Analysis of intrinsic cardiac neuron activity in relation to neurogenic atrial fibrillation and vagal stimulation

La fibrillation auriculaire est le trouble du rythme le plus fréquent chez l'homme. Elle conduit souvent à de graves complications telles que l'insuffisance cardiaque et les accidents vasculaires cérébraux. Un mécanisme neurogène de la fibrillation auriculaire mis en évidence. L'induction de tachyarythmie par stimulation du nerf médiastinal a été proposée comme modèle pour étudier la fibrillation auriculaire neurogène. Dans cette thèse, nous avons étudié l'activité des neurones cardiaques intrinsèques et leurs interactions à l'intérieur des plexus ganglionnaires de l'oreillette droite dans un modèle canin de la fibrillation auriculaire neurogène. Ces activités ont été enregistrées par un réseau multicanal de microélectrodes empalé dans le plexus ganglionnaire de l'oreillette droite. L'enregistrement de l'activité neuronale a été effectué continument sur une période de près de 4 heures comprenant différentes interventions vasculaires (occlusion de l'aorte, de la veine cave inférieure, puis de l'artère coronaire descendante antérieure gauche), des stimuli mécaniques (toucher de l'oreillette ou du ventricule) et électriques (stimulation du nerf vague ou des ganglions stellaires) ainsi que des épisodes induits de fibrillation auriculaire. L'identification et la classification neuronale ont été effectuées en utilisant l'analyse en composantes principales et le partitionnement de données (cluster analysis) dans le logiciel Spike2. Une nouvelle méthode basée sur l'analyse en composante principale est proposée pour annuler l'activité auriculaire superposée sur le signal neuronal et ainsi augmenter la précision de l'identification de la réponse neuronale et de la classification. En se basant sur la réponse neuronale, nous avons défini des sous-types de neurones (afférent, efférent et les neurones des circuits locaux). Leur activité liée à différents facteurs de stress nous ont permis de fournir une description plus détaillée du système nerveux cardiaque intrinsèque. La majorité des neurones enregistrés ont réagi à des épisodes de fibrillation auriculaire en devenant plus actifs. Cette hyperactivité des neurones cardiaques intrinsèques suggère que le contrôle de cette activité pourrait aider à prévenir la fibrillation auriculaire neurogène. Puisque la stimulation à basse intensité du nerf vague affaiblit l'activité neuronale cardiaque intrinsèque (en particulier pour les neurones afférents et convergents des circuits locaux), nous avons examiné si cette intervention pouvait être appliquée comme thérapie pour la fibrillation auriculaire. Nos résultats montrent que la stimulation du nerf vague droit a été en mesure d'atténuer la fibrillation auriculaire dans 12 des 16 cas malgré un effet pro-arythmique défavorable dans 1 des 16 cas. L'action protective a diminué au fil du temps et est devenue inefficace après ~ 40 minutes après 3 minutes de stimulation du nerf vague.

Oxidative stress and growth-regulating intracellular signaling pathways in cardiac myocytes

The toxic effects of oxidative stress on cells (including cardiac myocytes, the contractile cells of the heart) are well known. However, an increasing body of evidence has suggested that increased production of reactive oxygen species (ROS) promotes cardiac myocyte growth. Thus, ROS may be 'second messenger' molecules in their own right, and growth-promoting neurohumoral agonists might exert their effects by stimulating production of ROS. The authors review the principal growth-promoting intracellular signaling pathways that are activated by ROS in cardiac myocytes, namely the mitogen-activated protein kinase cascades (extracellular signal-regulated kinases 1/2, c-Jun N-terminal kinases, and p38-mitogen-activated protein kinases) and the phosphoinositide 3-kinase/protein kinase B (Akt) pathway. Possible mechanisms are discussed by which these pathways are activated by ROS, including the oxidation of active site cysteinyl residues of protein and lipid phosphatases with their consequent inactivation, the potential involvement of protein kinase C or the apoptosis signal-regulating kinase 1, and the current models for the activation of the guanine nucleotide binding protein Ras.

Right coronary artery fistula to the coronary sinus and right atrium associated with giant right coronary enlargement detected by transthoracic echocardiography

We present the case of a 54-year-old female with a previous history of lung fibrosis secondary to methotrexate used for rheumatoid arthritis who was referred to cardiology evaluation due to precordial pain. Echocardiography showed biatrial enlargement with an enlarged coronary sinus and tubular image posterior to the heart. On the coronary angiogram, the right coronary artery was enlarged, and a distal fistula was identified. The patient underwent a contrast enhanced cardiac computed tomography which demonstrated an aneurysmatic right coronary artery with a distal fistula to the right atrium and coronary sinus. As the chest pain did not recur and there was a high risk of the intervention to correct coronary fistula, the patient remained on conservative treatment.

High-resolution electrocardiography in the diagnosis of arrhythmogenic right ventricular cardiomyopathy in Boxer dogs

Com o objetivo de avaliar a importância da eletrocardiografia de alta resolução no diagnóstico da cardiomiopatia arritmogênica do ventrículo direito do Boxer, 20 cães sem evidências de doença cardíaca estrutural à avaliação ecodopplercardiográfica foram agrupados de acordo com a frequência de arritmias ventriculares, avaliadas pela eletrocardiografia ambulatorial de 24 horas, e submetidos ao exame eletrocardiográfico de alta resolução. Duração do complexo QRS filtrado, duração dos sinais de baixa amplitude (menor que 40µV) dos últimos 40 milissegundos do complexo QRS e raiz quadrada média da voltagem ao quadrado dos últimos 40 milissegundos do complexo QRS (RMS40) foram as variáveis avaliadas. Não foram observadas diferenças significativas entre os grupos em relação às variáveis estudadas. Sendo assim, os resultados do presente estudo sugerem que a eletrocardiografia de alta resolução não é uma ferramenta útil no auxílio diagnóstico da cardiomiopatia arritmogênica do ventrículo direito dos cães da raça Boxer que não apresentam alterações miocárdicas evidentes ou disfunção sistólica.

Cardiac function in dogs with chronic Chagas cardiomyopathy undergoing autologous stem cell transplantation into the coronary arteries

This study assessed the effects of a single intracoronary injection of autologous stem cells on the cardiac function of dogs with Chagas cardiomyopathy. Bone-marrow-derived stem cells were delivered into the right and left coronary arteries of 5 mature dogs with mildly compromised cardiac function due to chronic Chagas cardiomyopathy. Blood pressure and electrocardiographic and echocardiographic parameters were recorded at monthly intervals for 6 mo in the 3 dogs that survived. Although no changes were observed in the electrocardiogram and blood pressure, there was a significant increase in peak velocity of aortic flow 3 mo after stem cell transplantation. Pre-ejection period, isovolumic relaxation time, and the Tei index of myocardial performance were reduced significantly 4 mo after the procedure. All significant changes persisted to the end of the study. The results suggest that the transplantation of autologous bone-marrow-derived stem cells into the coronary arteries of dogs with Chagas cardiomyopathy may have a beneficial effect but the small number of dogs studied was a limitation.

Heart failure due to right ventricular metastatic neuroendocrine tumor

We report a case of a female patient that was referred to our service with progressive weakness and dyspnea. Three years ago, she had been submitted to hysterectomy and salpingo-oforectomy followed by adjuvant radiotherapy due to uterine cervix neuroendocrine tumor. Two-dimensional echocardiography showed a dense sessile mass in the right ventricle causing right and left ventricular filling restriction. Despite chemotherapy the patient died and necropsy confirmed metastases from neuroendocrine tumor to the right ventricle. (C) 2007 Elsevier B.V. All rights reserved.

Combined exercise training in asymptomatic elderly with controlled hypertension: Effects on functional capacity and cardiac diastolic function

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

The unequal influences of the left and right vagi on the control of the heart and pulmonary artery in the rattlesnake, Crotalus durissus

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Vagal control of heart rate and cardiac shunts in reptiles: Relation to metabolic state

The vagus is clearly of primary importance in the regulation of reptilian cardiorespiratory systems. Vagal control of pulmonary blood flow and cardiac shunts provides reptiles with an additional means of regulating arterial oxygen levels that is not present in endothermic vertebrates (birds and mammals). Within a given species, there exists a clear correlation between withdrawal of vagal tone on the cardiovascular system and elevated metabolic rate. Undisturbed and resting reptiles are normally characterised by high vagal tone, low pulmonary blood flow and large right-left (R-L) cardiac shunts. The low oxygen levels that result from the large R-L shunt may serve to regulate metabolism. However, when metabolism is increased by temperature, exercise or digestion, the R-L cardiac shunt is reduced, which serves to increase oxygen delivery. This response is partially elicit ed by reduction of vagal tone. Interspecies comparisons reveal a similar pattern. Thus, species that are able to sustain the highest metabolic rates possess the highest degree of anatomical ventricular separation and, therefore, less cardiac shunting. It is interesting to note that when cardiac shunts occur in mammals, due for example to developmental defects, they are associated with reduced maximal metabolic rates and impaired exercise tolerance. It appears, therefore, that full separation of ventricular blood flows was a prerequisite for the evolution of high aerobic metabolic rates and exercise stamina in mammals and birds.

Arteriovenous fistula between the right internal mammary artery and the subclavian vein: percutaneous closure with detachable ballooncatheter embolization

A case of iatrogenic fistula from the right internal mammary artery to the subclavian vein following subclavian vein catheterization is reported. The patient had undergone percutaneous Intracath catheterization of the subclavian vein to treat hypovolemic shock during the surgical treatment of ectopic pregnancy. She had remained symptom-free for 7 years and then started to complain of effort dyspnea. The patient was found to have a thrill and a bruit at the subclavian region, and arteriography demonstrated a fistula between the right internal mammary artery and the subclavian vein. The fistula was successfully closed by embolization with a percutaneous detachable balloon catheter. © 1993.

Sildenafil for pulmonary hypertension treatment after cardiac surgery

Objective: To report on the use of sildenafil for pulmonary hypertension treatment of a newborn patient after cardiac surgery. Description: A female, full term newborn infant with diagnosis of double outlet right ventricle, pulmonary hypoplasia and subaortic ventricular septal defect, was submitted to Blalock surgery in the first week of life. In postoperative the newborn had pulmonary hypertension and persistent hypoxia, without response to nitric oxide, but with improved oxygenation after continuous intravenous infusion of prostaglandin E1. After several failed attempts to discontinue prostaglandin E1, oral sildenafil was used. There was a decrease in pulmonary vascular resistance with consequent oxygenation improvement and 48 hours later it was possible to discontinue prostaglandin E1 infusion. Comments: Sildenafil can be an alternative therapy for pulmonary hypertension, especially when there is no response to conventional therapy. Copyright © 2005 by Sociedade Brasileira de Pediatria.

Cardiac baroreflex is already blunted in eight weeks old spontaneously hypertensive rats

Background. The literature did not evidence yet with which age spontaneously hypertensive rats (SHR) start to present baroreflex reduction. We endeavored to evaluate the baroreflex function in eight-week-old SHR. Methods. Male Wistar Kyoto (WKY) normotensive rats and SHR aged eight weeks were studied. Baroreflex was calculated as the variation of heart rate (HR) divided by the mean arterial pressure (MAP) variation (HR/MAP) tested with a depressor dose of sodium nitroprusside (SNP, 50 g/kg) and with a pressor dose of phenylephrine (PHE, 8 g/kg) in the right femoral venous approach through an inserted cannula in the animals. Significant differences for p < 0.05. Results. Baseline MAP (p < 0.0001) and HR (p = 0.0028) was higher in SHR. Bradycardic peak was attenuated in SHR (p < 0.0001), baroreflex gain tested with PHE was also reduced in the SHR group (p = 0.0012). PHE-induced increase in MAP was increased in WKY compared to SHR (p = 0.039). Bradycardic reflex responses to intravenous PHE was decreased in SHR (p < 0.0001). Conclusion. Eight weeks old SHR already presents impairment of the parasympathetic component of baroreflex. © 2010 Cisternas et al; licensee BioMed Central Ltd.

Cardiac remodeling induced by 13-cis retinoic acid treatment in acne patients

Background: Currently, 13-cis-retinoic acid (13-cis-RA) is the most effective therapy for acne. Isotretinoin, a first-generation synthetic 13-cis-RA compound, is associated with numerous adverse effects. To investigate the cardiac effects of 13-cis-RA, acne patients receiving 13-cis-RA were studied. Methods: Twenty male patients with acne were enrolled in the study. Patients were treated with a dose of 0.5 mg/kg/d of isotretinoin. All participants were assessed prior to treatment and after 10 weeks of therapy with Doppler-echocardiogram. Results: Patients showed reductions in right atrium vertical diameter, left atrium longitudinal diameter, left atrium volume and left ventricular diastolic diameter over the course of treatment. Significant increases in interventricular septum diastolic thickness, posterior wall diastolic thickness, relative wall relative thickness and left ventricle (LV) mass were observed. The LV mass index showed an increase in ventricular mass and a decrease in the cavity size. Examining LV systolic function, a decrease was observed for the cardiac index. Conclusion: In this study, 10 weeks of 13-cis-RA therapy at a dose of 0.5 mg/kg/d was found to promote concentric-type heart remodeling due to the occurrence of two associated events: heart hypertrophy and hypovolemia. © 2011 Elsevier B.V. All rights reserved.

Long-term cardiac changes in patients with systemic lupus erythematosus

Background: The aim of this study was evaluate the late-onset repercussions of heart alterations of patients with systemic lupus erythematosus (SLE) after a 13-year follow up. Methods. A historical prospective study was carried out involving the analysis of data from the charts of patients with a confirmed diagnosis of lupus in follow up since 1998. The 13-year evolution was systematically reviewed and tabulated to facilitate the interpretation of the data. Results: Forty-eight patient charts were analyzed. Mean patient age was 34.5 ± 10.8 years at the time of diagnosis and 41.0 ± 10.3 years at the time of the study (45 women and 3 men). Eight deaths occurred in the follow-up period (two due to heart problems). Among the alterations found on the complementary exams, 46.2% of cases demonstrated worsening at reevaluation and four patients required a heart catheterization. In these cases, coronary angioplasty was performed due to the severity of the obstructions and one case required a further catheterization, culminating in the need for surgical myocardial revascularization. Conclusion: The analysis demonstrated progressive heart impairment, with high rates of alterations on conventional complementary exams, including the need for angioplasty or revascularization surgery in four patients. These findings indicate the need for rigorous cardiac follow up in patients with systemic lupus erythematosus. © 2013 de Godoy et al.; licensee BioMed Central Ltd.

Impact of the length of vitamin D deficiency on cardiac remodeling.

This study was aimed to evaluate the influence of vitamin D (VD) deficiency on cardiac metabolism, morphology, and function. Thus, we investigated the relationship of these changes with the length of the nutrient restriction. Male weanling Wistar rats were allocated into 4 groups: C2 (n=24), animals were fed an AIN-93G diet with 1000 IU VD/kg of chow and were kept under fluorescent light for 2 months; D2 (n=22), animals were fed a VD-deficient AIN-93G diet and were kept under incandescent light for 2 months; C4 (n=21) animals were kept in the same conditions of C2 for 4 months; and D4 (n=23) animals were kept in the same conditions of D2 for 4 months. Biochemical analyses showed lower β-hydroxyacyl coenzyme-A dehydrogenase activity and higher lactate dehydrogenase activity in VD-deficient animals. Furthermore, VD deficiency was related to increased cytokines release, oxidative stress, apoptosis, and fibrosis. Echocardiographic data showed left ventricular hypertrophy and lower fractional shortening and ejection fraction in VD-deficient animals. Difference became evident in the lactate dehydrogenase activity, left ventricular weight, right ventricle weight, and left ventricular mass after 4 months of VD deficiency. Our data indicate that VD deficiency is associated with energetic metabolic changes, cardiac inflammation, oxidative stress, fibrosis and apoptosis, cardiac hypertrophy, left chambers alterations, and systolic dysfunction. Furthermore, length of the restriction influenced these cardiac changes.