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The cellular pathophysiology of myocardial hypertrophyWallis, William Richard James January 1997 (has links)
No description available.
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Phenotypic heterogeneity in the Romano-Ward syndromeCross, Stephen January 1994 (has links)
The Romano-Ward syndrome is a familial disorder inherited as an autosomal dominant trait, the gene of which has been linked to the HLA locus on chromosome 6 or the Harvey-ras oncogene on chromosome 11. The genetic linkage, left and right ventricular function, and the integrity of the baroreflex were studied in subjects from two unrelated families with this condition. Neither family showed genetic linkage to either the HLA locus or to the Harvey-ras gene. Blood pool tomography was used to assess left and right ventricular function: left ventricular wall motion abnormalities were seen only in one family; the degree of dysfunction was related to the presence of symptoms. Minor disturbances of right ventricular function were seen in some subjects from both families, but did not correlate to the presence nor to the severity of symptoms. Using 14 frequencies of cyclical neck suction, the frequency response of the carotid baroreceptor heart-rate reflex was studied. One family had essentially a normal baroreflex. However, all members of the other family had similarly abnormal responses: a higher sensitivity at high and low suction frequencies, suggesting abnormalities of parasympathetic and sympathetic tone respectively. The Romano-Ward syndrome is a heterogeneous disorder: differences in genetic linkage (compared with historical controls), left ventricular function, and baroreflex sensitivity have been demonstrated.
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Úloha sukcinátu v ischemické toleranci srdce potkanů / The role of succinic acid in cardiac ischemic tolerance in ratsKordač, Petr January 2021 (has links)
Succinate is one of the intermediate in the Krebs cycle, which in recent years has been shown to interfere with other cellular events, some of which may affect cardiac ischemic tolerance. The aim of this project was to clarify its cardioprotective role in rat hearts subjected to acute ischemia-reperfusion. The myocardial resistance to acute ischemia (infarct size and incidence and severity of ischemic and reperfusion arrhythmias) was analyzed using the Langendorff method of isolated perfused heart at a constant flow with acute succinate administration. Local ischemia was induced by ligation of left anterior descending coronary artery. Acute administration of 1 mM succinate before 60 minutes of ischemia or before reperfusion only had a beneficial effect on reducing the infarct size by 25-30 % compared to the control group. At the same time, it had an adverse effect on the incidence and severity of ischemic and reperfusion arrhythmias. Key words: Succinate, heart, rat, heart-attack, ventricular arrhythmias
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Estudo do eletrocardiograma ambulatorial, eletrocardiograma de alta resolução (ECGAR) e variabilidade da frequência cardíaca como indicadores prognósticos na cardiomiopatia arritmogênica de cães Boxer / Study of ambulatory electrocardiography, signal-averaged electrocardiogram and heart rate variability as prognostic factors in Boxer dogs with arrhythmogenic cardiomyopathyChamas, Patrícia Pereira Costa 31 January 2011 (has links)
A cardiomiopatia arritmogênica do ventrículo direito (CAVD) é uma doença miocárdica genética e hereditária, com alta prevalência entre os cães da raça Boxer, causada por alterações nos genes que codificam os receptores de rianodina ou os desmossomos cardíacos. Caracteriza-se, histologicamente, por atrofia de miócitos do ventrículo direito, principalmente, com reposição por tecido adiposo e fibroso. Tais lesões causam instabilidade elétrica do miocárdio, com consequente aparecimento de arritmias ventriculares por re-entrada. Os animais afetados podem apresentar-se assintomáticos ou com frequentes episódios de síncope ou morte súbita; ainda, podem desenvolver uma forma mais grave da doença, com dilatação ventricular e disfunção sistólica, evoluindo para insuficiência cardíaca congestiva. Devido à escassez de estudos determinando fatores preditivos para a ocorrência de morte de origem cardíaca nestes animais, o presente estudo objetivou avaliar o valor prognóstico das variáveis de eletrocardiografia ambulatorial (Holter), eletrocardiografia de alta resolução (ECGAR) e variabilidade de frequência cardíaca (VFC) na CAVD do Boxer. Para tanto, tais parâmetros foram avaliados em 92 cães, distribuídos de acordo com a raça ou o estágio da doença em cinco grupos: cãescontrole da raça Pastor Alemão (grupo PA), cães-controle da raça Boxer (grupo BC), cães Boxer suspeitos para CAVD (grupo BSUS), cães Boxer afetados pela CAVD (grupo BCAVD) e cães Boxer com CAVD e disfunção sistólica (grupo BDS). Foram encontrados potenciais tardios ao ECGAR em poucos cães do grupo CAVD (21,05%); no entanto, dentre os cães do grupo BDS este percentual foi bem mais expressivo (83,33%), demonstrando que a sensibilidade deste exame é maior em estágios mais avançados da doença. Apesar da observação destes potenciais tardios, as variáveis analisadas ao ECGAR não apresentaram correlação com a sobrevida dos cães com CAVD. Também não se constituíram em fatores preditivos de morte os índices de VFC. Apenas a idade do animal no momento do diagnóstico, a ocorrência de taquicardia ventricular não sustentada e de extrassístoles supraventriculares ao Holter apresentaram-se como fatores prognósticos na sobrevida dos cães Boxer com CAVD. As variáveis de ECGAR e VFC não evidenciaram correlação com o número ou grau das arritmias ventriculares registradas ao Holter dos cães Boxer com CAVD, demonstrando que a gênese destas arritmias não está relacionada à disfunção do sistema nervoso simpático. / Arhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic and hereditary myocardial disease with a high prevalence among Boxer dogs, caused by changes in genes that encode ryanodine receptors or desmosomes. It is characterized histologically by myocyte atrophy, especially of the right ventricle, with replacement by fat and fibrous tissue. Such injuries cause electrical instability of myocardium, with subsequent appearance of re-entrant ventricular arrhythmias. Affected animals may be asymptomatic, show frequent episodes of syncope or sudden death, or develop a more severe form of disease with ventricular dilatation and systolic dysfunction, progressing to congestive heart failure. Given the paucity of studies determining preditive factors for the occurrence of cardiac death in these animals, this study aimed to evaluate the prognostic value of variables of ambulatory electrocardiography (Holter) signal-averaged electrocardiography (SAECG) and heart rate variability (HRV) in Boxer dogs with ARVC. For this, these parameters were evaluated in 92 dogs, divided according to race or stage of the disease into five groups: German Shepherd control dogs (group PA), Boxer control dogs (group BC), Boxer dogs suspicious for ARVC (group BSUS), Boxer dogs affected by ARVC (group BCAVD) and Boxer dogs with ARVC and systolic dysfunction (group BDS). Late potentials were found in SAECG of few dogs on group CAVD (21.05%), however, among dogs of group BDS, this percentage was much higher (83.33%), demonstrating that the sensitivity of this test is higher in more advanced stages of the disease. Despite the observation of late potentials in SAECG, the variables of this test were not correlated with survival in dogs with ARVC. The indexes of HRV were also not significantly predictive of death in ARVC dogs. Only the age of the animal at diagnosis, the occurrence of nonsustained ventricular tachycardia and supraventricular ectopic beats on Holter presented as prognostic factors in survival of Boxer dogs with ARVC. The SAECG and HRV variables were not correlated with the number or degree of ventricular arrhythmias recorded by Holter of ARVC Boxer dogs, demonstrating that the genesis of these arrhythmias is not related to dysfunction of the sympathetic nervous system.
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Estudo do eletrocardiograma ambulatorial, eletrocardiograma de alta resolução (ECGAR) e variabilidade da frequência cardíaca como indicadores prognósticos na cardiomiopatia arritmogênica de cães Boxer / Study of ambulatory electrocardiography, signal-averaged electrocardiogram and heart rate variability as prognostic factors in Boxer dogs with arrhythmogenic cardiomyopathyPatrícia Pereira Costa Chamas 31 January 2011 (has links)
A cardiomiopatia arritmogênica do ventrículo direito (CAVD) é uma doença miocárdica genética e hereditária, com alta prevalência entre os cães da raça Boxer, causada por alterações nos genes que codificam os receptores de rianodina ou os desmossomos cardíacos. Caracteriza-se, histologicamente, por atrofia de miócitos do ventrículo direito, principalmente, com reposição por tecido adiposo e fibroso. Tais lesões causam instabilidade elétrica do miocárdio, com consequente aparecimento de arritmias ventriculares por re-entrada. Os animais afetados podem apresentar-se assintomáticos ou com frequentes episódios de síncope ou morte súbita; ainda, podem desenvolver uma forma mais grave da doença, com dilatação ventricular e disfunção sistólica, evoluindo para insuficiência cardíaca congestiva. Devido à escassez de estudos determinando fatores preditivos para a ocorrência de morte de origem cardíaca nestes animais, o presente estudo objetivou avaliar o valor prognóstico das variáveis de eletrocardiografia ambulatorial (Holter), eletrocardiografia de alta resolução (ECGAR) e variabilidade de frequência cardíaca (VFC) na CAVD do Boxer. Para tanto, tais parâmetros foram avaliados em 92 cães, distribuídos de acordo com a raça ou o estágio da doença em cinco grupos: cãescontrole da raça Pastor Alemão (grupo PA), cães-controle da raça Boxer (grupo BC), cães Boxer suspeitos para CAVD (grupo BSUS), cães Boxer afetados pela CAVD (grupo BCAVD) e cães Boxer com CAVD e disfunção sistólica (grupo BDS). Foram encontrados potenciais tardios ao ECGAR em poucos cães do grupo CAVD (21,05%); no entanto, dentre os cães do grupo BDS este percentual foi bem mais expressivo (83,33%), demonstrando que a sensibilidade deste exame é maior em estágios mais avançados da doença. Apesar da observação destes potenciais tardios, as variáveis analisadas ao ECGAR não apresentaram correlação com a sobrevida dos cães com CAVD. Também não se constituíram em fatores preditivos de morte os índices de VFC. Apenas a idade do animal no momento do diagnóstico, a ocorrência de taquicardia ventricular não sustentada e de extrassístoles supraventriculares ao Holter apresentaram-se como fatores prognósticos na sobrevida dos cães Boxer com CAVD. As variáveis de ECGAR e VFC não evidenciaram correlação com o número ou grau das arritmias ventriculares registradas ao Holter dos cães Boxer com CAVD, demonstrando que a gênese destas arritmias não está relacionada à disfunção do sistema nervoso simpático. / Arhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic and hereditary myocardial disease with a high prevalence among Boxer dogs, caused by changes in genes that encode ryanodine receptors or desmosomes. It is characterized histologically by myocyte atrophy, especially of the right ventricle, with replacement by fat and fibrous tissue. Such injuries cause electrical instability of myocardium, with subsequent appearance of re-entrant ventricular arrhythmias. Affected animals may be asymptomatic, show frequent episodes of syncope or sudden death, or develop a more severe form of disease with ventricular dilatation and systolic dysfunction, progressing to congestive heart failure. Given the paucity of studies determining preditive factors for the occurrence of cardiac death in these animals, this study aimed to evaluate the prognostic value of variables of ambulatory electrocardiography (Holter) signal-averaged electrocardiography (SAECG) and heart rate variability (HRV) in Boxer dogs with ARVC. For this, these parameters were evaluated in 92 dogs, divided according to race or stage of the disease into five groups: German Shepherd control dogs (group PA), Boxer control dogs (group BC), Boxer dogs suspicious for ARVC (group BSUS), Boxer dogs affected by ARVC (group BCAVD) and Boxer dogs with ARVC and systolic dysfunction (group BDS). Late potentials were found in SAECG of few dogs on group CAVD (21.05%), however, among dogs of group BDS, this percentage was much higher (83.33%), demonstrating that the sensitivity of this test is higher in more advanced stages of the disease. Despite the observation of late potentials in SAECG, the variables of this test were not correlated with survival in dogs with ARVC. The indexes of HRV were also not significantly predictive of death in ARVC dogs. Only the age of the animal at diagnosis, the occurrence of nonsustained ventricular tachycardia and supraventricular ectopic beats on Holter presented as prognostic factors in survival of Boxer dogs with ARVC. The SAECG and HRV variables were not correlated with the number or degree of ventricular arrhythmias recorded by Holter of ARVC Boxer dogs, demonstrating that the genesis of these arrhythmias is not related to dysfunction of the sympathetic nervous system.
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Athletes' heart and exercise related sudden cardiac death : across the age spanWilson, Mathew January 2010 (has links)
Background - Regular exercise reduces the risk of cardiovascular disease and subsequent sudden cardiac death (SCD). However, a small, but notable proportion of athletes die suddenly due to inherited or congenital disorders of the heart that predispose to malignant ventricular arrhythmias. Such tragedies are highly publicised, particularly when high-profile athletes are involved. To date, limited evidence for the efficacy of cardiovascular pre-participation screening exists outside of the Italian experience. Furthermore, limited data exists examining the impact of ethnicity on cardiac adaptations to physical training. Whilst the cardiovascular benefits of exercise are well known, the impact of life-long endurance exercise is less well understood. Long term high-intensity endurance exercise is associated with changes in cardiac morphology together with electrocardiographic alterations that are believed to be physiologic in nature. Recent data however, has suggested a number of deleterious adaptive changes in cardiac structure, function and electrical activity in response to life-long endurance activity. Aims and Objectives - The aims of this PhD were; 1) To find an effective preparticipation screening method that would successfully identify pre-existing cardiovascular abnormalities, 2) To identify the prevalence of hypertrophic cardiomyopathy and Long QT syndrome in elite UK athletes; 3) To examine the impact and significance of ethnicity upon left ventricular remodelling in elite athletes, and 4) To examine the acute and chronic impact of ultra-endurance exercise across the life-span in male endurance athletes. Major Results and Conclusions – 1) Study 2 sought to confirm the efficacy of resting 12-Lead ECG ‘alongside’ personal/family history questionnaires and physical examinations as collective tools to identify diseases that have the potential of causing sudden death within a cohort of elite junior athletes (n=1074) and physically active school children (n=1646). Nine participants were identified with a positive diagnosis of a disease associated with SCD. None of those diagnosed with a disease associated with SCD were symptomatic or had a family history of note. Thus, personal symptoms and family history questionnaires alone are inadequate in the identification of individuals with diseases associated with SCD. In conclusion, resting 12-Lead ECG is paramount when screening for diseases that have the potential of causing sudden death in the young. 2) Study 3 examined 3,500 asymptomatic elite athletes (75% male) with a mean age of 20.5 ± 5.8 years with 12-lead ECG and 2-dimensional echocardiography. None had a known family history of HCM. Of the 3,500 athletes, 53 (1.5%) had LVH (mean 13.6 ± 0.9mm, range 13 to 16mm), and of these 50 had a dilated LV cavity with normal diastolic function to indicate physiological left ventricular hypertrophy. Three (0.08%) athletes with LVH had a non-dilated LV cavity and associated deep T-wave inversion that could have been consistent with HCM. However, none of the 3 athletes had any other phenotypic features of HCM on further non-invasive testing and none had first-degree relatives with features of HCM. In conclusion, the prevalence of HCM in elite athletes is significantly less than in the general population; with the demands of strenuous exercise on the cardiovascular system selecting out most individuals with HCM. Study 4 examined 2000 elite athletes in order to identify the prevalence of Long QT syndrome. Three athletes had a QTc value of >500 ms and all exhibited one of: paradoxical prolongation of QTc during exercise, a confirmatory genetic mutation, or prolonged QTc in a first-degree relative. In contrast, none of the athletes with a QTc value of <500 ms had any other features to indicate LQTS. Accordingly, the prevalence of a prolonged QTc interval in elite British athletes is 0.4%. 3) Study 6 examined 300 nationally ranked UK black male athletes (mean age 20.5 years) in comparison to 150 black and white sedentary individuals and 300 highly-trained white male athletes. Black athletes exhibited greater LV wall thickness and cavity size compared with sedentary black and white individuals. Black athletes had greater LV wall thickness compared with white athletes. A minority of black athlete’s exhibit LVH ≥15 mm; proposing that in the absence of cardiac symptoms or a family history of HCM, an LV wall thickness ≥15 mm in black athletes may represent physiologic LVH when the LV cavity is enlarged and diastolic indexes are normal. 7 black athletes (12%) with LVH displaying deep T-wave inversions in leads V1 to V4. In conclusion, in the absence of obvious pathology, these electrical anomalies in black athletes likely represent a normal spectrum of ECG changes in response to physical training. 4) Study 8 examined 17 male participants (age 33.5 ± 6.5 years, 26–40 years) using cardiac magnetic resonance (CMR) and echocardiography before and after a marathon to investigate the relationship between systolic function and diastolic function against biomarkers of cardiac damage. Results demonstrates biomarkers of myocardial cell damage following an acute bout of prolonged exercise are not associated with either systolic or diastolic functional measures, and do not seem to be associated with any detectable myocardial inflammation, oedema, or scarring using either gold standard techniques of gadolinium enhanced CMR or echocardiography respectively. The impact of multiple episodes of prolonged exercise, as experienced by highly trained veteran endurance athlete is not fully understood. 5) Study 10 examined the cardiac structure and function of 12 life-long, competitive endurance veteran athletes (> 50 yrs, mean ± SD marathons 178 ± 209 (range 20 – 650)) against 17 young male endurance athletes (<40 yrs) using echocardiography and CMR with late gadolinium enhancement (LGE) to assess myocardial fibrosis. Lifelong veteran athletes had smaller LV and RV end-diastolic and end-systolic volumes (p<0.05) but maintained LV and RV systolic function compared with young athletes. In 6 (50%) of the veteran athletes LGE of CMR indicated the presence of myocardial fibrosis; no LGE in the young athletes. The prevalence of LGE in veteran athletes was not associated with the number of competitive marathons or ultra-endurance marathons (>50 miles) completed, age, LV and RV end-diastolic volumes or LV mass (p>0.05). In conclusion, there is limited evidence at present demonstrating that cardiovascular re-modelling following lifelong endurance exercise leads to long-term disease progression, cardiovascular disability or SCD.
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Vliv časného postnatálního období na rozvoj pro-arytmogenního substrátu po tlakovém přetížení srdce potkana / Impact of early postnatal period on pro-arrhytmogenic substrate development caused by pressure overload in rat heartZábrodská, Eva January 2021 (has links)
In adult heart, pressure overload leads to cardiac hypertrophy. Higher propensity of hypertrophied myocardium to life-threatening arrhythmia is attributed to structural, mechanical and electrical remodeling. Pro-arrhythmogenic remodeling comprise several factors depending on an experimental model and a stage of heart failure. This thesis aims to characterize the impact of these factors in our unique model of pressure overloaded neonatal rat heart. The constriction of abdominal aorta was performed at postnatal day 2 in male Wistar rats. Decreased body weight, significant since week 6, was observed during development of cardiomegaly. At 12 weeks, the heart to body weight ratio was increased by 45 % and by 109 % in group with compensated (AC I) and decompensated (AC II) heart failure, respectively. At this age, the ECG was recorded and histological and immunohistochemical measurements were performed to analyze the pro-arrhythmogenic remodeling of working myocardium and cardiac conduction system. The markers of pro-arrhytmogenic remodeling such as significant prolongation of QT and QTc intervals were observed in the ECG recordings of AC II animals. However, spontaneously occurring arrhythmias was not detected. Further analysis of working myocardium showed decrease in Cx43 expression and its...
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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 grasAubin, Marie-Claude 04 1900 (has links)
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. / Knowledge is insufficient regarding cardiovascular modifications occurring prior to the development of overt obesity and dyslipidemia. In this regard, the present project aimed at testing the hypothesis stipulating that the administration of a high fat diet for an 8-week period in female rats can adversely influence cardiac function and remodeling prior to the development of overt obesity, and in the absence of hyperlipidemia and hyperglycaemia.
To directly examine these issues, normal female Sprague-Dawley rats were fed a standard (SD; 12.5% lipid, kcal) or a high-fat diet (HF; 42% lipids, kcal) for 8 weeks. This regimen was insufficient to induce a significant gain in body mass in HF rats (329±14g) as compared to SD rats (300±10g), or any variation in the lipid profile. By contrast, systemic arterial hypertension developed in high fat fed rats (130±4mmHg versus SD, 108±6mmHg, p<0.05), additionally to a significant decrease in acetylcholine-mediated maximal relaxation of isolated aortic rings (HF, 22±5%) compared to rats fed a standard diet (53±8%, p<0.05). Chronic oral administration of the antioxidant resveratrol (RES; 20 mg·kg-1·d-1) prevented the development of both pathological alterations, attesting to the implication of oxidative stress. However, it failed to attenuate the perivascular fibrosis that developed following the administration of the high-fat diet.
Following ischemia/reperfusion injury, scar length (SD, 0.29±0.09 versus HF, 0.32±0.13 cm), thickness (SD, 0.05±0.02 versus HF, 0.06±0.01 cm) and collagen α1 type 1 content (SD, 0.21±0.04 versus HF, 0.20±0.04 arbitrary units/mm2) in the infarcted heart of rats fed a high fat diet were similar to infarcted normal rats. Despite these findings, the rate of death was significantly increased (p<0.05) in female rats fed a high fat diet (56%) compared to rats fed a standard diet (5%). An electrophysiology approach revealed that normal female rats fed a high fat diet had an increased incidence (p<0.05) of induced ventricular extrasystoles. In addition, these hearts presented a functional sympathetic hyperinnervation, as reflected by the increased density of neurofilament-M immunoreactive fibres (SD, 2020±260 versus HF, 2830±250 μm2/mm2; p<0.05) and increased protein expression of tyrosine hydroxylase. The gap junction function was also impaired,
characterized by lateralization and internalization of connexine 43, and a decreased expression of connexine 40 in intercalated discs of rats fed a high fat diet.
Thus, prior to the development of overt obesity and dyslipidemia, female rats with
modest hypertension exhibit an arrhythmogenic cardiac phenotype due in part to sympathetic hyperinnervation and a concomitant aberrant pattern of gap junctional protein expression and distribution. The lack of significant clinical manifestations of obesity in the present study does not enable clinicians to suspect the increased susceptibility to ventricular arrhythmias. Hence, in presence of modest hypertension in a non-obese patient, evaluation of the sympathetic activity by the assessment of circulating catecholamine could be helpful in detecting patients at high risk for sudden death.
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Dysfonction cardiovasculaire et arythmies ventriculaires de l’ischémie-reperfusion : effets délétères de l’hypoxie intermittente et protecteurs de la supplémentation en zinc / Cardiovascular dysfunction and ventricular arrhythmias associated with ischemia-reperfusion : deleterious effect of intermittent hypoxia and protective effects of zinc supplementationMorand, Jessica 31 March 2017 (has links)
Le syndrome d’apnées obstructives du sommeil (SAOS) est associé à une forte morbi-mortalité cardiovasculaire. L’hypoxie intermittente (HI), conséquence majeure des apnées, est à l’origine d’un stress oxydant, d’une activation de HIF-1 (hypoxia inducible factor 1) et d’une expression d’endothéline (ET-1), tous impliqués dans les complications cardiovasculaires liées à l’HI.Dans un premier temps, nous avons démontré que l’HI augmentait l’incidence des arythmies ventriculaires létales associées à l’ischémie myocardique. Parmi les mécanismes potentiels impliqués, l’analyse spectrale de la variabilité de la fréquence cardiaque et de la pression artérielle et le dosage des catécholamines ont mis en évidence une activation sympathique chez les animaux exposés à l’HI. L’HI est également à l’origine d’altérations de la repolarisation ventriculaire (allongement du QTc et du Tpeak-Tend) et d’une dispersion du gradient transmural (allongement de la durée du potentiel d’action endocardique) associées à une augmentation de l’expression de canaux calciques de type LTCC et TRPC dans l’endocarde.Dans la seconde partie de ce travail de thèse, nous nous sommes intéressés aux perturbations de l’homéostasie du zinc en réponse au stress oxydant causé par l’ischémie-reperfusion (IR) ou par l’HI et aux propriétés cardioprotectives de la supplémentation en zinc dans ce contexte. Nous avons montré que l’IR et l’HI induisaient une diminution des concentrations de zinc myocardiques et plasmatiques, respectivement. Nous avons mis en évidence les effets bénéfiques de la supplémentation en zinc vis-à-vis des arythmies ventriculaires et des altérations myocardiques induites par l’IR. L’administration de zinc lors de la reperfusion a également permis d’abolir l’augmentation de la taille d’infarctus induite par l’exposition chronique à l’HI.Finalement, nous avons étudié les effets de la déplétion en zinc sur des cellules endothéliales à l’aide d’un chélateur spécifique du zinc, le TPEN. Nous avons observé que l’exposition des cellules au TPEN entraînait une translocation nucléaire de HIF-1α et une augmentation de la sécrétion d’ET-1 avec, comme conséquence, une augmentation de la capacité migratoire des cellules endothéliales. Ainsi, une déplétion en zinc semble conduire à une activation de l’axe HIF-1-ET-1 connu pour ses effets délétères lors de l’HI.En résumé, l’exposition chronique à l’HI exacerbe les arythmies et augmente la taille d’infarctus lors de l’IR. L’activation sympathique, le stress oxydant et l’altération de l’homéostasie du zinc pourraient être impliqués. L’utilisation d’outils pharmacologiques permettrait de confirmer leur rôle et potentiellement de prévenir les altérations cardiovasculaires liées à l’HI et au SAOS. / Obstructive sleep apnea (OSA) is associated with increased cardiovascular morbidity and mortality. Intermittent hypoxia (IH), one of the major consequences of apneas, leads to oxidative stress, activation of HIF-1 (hypoxia inducible factor 1) and endothelin (ET-1) expression, all known to play an important role in the cardiovascular consequences of OSA.First, we have demonstrated that IH increases the incidence of ischemia-related lethal ventricular arrhythmias. Among the potential mechanisms involved, spectral analysis of heart rate and blood pressure variability and catecholamine assay, showed a sympathetic activation in animals exposed to IH. IH was also responsible for alterations in ventricular repolarisation (increased QTc and Tpeak-Tend intervals) and dispersion of the transmural gradient (increased endocardial action potential duration). These alterations were associated with increased expression of endocardial LTCC and TRPC calcium channels.The second part of the thesis aimed at investigating zinc homeostasis in response to the oxidative stress induced by ischemia-reperfusion (IR) or IH as well as the beneficial effects of zinc supplementation in this context. We observed that IR and IH induced a decrease in myocardial and plasma zinc concentrations, respectively. We also highlighted the protective effects of zinc supplementation during reperfusion against the ventricular arrhythmias and myocardial dysfunction induced by IR. Zinc administration during reperfusion also abolished the increase in infarct size induced by chronic IH exposure.Finally, we investigated the effects of zinc depletion in endothelial cells exposed to TPEN, a specific zinc chelator. We observed that TPEN induced a nuclear translocation of HIF-1α and an increase in ET-1 secretion with a resulting increase in endothelial cell migration. Thus, zinc depletion appears to promote activation of the HIF-1-ET-1 axis, known for its deleterious effects upon IH.In summary, chronic IH exposure enhances ventricular arrhythmias and increases infarct size upon myocardial I/R. Sympathetic activation, oxidative stress and alterations of zinc homeostasis appear to be contributing factors. Pharmacological targeting of these alterations should be performed in order to confirm their role as well as to potentially prevent the deleterious cardiovascular consequences of IH and OSA.
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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 grasAubin, Marie-Claude 04 1900 (has links)
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