Étude de la fonction vasculaire et du remodelage cardiaque avant l’établissement de l’obésité et de la dyslipidémie chez les rats femelles Sprague-Dawley recevant une diète riche en gras

Des lacunes existent au niveau des connaissances concernant les modifications cardiovasculaires manifestées avant l’établissement d’obésité et en absence d’hyperlipidémie. Dans cette optique, la présente étude a testé l'hypothèse générale qui stipule que l’administration d’une diète riche en gras pour une période de 8 semaines chez les rats femelles influence négativement la fonction et le remodelage cardiaque, avant le développement de l’obésité et en absence d’hyperlipidémie et d’hyperglycémie. Afin de répondre à cette problématique, des rats femelles Sprague-Dawley ont été assignés à une diète standard (SD; 12,5% lipides, kcal) ou riche en gras (HF; 42% lipides, kcal) pour une période de 8 semaines. Cette durée était insuffisante pour induire le développement d’une dyslipidémie ou une augmentation significative de la masse corporelle chez les animaux HF(329±14g) comparativement aux rates SD (300±10g). Toutefois, une hypertension artérielle s’est développée chez les rates HF (130±4 vs 108±6 mmHg, p<0,05), accompagnée d’une altération des relaxations aortiques dépendantes de l’endothélium (relaxation maximale : 22±5% versus 53±8%, pour les animaux HF et SD respectivement, p<0,05). L’administration orale chronique de l’antioxydant resvératrol (RES; 20 mg·kg-1·jr-1) a prévenu le développement de ces altérations pathologiques, attestant d’une implication du stress oxydant. Au niveau cardiaque, le RES n’a toutefois pas inhibé le développement de fibrose périvasculaire secondaire à l’administration de la diète riche en gras. Suite à une insulte d’ischémie-reperfusion, la taille (SD : 0,29±0,09 versus HF : 0,32±0,13 cm), l’épaisseur (SD : 0,05±0,02 versus HF : 0,06±0,01 cm) et le contenu en collagène α1 type 1 (SD : 0,21±0,04 versus HF : 0,20±0,04 unités arbitraires/mm2) de la cicatrice du coeur infarci des rats HF étaient comparables au coeur infarci des rats SD. Malgré ces similitudes, le taux de décès était significativement (p<0,05) plus élevé chez les rats HF (56%) comparativement aux rats SD (5%). L’approche par électrophysiologie a démontré que l’administration de la diète riche en gras était associée à une augmentation (p<0,05) du nombre d’extrasystoles ventriculaires induites. Cette élévation de l’incidence était associé à une hyperinnervation sympathique fonctionnelle, tel que démontré par une élévation (p<0,05) de la densité des fibres neurofilament-M (HF : 2830±250 versus SD : 2020±260 μm2/mm2) et de la protéine de l’hydroxylase de la tyrosine. La fonctionnalité des jonctions intercellulaires était également atteinte, caractérisée par une latéralisation et internalisation de connexine 43 ainsi qu’une diminution de l’expression de connexine 40 au niveau des disques intercalaires. Ainsi, avant l’établissement de l’obésité et d’une dyslipidémie, les rats femelles modestement hypertendus présentent un phénotype arythmogénique cardiaque en partie dû à une hyperinnervation sympathique et une expression altérée concomitante de la distribution et de l’expression des jonctions intercellulaires. L’absence de symptômes cliniques d’obésité dans la présente étude ne fournit aucun indice au clinicien quant à la susceptibilité accrue aux arythmies ventriculaires. Ainsi, en présence d’une hypertension artérielle modérée chez un patient non-obèse, une mesure de l’activité sympathique par la quantification des niveaux circulants de catécholamines pourrait être bénéfique afin de détecter les patients à risque de mort subite.

Prolongation de l’intervalle QT corrigé chez les adultes atteints de lupus érythémateux disséminé porteurs de l’anticorps anti-Ro/SSA

La prolongation de l’intervalle électrocardiographique QT est un facteur de risque d’arythmie ventriculaire et de mort subite. Cette anomalie, retrouvée chez certains patients atteints de lupus érythémateux disséminé, pourrait contribuer à la mortalité cardiovasculaire élevée dans cette population. L’anti-Ro/SSA, un auto-anticorps retrouvé chez environ 30% des patients atteints de lupus, est associé à la présence de blocs cardiaques chez le nouveau-né et pourrait aussi augmenter le risque de prolongation pathologique de l’intervalle QT chez l’adulte. Le présent mémoire est constitué de cinq chapitres traitant de l’association potentielle entre l’anticorps anti-Ro/SSA et la prolongation de l’intervalle QT. Le premier chapitre constitue une introduction permettant de mettre en contexte les éléments essentiels à la compréhension du projet d’étude. Le deuxième chapitre constitue une revue de l’état des connaissances actuelles sur le lien potentiel entre anti-Ro/SSA et intervalle QT. Le troisième chapitre présente le projet d’étude par l’intermédiaire d’un article publié dans Arthritis Care and Research. Dans cette étude, les patients de la cohorte de lupiques du Centre Universitaire de santé McGill ont subi des électrocardiogrammes dans l’objectif d’estimer l’association entre l’anti-Ro/SSA et les anomalies électrocardiographiques, en tenant compte d’autres facteurs démographiques et cliniques. L’association entre la prolongation de l’intervalle QT et la présence de l’anti-Ro/SSA a été démontrée (rapports de cotes ajustés de 5.1 à 12.6) et les patients porteurs de l’anti-Ro/SSA pourraient donc bénéficier de dépistage électrocardiographique systématique. Les points faibles et forts de cet article sont discutés dans le quatrième chapitre et des perspectives de recherches futures sont finalement abordées.

Incidencia de fibrilación auricular en las primeras 72 horas del post operatorio de revascularización miocárdica

Determinar la incidencia de fibrilación auricular en las primeras 72 horas del post operatorio en pacientes llevados a revascularización miocárdica utilizando dos técnicas de anestésia una convencional (AC) con anestésicos inhalados y opioides y otra con dexmedetomidina (AD.). cohorte retrospectivo, en donde se seleccionarán dos grupos de estudio, un grupo de expuestos, pacientes llevados a revascularización miocárdica con utilización técnica anestésica convencional y un grupo de no expuestos pacientes llevados a revascularización miocárdica con uso de dexmedetomidina como técnica de anestesia; A estos grupos se les hizo seguimiento por 72 horas para determinar la presencia de fibrilación auricular y la terapéutica instaurada.

Isquemia silenciosa e arritmias ventriculares são preditores independentes de evenos no pós-infarto do miocárdio de baixo risco

pós-infarto agudo do miocárdio (IAM) têm mostrado baixo valor preditivo positivo quando estudados isoladamente. A possibilidade da Eletrocardiografia Dinâmica de 24 horas (ECGD) fornecer dados referentes a isquemia silenciosa (IS), arritmias ventriculares e modulação autonômica do coração pelo estudo da variabilidade da freqüência cardíaca (VFC), levou o autor a empregar este método em pacientes acometidos de IAM com o objetivo de avaliar se estas três variáveis estariam relacionadas a presença de eventos desfavoráveis em evolução a médio prazo. Material e Métodos – Foram selecionados 91 pacientes acometidos de um primeiro IAM não-complicado e realizados exames de ECGD de 24 h por dois dias consecutivos, antes da alta hospitalar. Os parâmetros pesquisados nos exames foram: isquemia silenciosa, identificação e quantificação de arritmias ventriculares e determinação dos índices de VFC pelos métodos do domínio do tempo e do mapa de retorno tridimensional. Foram considerados como desfechos: re-infarto, angina instável, taquicardia ventricular sustentada e morte. Resultados – No seguimento médio de 27,7 meses (DP=15,45), 23 (25%) dos pacientes apresentaram eventos, sendo nove fatais. Os eventos foram mais freqüentes entre os pacientes que apresentaram extra-sístoles ventriculares ≥10/hora (p=0,01) e também naqueles com IS (p=0,02). Em modelo de análise multifatorial, a presença de dislipidemia elevou o valor preditivo positivo dessas variáveis. Nenhum dos índices de VFC esteve significativamente relacionado ao surgimento de eventos. Conclusões – Em pacientes pós-IAM de baixo risco, a presença de arritmias ventriculares freqüentes ou de isquemia silenciosa está relacionada a um prognóstico desfavorável. O estudo da VFC não mostrou utilidade na estratificação de risco destes pacientes.

High-resolution electrocardiography in dogs under doxorubicin-induced cardiomyopathy

Determinaram-se a ocorrência de potencial tardio em cães com cardiomiopatia induzida pela doxorrubicina e sua relação com o desenvolvimento de arritmias ventriculares ou morte súbita. Sete cães adultos, sem raça definida, de ambos os sexos foram utilizados. A cardiomiopatia foi induzida por infusão venosa lenta de doxorrubicina (30mg/m²) em intervalos de 21 dias, até uma dose total cumulativa de 240mg/m². Os animais foram monitorados ecocardiograficamente. Após a confirmação da cardiomiopatia, foi feito o registro da eletrocardiografia de alta resolução. Potenciais tardios foram observados em dois animais que morreram subitamente poucos dias após.

Holter electrocardiography in dogs showing doxorubicin-induced dilated cardiomyopathy

O estudo consistiu na identificação precoce da ocorrência de arritmias em cães com cardiomiopatia dilatada experimental induzida pela doxorrubicina (DOX). Utilizaram-se 10 cães adultos, sadios, distribuídos nos grupos A (n=5) e B (n=5). O grupo B recebeu 30mg/m² de DOX, via intravenosa, a cada 21 dias, até a dose cumulativa de 180 ou 240mg/m². No grupo A (controle), administrou-se solução salina 0,9%, via intravenosa, nos mesmos intervalos do grupo B. Ao se evidenciar o quadro de disfunção miocárdica nos cães do grupo B, caracterizado pela fração de encurtamento menor que 20%, aumento da separação septal do ponto E acima de 0,7cm e aumento do índice volumétrico do ventrículo esquerdo ao final da sístole (61,4ml/m²), realizaram-se os eletrocardiogramas por 24 horas. Os resultados demonstraram aumentos de 44,6% e 41,7% nas freqüências cardíacas mínima e média, respectivamente, e presença, com maior freqüência, de arritmias supraventriculares do que ventriculares nos animais do grupo B. Concluiu-se que o Holter é eficaz e demonstra, com precocidade e melhor definição, as alterações da freqüência e do ritmo cardíaco de cães com disfunção miocárdica induzida pela doxorrubicina.

Some cardiopulmonary effects of sevoflurane in crested caracara (Caracara plancus)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Calcium gluconate and sodium succinate for therapy of sodium fluoroacetate experimental intoxication in cats: clinical and electrocardiographic evaluation

Sodium fluoroacetate (SFAC) or Compound 1080 is a potent rodenticide, largely used after 1946 for rodent and home pest control. The toxic effects of SFAC are caused by fluorocitrate action, a toxic metabolite, which has a competitive action with aconitase enzyme, leading to citrate accumulation and resulting in interference in energy production by Krebs cycle blockade. In the present study, domestic cats were intoxicated with oral doses of fluoroacetate (0.45 mg/kg). The intoxicated animals presented emesis, diarrhea with abdominal pain posture and an abdominal palpation, tachypnea, bilateral midriasis, hypothermia, hyperexcitability and convulsions. Blood gas analysis indicated decreased pH and bicarbonate levels. Serum ionized calcium was also decreased. ECG showed non-specific changes in ventricular repolarization and ventricular arrhythmias. The survival rate was 75% in the treated group with calcium gluconate and sodium succinate and 37.5% in the non-treated group.

Effects of the opiold remifentanil on the arrhythmogenicity of epinephrine in halothane-anesthetized dogs

Opioids may exert a protective effect against ventricular arrhythmias via a vagally mediated mechanism. This study evaluated the effects of the opioid remifentanil on arrhythmogenicity of epinephrine during halothane anesthesia. Eight dogs were assigned to 2 treatments in a randomized crossover design, with 1-week intervals between treatments. Anesthesia was maintained with 1.3% end-tidal halothane in oxygen and mechanical ventilation to maintain eucapnia. A constant rate infusion of remifentanil (0.72 mu g/kg/min) was administered throughout the study in the experimental treatment, while control animals received physiologic saline as placebo. The arrhythmogenic dose of epinephrine (ADE), defined as 4 premature ventricular complexes (PVCs) within 15 s, was determined by administering progressively increasing infusion rates of epinephrine (2.5, 5.0, and 10 mu g/kg/min), allowing 20 min intervals between each infusion rate. In both treatments, epinephrine infusions induced bradyarrhythmias and atrioventricular conduction disturbances, which were followed by escape beats and PVCs. In the remifentanil treatment, mean s ADE values (11.3 +/- 4.9 mu g/kg) did not differ from values observed in control animals (9.9 +/- 6.1 mu g/kg). on the basis of the ADE model for assessing the arrhythmogenity of drugs during halothane anesthesia, the present study did not demonstrate a protective effect of remifentanil (0.72 mu g/kg/min) against ventricular arrhythmias in dogs.

Clinical and electrocardiographic evaluation during experimental toad poisoning in dogs

Accidents involving toad poisoning are frequent and dogs are the most common victims; they become poisoned by biting or ingesting a toad. When released in the organism, the venom is absorbed by both the oral mucosa and the digestive tract, initiating its toxic action. The aim of this work was to evaluate the clinical and electrocardiographic aspects of dogs subjected to experimental toad poisoning, as well as their response to treatment with propranolol. Twenty dogs were divided into two groups, a control group (n = 5) and a poisoned group (n = 15). After general anesthesia, the control group received a placebo, while the poisoned group received a venom aliquot through an orogastric tube. Results were tested through multivariate analysis (p < 0.05). The animals in the poisoned group had gastrointestinal symptoms including emesis, intense salivation, hyperemic or congested oral mucosa and pasty diarrhea. Non-responsive mydriasis, nystagmus, depression, stupor, tachypnea, opisthotonus and ataxia were also manifested by 100% of the poisoned animals. Affected dogs had an increase in blood pressure, statistically significant throughout study. Five poisoned animals developed ventricular tachycardia and were treated with propranolol (0.5 mg/kg IV). All propranolol-treated animals returned to normal sinus rhythm, which evidences the efficacy of this drug to treat ventricular arrhythmias caused by toad venom.

Ação antiarrítmica do isofluorano em cães submetidos à arritmias ventriculares induzidas por cloreto de bário

Avaliou-se a ação antiarrítmica do isofluorano em cães submetidos a arritmias ventriculares pelo uso de cloreto de bário, utilizando-se de seis cães, machos e fêmeas, que receberam uma dose de 3mg/kg de peso IV de cloreto de bário a 2,5% (G1). O mesmo protocolo foi repetido, nos mesmos animais, sob anestesia geral com isofluorano (G2). Usou-se a eletrocardiografia computadorizada para avaliar o ritmo cardíaco, a duração e/ou amplitude das ondas e os intervalos eletrocardiográficos. Não se verificou alteração no ritmo cardíaco em G2, diferente de G1, que apresentou freqüentes arritmias ventriculares na forma de bigeminismo e taquicardia ventricular multifocal. Houve diferença significativa entre os grupos em relação à freqüência cardíaca nos minutos iniciais de observação, quando ocorreu aumento na freqüência cardíaca em G1. A utilização do isofluorano conferiu ação antiarrítmica em cães com arritmias induzidas pelo cloreto de bário, reforçando suas indicações a pacientes com risco considerável de desenvolvimento de arritmias ventriculares.

Efeitos da obesidade e do sobrepeso sobre parâmetros cardiovasculares e respiratórios em gatos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Variabilidade da frequência cardíaca em cães com degeneração mixomatosa crônica da valva mitral

Pós-graduação em Medicina Veterinária - FCAV

Rilascio dei biomarkers di danno miocardico dopo iniezione diretta per via percutanea di cellule staminali e terapia genica

Aims: We aimed to quantify the release of bio-markers of myocardial damage in relation to direct intramyocardial injections of genes and stem cells in patients with severe coronary artery disease. Methods and Results: We studied 71 patients with “no-option” coronary artery disease. Patients had, via the percutaneous transluminal route, a total of 11±1 (mean ± SD) intramyocardial injections of vascular endothelial growth factor genes (n=56) or mesenchymal stromal cells (n=15). Injections were guided to an ischemic area by electromechanical mapping, using the NOGA™/Myostar™ catheter system. ECG was monitored continuously until discharge. Plasma CKMB (upper normal laboratory limit=5 μg/l) was 2 μg/l (2-3) at baseline; increased to 6 (5-9) after 8 hours (p < 0.0001) and normalized to 4 (3-5) after 24 hours. A total of 8 patients (17%), receiving a volume of 0.3 ml per injection, had CKMB rises exceeding 3 times the upper limit, whereas no patient in the group receiving 0.2 ml had a more than two fold CKMB increase. No patient developed new ECG changes. There were no clinically important ventricular arrhythmias and no death. Conclusion: Direct Intramyocardial injections of stem cells or genes lead to measurable release of cardiac bio-markers, which was related to the injected volume.

A Phase Space Box-counting based Method for Arrhythmia Prediction from Electrocardiogram Time Series

Arrhythmia is one kind of cardiovascular diseases that give rise to the number of deaths and potentially yields immedicable danger. Arrhythmia is a life threatening condition originating from disorganized propagation of electrical signals in heart resulting in desynchronization among different chambers of the heart. Fundamentally, the synchronization process means that the phase relationship of electrical activities between the chambers remains coherent, maintaining a constant phase difference over time. If desynchronization occurs due to arrhythmia, the coherent phase relationship breaks down resulting in chaotic rhythm affecting the regular pumping mechanism of heart. This phenomenon was explored by using the phase space reconstruction technique which is a standard analysis technique of time series data generated from nonlinear dynamical system. In this project a novel index is presented for predicting the onset of ventricular arrhythmias. Analysis of continuously captured long-term ECG data recordings was conducted up to the onset of arrhythmia by the phase space reconstruction method, obtaining 2-dimensional images, analysed by the box counting method. The method was tested using the ECG data set of three different kinds including normal (NR), Ventricular Tachycardia (VT), Ventricular Fibrillation (VF), extracted from the Physionet ECG database. Statistical measures like mean (μ), standard deviation (σ) and coefficient of variation (σ/μ) for the box-counting in phase space diagrams are derived for a sliding window of 10 beats of ECG signal. From the results of these statistical analyses, a threshold was derived as an upper bound of Coefficient of Variation (CV) for box-counting of ECG phase portraits which is capable of reliably predicting the impeding arrhythmia long before its actual occurrence. As future work of research, it was planned to validate this prediction tool over a wider population of patients affected by different kind of arrhythmia, like atrial fibrillation, bundle and brunch block, and set different thresholds for them, in order to confirm its clinical applicability.