A Remodelação do Sistema Nervoso Autônomo Cardíaco pode Desempenhar um Papel na Fibrilação Atrial: Um Estudo do Sistema Nervoso Autônomo e Receptores Miocárdicos / Cardiac Autonomic Nervous System Remodeling May Play a Role in Atrial Fibrillation: A Study of the Autonomic Nervous System and Myocardial Receptors

Resumo Fundamento Alterações do substrato elétrico e anatômico do coração são fatores que originam e perpetuam a fibrilação atrial (FA), porém, os mecanismos envolvidos não foram totalmente elucidados ainda. Objetivo: Avaliar o papel do remodelamento do sistema nervoso cardíaco intrínseco (SNCI), incluindo fibras nervosas e receptores muscarínicos e β-adrenérgicos, na FA permanente humana. Métodos Foram avaliadas 4 amostras em átrios de 13 corações obtidos em necrópsias de pacientes com doença cardíaca e FA permanente, e em 13 controles com as mesmas doenças, porém, sem FA. Utilizando imunoperoxidase e histomorfometria, quantificamos a densidade das fibras do SNCI, bem como a porcentagem positiva de miocárdio para receptores β-adrenérgicos 1, 2 e 3, receptor quinase 5 acoplado à proteína G (GRK-5), e receptores muscarínicos 1 a 5. Os resultados foram comparados usando ANOVA e ANOVA hierarquizada e ajustados pelo volume do átrio esquerdo e, para avaliação da expressão de receptores β e GRK-5, pelo uso de β-bloqueadores. Adotamos como significativo α = 0,05. Resultados Houve aumento na densidade das fibras ( p <0,01), especialmente nas fibras simpáticas ( p =0,02). Quanto aos receptores muscarínicos, só houve diferença nos M1, que estavam aumentados (5,87±4,52 vs 2,85±2,40; p =0,03). Quanto aos componentes do sistema adrenérgicos analisados, houve expressão aumentada de β-3 (37,41 vs 34,18, p =0,04) e GRK-5 (51,16 vs 47,66; p<0,01). O uso de β-bloqueadores não teve impacto na expressão de receptores beta. Conclusão O aumento na inervação do SNCI e a alteração na expressão de receptores em regiões suscetíveis de desencadear FA podem ter um papel na fibrilação atrial permanente.

Abstract Background The primary factors that originate and perpetuate atrial fibrillation (AF) are electrical and anatomical substrate alterations. However, the central mechanisms governing AF perpetuation have not been elucidated yet, which is reflected on the modest results of the treatment in patients with long persistent AF. Objective To evaluate if human intrinsic cardiac autonomic nervous system (ICANS) remodeling, including nervous system fibers and muscarinic and β-adrenergic receptors, play a role in permanent AF. Methods Heart necropsy samples from thirteen patients with heart disease and permanent AF and thirteen controls without AF were used. By using immunoperoxidase and histomorphometry quantification, we identified the following: the density of all fibers of the ICANS, sympathetic and parasympathetic fibers; and the percentage of myocardium positive for β-adrenergic receptors 1, 2 and 3; G protein-coupled receptor kinase-5 (GRK-5); and muscarinic receptors M1 to M5. The results were compared using ANOVA and nested ANOVA and were adjusted according to the left atrium volume for all variables, and β-blocker use to evaluate the expression of β-receptors and GRK-5. Results There was an overall increase in the density of fibers of the ICANS (p=0.006), especially in atrial sympathetic nerve fibers (p=0.017). Only M1 muscarinic receptors were increased (5.87 vs 2.35, p=0.032). For adrenergic receptors, the results were positive for increased expression of β-3 (37.41 vs 34.18, p=0.039) and GRK-5 (51.16 vs 47.66; p<0.001). β-blocker use had no impact on β-receptor expression. Conclusion Increased ICANS innervation and remodeling receptor expression in regions prone to triggering AF may play a role in permanent AF.

A new experimental device for transapical access of the aortic and mitral valves as well as the aorta in its various segments

Abstract Objective: To present the results of a new experimental device developed to facilitate the transapical access in endovascular treatment of structural heart diseases. It aims to reduce the risk of bleeding and complications in this type of access and demonstrate the device as a safe, fast and effective alternative. Methods: CorPoint is composed of three parts: introducer, base with coiled spring, and closing capsule. By rotating movements, the spring is introduced into the myocardium and progressively approaches the base to the surface of the heart. Guidewires and catheters are inserted through the hollow central part and, at the end of the procedure, the capsule is screwed over the base, therefore stopping any bleeding. Results: The device was implanted in 15 pigs, weighing 60 kg each, through an anterolateral thoracotomy, while catheters were introduced and guided by fluoroscopy. All animals had minimal bleeding; introducers with diameter up to 22 Fr were used and various catheters and guidewires were easily handled. After finishing the procedure, the closing capsule was attached and no bleeding was observed at the site. Conclusion: This new device has proved effective, fast and secure for the transapical access. This shows great potential for use, especially by ensuring an easier and direct access to the mitral and aortic valves; the shortest distance to be traveled by catheters; access to the ascending and descending aorta; decreased bleeding complications; decreased surgical time; and the possibility of allowing the technique to evolve and become totally percutaneous.

Effect of hypertonic saline treatment on the inflammatory response after hydrochloric acid-induced lung injury in pigs

OBJECTIVES: Hypertonic saline has been proposed to modulate the inflammatory cascade in certain experimental conditions, including pulmonary inflammation caused by inhaled gastric contents. The present study aimed to assess the potential anti-inflammatory effects of administering a single intravenous dose of 7.5% hypertonic saline in an experimental model of acute lung injury induced by hydrochloric acid. METHODS: Thirty-two pigs were anesthetized and randomly allocated into the following four groups: Sham, which received anesthesia and were observed; HS, which received intravenous 7.5% hypertonic saline solution (4 ml/kg); acute lung injury, which were subjected to acute lung injury with intratracheal hydrochloric acid; and acute lung injury + hypertonic saline, which were subjected to acute lung injury with hydrochloric acid and treated with hypertonic saline. Hemodynamic and ventilatory parameters were recorded over four hours. Subsequently, bronchoalveolar lavage samples were collected at the end of the observation period to measure cytokine levels using an oxidative burst analysis, and lung tissue was collected for a histological analysis. RESULTS: Hydrochloric acid instillation caused marked changes in respiratory mechanics as well as blood gas and lung parenchyma parameters. Despite the absence of a significant difference between the acute lung injury and acute lung injury + hypertonic saline groups, the acute lung injury animals presented higher neutrophil and tumor necrosis factor alpha (TNF-α), interleukin (IL)-6 and IL-8 levels in the bronchoalveolar lavage analysis. The histopathological analysis revealed pulmonary edema, congestion and alveolar collapse in both groups; however, the differences between groups were not significant. Despite the lower cytokine and neutrophil levels observed in the acute lung injury + hypertonic saline group, significant differences were not observed among the treated and non-treated groups. ...

Estudo Pré-Clínico de Stent com Polímero Biodegradável e Liberação Abluminal de Sirolimus / Preclinical Study of a Biodegradable Polymer-based Stent with Abluminal Sirolimus Release

Fundamento: Stents recobertos com polímeros bioabsorvíveis e fármacos apenas na face abluminal podem ser mais seguros que stents farmacológicos com polímeros permanentes. Objetivo: Relatar os resultados experimentais com o stent Inspiron(r), um stent recoberto com polímero bioabsorvível e com liberação de sirolimus apenas da face abluminal, recentemente aprovado para uso clínico. Métodos: Foram implantados 45 stents nas artérias coronárias de 15 porcos e, no 28° dia pós-implante, foram obtidos os resultados angiográficos, de ultrassonografia intracoronária e de histomorfologia. Cinco grupos foram avaliados: Grupo I (nove stents sem recobrimento); Grupo II (nove stents com polímero bioabsorvível nas faces luminal e abluminal); Grupo III (oito stents com polímero bioabsorvível na face abluminal); Grupo IV (nove stents com polímero bioabsorvível e sirolimus nas faces luminal e abluminal); e Grupo V (dez stents com polímero bioabsorvível e sirolimus na face abluminal exclusivamente). Resultados: Observamos, para os Grupos I, II, III, IV e V respectivamente: porcentual de estenose de 29 ± 20; 36 ± 14; 33 ± 19; 22 ± 13 e 26 ± 15 (p = 0,443); perda luminal tardia (em mm) de 1,02 ± 0,60; 1,24 ± 0,48; 1,11 ± 0,54; 0,72 ± 0,44 e 0,78 ± 0,39 (p = 0,253); área neointimal (em mm2) de 2,60 ± 1,99; 2,74 ± 1,51; 2,74 ± 1,30; 1,30 ± 1,14 e 0,97 ± 0,84 (p = 0,001; Grupos IV e V versus Grupos I, II e III) e porcentual de área neointimal de 35 ± 25; 38 ± 18; 39 ± 19; 19 ± 18 e 15 ± 12 (p = 0,001; Grupo IV e V versus Grupo I, II e III). Os escores de injúria e inflamação foram baixos e sem diferenças entre os grupos. Conclusão: O stent Inspiron(r) foi seguro e inibiu significativamente a hiperplasia ...

Background: Bioabsorbable polymer stents with drug elution only on the abluminal surface may be safer than durable polymer drug-eluting stents. Objective: To report the experimental findings with the Inspiron(tm) stent - a bioabsorbable polymer-coated stent with sirolimus release from the abluminal surface only, recently approved for clinical use. Methods: 45 stents were implanted in the coronary arteries of 15 pigs. On day 28 after implantation, angiographic, intracoronary ultrasonographic and histomorphological data were collected. Five groups were analyzed: Group I (nine bare-metal stents); Group II (nine coated with bioabsorbable polymer on the luminal and abluminal surfaces); Group III (eight stents coated with bioabsorbable polymer on the abluminal surface); Group IV (nine stents with bioabsorbable polymer and sirolimus on the luminal and abluminal surfaces); and Group V (ten stents with bioabsorbable polymer and sirolimus only on the abluminal surface). Results: The following results were observed for Groups I, II, III, IV and V, respectively: percentage stenosis of 29 ± 20; 36 ± 14; 33 ± 19; 22 ± 13 and 26 ± 15 (p = 0.443); late lumen loss (in mm) of 1.02 ± 0.60; 1.24 ± 0.48; 1.11 ± 0.54; 0.72 ± 0.44 and 0.78 ± 0.39 (p = 0.253); neointimal area (in mm2 )) of 2.60 ± 1.99; 2.74 ± 1.51; 2.74 ± 1.30; 1.30 ± 1.14 and 0.97 ± 0.84 (p = 0.001; Groups IV and V versus Groups I, II and III); and percentage neointimal area of 35 ± 25; 38 ± 18; 39 ± 19; 19 ± 18 and 15 ± 12 (p = 0.001; Groups IV and V versus Groups I, II and III). Injury and inflammation scores were low and with no differences between the groups. Conclusion: The Inspiron(tm) stent proved to be safe and was able to significantly inhibit the neointimal hyperplasia observed on day 28 after implantation in porcine coronary arteries. .