déficit neurológico e determinantes da conduta terapêutica aplicada. Além disso, indicou relação entre a classificação do déficit neurológico e energia do trauma com a necessidade de tratamento invasivo.

Responsible for 89% of neurological injuries, fractures of the thoracic and lumbar spine, when analyzed in terms of risk factors for neurological deficit, present a controversial association. Despite the debatable relationship, studies indicate that the morphological characteristics of these lesions are associated with the degree of neurological deficit and function as a guide for the therapeutic strategy. The aim of this study was to identify the risk factors for neurological deficit in thoracic and lumbar spine fractures. It is a cross-sectional, observational and individualized study, in which 150 patients were analyzed. In conclusion, it was demonstrated that fracture subtypes A are risk factors for neurological deficit and determinants of the therapeutic approach applied. In addition, it indicated a relationship between the classification of neurological deficit and trauma energy with the need for invasive treatment.

CARVEDILOL AS PRIMARY PROPHYLAXIS FOR GASTRIC VARICEAL BLEEDING IN PORTAL HYPERTENSION MODEL IN RATS.

BACKGROUND: Portal hypertension (PH) can be measured indirectly through a hepatic vein pressure gradient greater than 5 mmHg. Cirrhosis is the leading cause for PH and can present as complications ascites, hepatic dysfunction, renal dysfunction, and esophagogastric varices, characterizing gastropathy. AIM: To evaluate the use of carvedilol as primary prophylaxis in the development of collateral circulation in rats submitted to the partial portal vein ligament (PPVL) model. METHOD: This is a combined qualitative and quantitative experimental study in which 32 Wistar rats were divided into four groups (8 animals in each): group I - cirrhosis + carvedilol (PPVL + C); group II - cirrhosis + vehicle (PPVL); group III - control + carvedilol (SO-sham-operated + C); group IV - control + vehicle (SO-sham-operated). After seven days of the surgical procedure (PPVL or sham), carvedilol (10 mg/kg) or vehicle (1 mL normal saline) were administered to the respective groups daily for seven days. RESULTS: The histological analysis showed no hepatic alteration in any group and a decrease in edema and vasodilatation in the PPVL + C group. The laboratory evaluation of liver function did not show a statistically significant change between the groups. CONCLUSION: Carvedilol was shown to have a positive effect on gastric varices without significant adverse effects.

Plexiform Lesions in an Experimental Model of Monocrotalin-Induced Pulmonary Arterial Hypertension. / Lesões Plexiformes em Modelo Experimental de Hipertensão Arterial Pulmonar Induzida por Monocrotalina.

BACKGROUND: The monocrotaline (MCT)-induced pulmonary arterial hypertension model is one of the most reproduced today, presenting as a limitation the absence of plexiform lesions, typical manifestations of the severe disease in humans. OBJECTIVE: To evaluate the severity of MCT-induced pulmonary arteriopathy by pathological findings of lung and heart tissue samples, clinical course and 37-day survival. METHODS: Fifty male Wistar rats were divided into one of the four groups - control (CG) (n = 10) and three intervention (MCT) groups. The MCT groups received intraperitoneal injection (60 mg/kg) of MCT and remained exposed to the substance for 15 days (G15, n = 10), 30 days (G30, n = 10) and 37 days (G37, n = 20). At the end of each period, the animals were sacrificed, and pulmonary and cardiac tissues were collected for anatomopathological and morphometric analysis. The Kruskal-Wallis test was used, considering a level of significance of 5%. RESULTS: In the lungs of MCT animals, lesions related to pulmonary arteriopathy were found, including muscularization of the arterioles, hypertrophy of the middle layer and concentric neointimal lesions. Complex lesions were observed in MCT groups, described as plexiform and plexiform-like lesions. Right ventricular hypertrophy was evidenced by increased thickness and diameter of the cardiomyocytes and a significant increase in the right ventricular wall thickness (p <0.0000). CONCLUSION: The MCT model was able to generate moderate-severe pulmonary arteriopathy associated with secondary right ventricular hypertrophy. The 37-day survival rate was 50%. To our knowledge, this study was the first to note the presence of complex vascular lesions, similar to those observed in patients with severe pulmonary arterial hypertension, in an isolated MCT model. (Arq Bras Cardiol. 2020; 115(3):480-490).

FUNDAMENTO: O modelo de hipertensão arterial pulmonar induzida por monocrotalina (MCT) é um dos mais reproduzidos atualmente, apresentando como limitação a ausência de lesões plexiformes, manifestações típicas da doença grave em humanos. OBJETIVO: Avaliar a gravidade da arteriopatia pulmonar induzida por MCT por meio dos achados anatomopatológicos pulmonares e cardíacos, evolução clínica e sobrevida em 37 dias. MÉTODOS: Foram utilizados 50 ratos machos Wistar divididos em quatro grupos, sendo um controle (n = 10). Os três grupos restantes foram submetidos à inoculação de MCT (60 mg/kg i.p.) e ficaram sob o seu efeito por 15 (n = 10), 30 (n = 10) e 37 dias (n = 20). Ao final de cada período, os animais foram sacrificados, obtendo-se tecidos pulmonar e cardíaco para análise anatomopatológica e morfométrica. Empregou-se o teste Kruskal-Wallis, considerando nível de significância de 5%. RESULTADOS: Nos pulmões dos animais MCT foram constatadas lesões referentes à arteriopatia pulmonar, incluindo muscularização das arteríolas, hipertrofia da camada média e lesões neointimais concêntricas. Lesões complexas foram observadas nos grupos MCT, descritas como plexiforme e do "tipo" plexiforme (plexiform-like). A hipertrofia do ventrículo direito foi constatada pelo aumento da espessura e diâmetro dos cardiomiócitos e pelo aumento significativo da espessura da parede do ventrículo direito (p<0,0000). CONCLUSÃO: O modelo foi capaz de gerar arteriopatia pulmonar moderada-grave associada à hipertrofia do ventrículo direito secundária, com sobrevida de 50% em 37 dias. De nosso conhecimento, este estudo foi o primeiro a constatar a presença de lesões vasculares complexas, semelhantes às observadas em pacientes com hipertensão arterial pulmonar grave, em modelo isolado de MCT. (Arq Bras Cardiol. 2020; 115(3):480-490).

Lesões Plexiformes em Modelo Experimental de Hipertensão Arterial Pulmonar Induzida por Monocrotalina / Plexiform Lesions in an Experimental Model of Monocrotalin-Induced Pulmonary Arterial Hypertension

Resumo Fundamento O modelo de hipertensão arterial pulmonar induzida por monocrotalina (MCT) é um dos mais reproduzidos atualmente, apresentando como limitação a ausência de lesões plexiformes, manifestações típicas da doença grave em humanos. Objetivo Avaliar a gravidade da arteriopatia pulmonar induzida por MCT por meio dos achados anatomopatológicos pulmonares e cardíacos, evolução clínica e sobrevida em 37 dias. Métodos Foram utilizados 50 ratos machos Wistar divididos em quatro grupos, sendo um controle (n = 10). Os três grupos restantes foram submetidos à inoculação de MCT (60 mg/kg i.p.) e ficaram sob o seu efeito por 15 (n = 10), 30 (n = 10) e 37 dias (n = 20). Ao final de cada período, os animais foram sacrificados, obtendo-se tecidos pulmonar e cardíaco para análise anatomopatológica e morfométrica. Empregou-se o teste Kruskal-Wallis, considerando nível de significância de 5%. Resultados Nos pulmões dos animais MCT foram constatadas lesões referentes à arteriopatia pulmonar, incluindo muscularização das arteríolas, hipertrofia da camada média e lesões neointimais concêntricas. Lesões complexas foram observadas nos grupos MCT, descritas como plexiforme e do "tipo" plexiforme (plexiform-like). A hipertrofia do ventrículo direito foi constatada pelo aumento da espessura e diâmetro dos cardiomiócitos e pelo aumento significativo da espessura da parede do ventrículo direito (p<0,0000). Conclusão O modelo foi capaz de gerar arteriopatia pulmonar moderada-grave associada à hipertrofia do ventrículo direito secundária, com sobrevida de 50% em 37 dias. De nosso conhecimento, este estudo foi o primeiro a constatar a presença de lesões vasculares complexas, semelhantes às observadas em pacientes com hipertensão arterial pulmonar grave, em modelo isolado de MCT. (Arq Bras Cardiol. 2020; 115(3):480-490)

Abstract Background The monocrotaline (MCT)-induced pulmonary arterial hypertension model is one of the most reproduced today, presenting as a limitation the absence of plexiform lesions, typical manifestations of the severe disease in humans. Objective To evaluate the severity of MCT-induced pulmonary arteriopathy by pathological findings of lung and heart tissue samples, clinical course and 37-day survival. Methods Fifty male Wistar rats were divided into one of the four groups - control (CG) (n = 10) and three intervention (MCT) groups. The MCT groups received intraperitoneal injection (60 mg/kg) of MCT and remained exposed to the substance for 15 days (G15, n = 10), 30 days (G30, n = 10) and 37 days (G37, n = 20). At the end of each period, the animals were sacrificed, and pulmonary and cardiac tissues were collected for anatomopathological and morphometric analysis. The Kruskal-Wallis test was used, considering a level of significance of 5%. Results In the lungs of MCT animals, lesions related to pulmonary arteriopathy were found, including muscularization of the arterioles, hypertrophy of the middle layer and concentric neointimal lesions. Complex lesions were observed in MCT groups, described as plexiform and plexiform-like lesions. Right ventricular hypertrophy was evidenced by increased thickness and diameter of the cardiomyocytes and a significant increase in the right ventricular wall thickness (p <0.0000). Conclusion The MCT model was able to generate moderate-severe pulmonary arteriopathy associated with secondary right ventricular hypertrophy. The 37-day survival rate was 50%. To our knowledge, this study was the first to note the presence of complex vascular lesions, similar to those observed in patients with severe pulmonary arterial hypertension, in an isolated MCT model. (Arq Bras Cardiol. 2020; 115(3):480-490)

Carvedilol as primary prophylaxis for gastric variceal bleeding in portal hypertension model in rats / Carvedilol como profilaxia de sangramento em varizes gástricas em modelo de hipertensão portal em ratos

ABSTRACT Background: Portal hypertension (PH) can be measured indirectly through a hepatic vein pressure gradient greater than 5 mmHg. Cirrhosis is the leading cause for PH and can present as complications ascites, hepatic dysfunction, renal dysfunction, and esophagogastric varices, characterizing gastropathy. Aim: To evaluate the use of carvedilol as primary prophylaxis in the development of collateral circulation in rats submitted to the partial portal vein ligament (PPVL) model. Method: This is a combined qualitative and quantitative experimental study in which 32 Wistar rats were divided into four groups (8 animals in each): group I - cirrhosis + carvedilol (PPVL + C); group II - cirrhosis + vehicle (PPVL); group III - control + carvedilol (SO-sham-operated + C); group IV - control + vehicle (SO-sham-operated). After seven days of the surgical procedure (PPVL or sham), carvedilol (10 mg/kg) or vehicle (1 mL normal saline) were administered to the respective groups daily for seven days. Results: The histological analysis showed no hepatic alteration in any group and a decrease in edema and vasodilatation in the PPVL + C group. The laboratory evaluation of liver function did not show a statistically significant change between the groups. Conclusion: Carvedilol was shown to have a positive effect on gastric varices without significant adverse effects.

RESUMO Racional: A hipertensão portal (HP), medida indiretamente através do gradiente pressórico da veia hepática >5 mmHg, tem como principal causa etiológica a cirrose. Possui como complicações a ascite, disfunção hepática, disfunção renal e varizes esofagogástricas, que caracterizam o quadro de gastropatia. Objetivo: Avaliar o uso do carvedilol como profilaxia primária no desenvolvimento da circulação colateral em ratos submetidos ao modelo de ligadura parcial de veia porta (LPVP). Método: Estudo experimental qualitativo e quantitativo no qual foram utilizados 32 ratos Wistar, divididos em quatro grupos (n=8): grupo I - cirrose + carvedilol (LPVP+C); grupo II - cirrose + veículo (LPVP); grupo III - controle + carvedilol (SO - sham-operated+C); grupo IV - controle + veículo (SO - sham-operated). Após transcorridos sete dias do procedimento cirúrgico, foi administrado carvedilol (10 mg/kg) e veículo (1mL) para os respectivos grupos por sete dias consecutivos. Resultados: A análise histológica não mostrou alteração hepática em nenhum grupo e diminuição de edema e vasodilatação no grupo LPVP+C. A avaliação laboratorial da função hepática não mostrou alteração com significância estatística entre os grupos. Conclusão: Carvedilol mostrou ser fármaco com efeito positivo no sangramento das varizes gástricas e sem efeitos adversos significantes.

INVOLVEMENT OF CATECHOLAMINES IN THE MYOCARDIUM OF RATS SUBMITTED TO EXPERIMENTAL MODEL OF PORTAL HYPERTENSION.

BACKGROUND: The role of autonomic nervous system in the development and maintenance of portal hypertension is not fully elucidated. It is known that the gene expression of norepinephrine in the superior mesenteric artery varies with time, and it may contribute for splanchnic vasodilation and its consequent hemodynamic repercussions. It is still not known exactly how the adrenergic expression behaves at the heart level in the initial stages of this process. AIM: To evaluate the immunohistochemical expression of the enzyme tyrosine hydroxylase (tyrosine 3-monooxygenase), involved in the synthesis of norepinephrine, in the myocardium of rats submitted to partial ligation of the portal vein. METHODS: Twenty-four Wistar rats were divided into two groups: Sham Operated and Portal Hypertension. The partial ligation was performed in the Portal Hypertension group, and after 1/6/24 h and 3/5/14 days the animals were euthanized. Immunohistochemical analysis was performed to quantify the expression of the stained enzyme using the ImageJ program. RESULTS: The Portal Hypertension group expressed percentages between 4.6-6% of the marked area, while the Sham Operated group varied between 4-5%. Although there was no statistical significance, the percentage stained in the Portal Hypertension group followed an increasing pattern in the first 6 h and a decreasing pattern after 24 h, which was not observed in the Sham Operated group. CONCLUSION: The expression of noradrenaline in rat myocardium during the first two weeks after partial ligation of the portal vein, with tyrosine hydroxylase as marker, did not show differences between groups over time.

Involvement of catecholamines in the myocardium of rats submitted to experimental model of portal hypertension / Envolvimento das catecolaminas no miocárdio de ratos submetidos a modelo experimental de hipertensão portal

ABSTRACT Background: The role of autonomic nervous system in the development and maintenance of portal hypertension is not fully elucidated. It is known that the gene expression of norepinephrine in the superior mesenteric artery varies with time, and it may contribute for splanchnic vasodilation and its consequent hemodynamic repercussions. It is still not known exactly how the adrenergic expression behaves at the heart level in the initial stages of this process. Aim: To evaluate the immunohistochemical expression of the enzyme tyrosine hydroxylase (tyrosine 3-monooxygenase), involved in the synthesis of norepinephrine, in the myocardium of rats submitted to partial ligation of the portal vein. Methods: Twenty-four Wistar rats were divided into two groups: Sham Operated and Portal Hypertension. The partial ligation was performed in the Portal Hypertension group, and after 1/6/24 h and 3/5/14 days the animals were euthanized. Immunohistochemical analysis was performed to quantify the expression of the stained enzyme using the ImageJ program. Results: The Portal Hypertension group expressed percentages between 4.6-6% of the marked area, while the Sham Operated group varied between 4-5%. Although there was no statistical significance, the percentage stained in the Portal Hypertension group followed an increasing pattern in the first 6 h and a decreasing pattern after 24 h, which was not observed in the Sham Operated group. Conclusion: The expression of noradrenaline in rat myocardium during the first two weeks after partial ligation of the portal vein, with tyrosine hydroxylase as marker, did not show differences between groups over time.

RESUMO Racional: O papel do sistema nervoso autônomo na hipertensão portal não está completamente elucidado. Sabe-se que, nessa condição, a expressão gênica da norepinefrina na artéria mesentérica superior modifica-se com o tempo, podendo ser importante contribuinte para a vasodilatação esplâncnica e suas repercussões hemodinâmicas. Apesar dos estudos sobre as repercussões cardiovasculares na hipertensão portal, ainda não se sabe como a expressão adrenérgica se comporta a nível cardíaco nas etapas iniciais desse processo. Objetivo: Avaliar a expressão imunoistoquímica da enzima tirosina hidroxilase (tirosina 3-mono-oxigenase), relacionada à síntese da norepinefrina, no miocárdio de ratos submetidos à ligadura parcial da veia porta. Métodos: Foram utilizados 24 ratos, distribuídos em dois grupos: Sham Operated e Hipertensão Portal. A ligadura parcial da veia porta foi realizada apenas no grupo Hipertensão Portal e, após 1/6/24 h e 3/5/14 dias, os animais foram eutanasiados. Foi feita a análise imunoistoquímica para quantificar a expressão da enzima corada, utilizando o programa ImageJ. Resultados: No grupo Hipertensão Portal, o miocárdio expressou percentuais entre 4,6-6% de área marcada, enquanto que no grupo Sham Operated variou entre 4-5%, sem significância estatística. Apenas no grupo Hipertensão Portal, a porcentagem corada pela enzima seguiu padrão crescente nas primeiras 6 h e decrescente após 24 h. Conclusão: A expressão da noradrenalina no miocárdio de ratos durante as primeiras duas semanas após a ligadura parcial da veia porta, tendo como marcador a enzima tirosina hidroxilase, não apresentou diferenças entre grupos ao longo do tempo.

Biocompatibilidade do polímero da mamona comparada ao implante de titânio para corações artificiais: estudo experimental em cobaias / Biocompatibility of Ricinus comunnis polymer compared to titanium implant used in artificial hearts: experimental study in guinea pigs

OBJETIVO: Determinar se a reação tecidual do implante retroperitoneal do polímero de óleo de mamona (Pm) é significativa ou não por meio de análise histopatológica, tendo como controle o implante de titânio (Ti). MÉTODOS: Estudo experimental, intervencionista e randomizado com 32 cobaias. Os animais foram divididos em quatro grupos iguais e eutanasiados com 7, 20, 30 e 40 dias após o ato cirúrgico. Foram confeccionadas lâminas em hematoxilina-eosina e em tricrômio de Masson. Na comparação dos tipos de material em relação a variáveis quantitativas, foi considerado o teste não-paramétrico de Wilcoxon. Em relação a essas variáveis, os grupos definidos pelo dia do sacrifício foram comparados usando-se o teste não-paramétrico de Kruskal-Wallis. Os resultados obtidos no estudo da fibrose foram expressos por frequências e percentuais. Para a comparação entre os grupos definidos pelo dia do sacrifício, em relação a variáveis qualitativas dicotômicas da fibrose, foi considerado o teste exato de Fisher. Para avaliar a diferença entre os materiais titânio e polímero em cada grupo, ainda em se tratando da fibrose, foi considerado o teste binomial. Valores de P<0,05 indicaram significância estatística. RESULTADOS: A análise das variáveis quantitativas não demonstrou diferença nas reações teciduais entre os materiais (P>0,05). A análise da variável qualitativa também não demonstrou diferença entre as reações teciduais dos materiais (P>0,05). CONCLUSÃO: Não foi encontrada significância estatística entre a reação tecidual do Pm e do Ti.

OBJECTIVE: The aim of the present investigation is to determine if the tissue reaction to the Riccinus communis (mamona) polymer has significant statistical difference compared to the tissue reaction provoked by the titanium implant. METHODS: Thirty two Cavia porcellus were divided into four groups containing eight animals each one. We implanted the two types of materials in the retroperitoneal space of all the animals. They were sacrificed at 7, 20, 30 and 40 days after surgery and the samples were submitted to histological study. RESULTS: The quantitative analysis did not show difference between the tissue reaction of the two materials (P>0.05). The analysis of the qualitative variable also did not show difference between the tissue reaction of the materials (P>0.05). CONCLUSION: Macroscopic and microscopic results showed that the castor oil polymer implant has no significant statistical difference compared to the titanium implant tissue reaction.

Biocompatibility of Ricinus comunnis polymer compared to titanium implant used in artificial hearts. Experimental study in guinea pigs.

OBJECTIVE: The aim of the present investigation is to determine if the tissue reaction to the Riccinus communis (mamona) polymer has significant statistical difference compared to the tissue reaction provoked by the titanium implant. METHODS: Thirty two Cavia porcellus were divided into four groups containing eight animals each one. We implanted the two types of materials in the retroperitoneal space of all the animals. They were sacrificed at 7, 20, 30 and 40 days after surgery and the samples were submitted to histological study. RESULTS: The quantitative analysis did not show difference between the tissue reaction of the two materials (P>0.05). The analysis of the qualitative variable also did not show difference between the tissue reaction of the materials (P>0.05). CONCLUSION: Macroscopic and microscopic results showed that the castor oil polymer implant has no significant statistical difference compared to the titanium implant tissue reaction.