Cardiomiopatia dilatada (CMD) é uma doença miocárdica caracterizada por dilatação cardíaca e redução da contratilidade da parede do ventrículo esquerdo ou de ambos os ventrículos, sendo a etiologia de origem genética ou desconhecida. Em suínos existem raros relatos de CMD, sendo frequentemente relacionados com intoxicações por ionóforos ou gossipol. Surtos de CMD de etiologia desconhecida em suínos de rebanhos comerciais no Brasil sugeriram a existência de nova etiologia, possivelmente nutricional. Este estudo teve como objetivo investigar as possíveis causas dos surtos de CMD em suínos, a partir de análises macroscópicas, microscópicas, bioquímicas, cromatográficas, moleculares, imuno-histoquímica (IHQ) e reprodução experimental. E teve como resultado 2 artigos científicos. O primeiro artigo descreve os achados clínicos, patológicos, químicos e toxicológicos de três surtos de CMD em suínos de crescimento, além da reprodução experimental desta condição utilizando a ração de uma das propriedades afetadas. Para o estudo experimental utilizou-se 9 animais divididos em 3 grupo; Grupo 1 recebendo ração suspeita, Grupo 2 metade ração suspeita mais metade de ração controle e o grupo 3 recebeu ração controle. Dois suínos do grupo 1 apresentaram condições clínicas e patológicas semelhantes aos casos naturais após 8 dias de consumo da ração suspeita. Os principais sinais clínicos observados eram tosse e dispneia grave. Na necropsia foram constatados dilatação cardíaca bilateral acentuada, hidrotórax, hidropericárdio, edema pulmonar, ascite e fígado com aspecto de noz moscada. O segundo artigo teve como objetivo fazer a caracterização histológica, histoquímica e imuno-histoquímica das lesões cardíacas em 8 suínos com CMD e compara-las com dois suínos controles. As principais lesões evidenciadas foram atrofia de cardiomiócitos, vacuolização sarcoplasmática, ruptura de miofibras e fibras com padrão ondulado evidenciadas nas colorações de hematoxilina e eosina (HE), Tricrômico de Masson e Picrosírius. Na análise imuno-histoquímica utilizando o anticorpo anti-desmina houve uma imunomarcação reduzida ou inexistente em áreas com lesões histopatológicas. A imuno-histoquímica anti-desmina demonstrou ser uma importante ferramenta diagnóstica para caracterização de lesões de CMD em suínos. / Dilated cardiomyopathy (DCM) is a myocardial disease characterized by cardiac dilatation and reduced contractility of the left ventricular wall or both ventricles, the etiology of which is genetic or unknown. In pigs there are rare reports of DCM and are often related to ionosphere or gossypol poisoning. DCM outbreaks of unknown etiology in swine from herds in Brazil suggested the existence of a new, possibly nutritional, etiology. This study aimed to investigate the possible causes of DCM in pigs through macroscopic, microscopic, biochemical, chromatographical, molecular and immunohistochemical (IHC) evaluations, as well as the experimental reproduction of the disease. The project resulted in 2 scientific papers. The first article describes the clinical, pathological, chemical and toxicological findings of three DCM outbreaks in grower pigs, in addition to the experimental reproduction of this condition using the ration of one of the affected farms. For the experimental trial, 9 animals were divided into 3 groups; Group 1 received suspected ration only, Group 2 was fed a diet composed of half suspected ration plus half control ration, and group 3 received control ration only. Two pigs from group 1 presented clinical and pathological conditions similar to the natural cases after 8 days of consumption of the suspected ration. The main clinical signs observed were cough and severe dyspnea. At necropsy, bilateral cardiac dilatation, hydrothorax, hydropericardium, pulmonary edema, ascites and liver with the appearance of nutmeg were observed. The second article aimed to perform the histological, histochemical and immunohistochemical characterization of the cardiac lesions in 8 pigs with DCM and compare it with two control pigs. The main lesions evidenced were cardiomyocyte atrophy, sarcoplasmic vacuolization, rupture of myofibers and fibers with corrugated pattern evidenced in the staining of hematoxylin and eosin (HE), Masson's trichrome (MT) and Picrosírius (PS). Immunohistochemistry analysis using the anti-desmin antibody showed reduced or non-existent immunostaining in areas with histopathological lesions. The anti-desmin IHC proved to be an important tool for the diagnosis and characterization of DCM lesions in pigs.

Made available in DSpace on 2016-09-27T13:39:56Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-04-24. Added 1 bitstream(s) on 2016-09-27T13:45:04Z : No. of bitstreams: 1 000868433.pdf: 3954754 bytes, checksum: a069c800b7a52b72dcfe7658c6dbf75d (MD5) / A regurgitação aórtica (RA) determina sobrecarga de volume ao coração culminando com dilatação e hipertrofia excêntrica do ventrículo esquerdo. Uma das co-morbidades associada às doenças cardiovasculares é a depressão. Entre os antidepressivos mais prescritos encontramos os inibidores seletivos da recaptação da serotonina (ISRS). O tratamento com paroxetina (parox), um ISRS, preserva a fração de encurtamento do coração de ratos com RA. Alterações neurohumorais e periféricas podem estar envolvidas nessa melhora. A parox favorece a neurotransmissão serotoninérgica e pode aumentar a ocitocina e/ou peptídeos natriuréticos circulantes, ou pode ter ação direta sobre o coração melhorando a contratilidade cardíaca. Visando compreender melhor o efeito do tratamento com a parox na preservação da fração de encurtamento, verificamos a expressão de genes envolvidos com a hipertrofia e contratilidade cardíacas in vivo e in vitro. Para o estudo in vivo, ratos Wistar (280-300kg) foram submetidos à cirurgia de RA ou controle. A RA foi induzida por punção retrógrada dos folhetos valvares e as variáveis morfofuncionais foram analisadas por ecocardiograma, nas semanas 4 e 8 de observação. Os animais foram divididos em 4 grupos: RA+Parox, RA+Salina, Cont+Parox e Cont+Salina, e a partir da 4a semana parox (10mg/kg) foi administrada subcutaneamente por 4 semanas e salina foi utilizada como controle. Na 8a semana, os animais foram eutanasiados para a coleta do tecido cardíaco e posterior análise da expressão gênica por RT-qPCR de marcadores cardíacos de hipertrofia nos grupos experimentais. No estudo in vitro utilizamos a linhagem celular H9c2 para testar o efeito da parox (300μM) sobre essas células previamente desafiadas ou não com fenilefrina (fenil, 100μM). Os resultados in vivo mostraram que a RA produziu alterações morfofuncionais no coração relacionadas à sobrecarga de volume e aumentou a expressão gênica... / Aortic regurgitation (AR) causes volume overload to the heart culminating with left ventricle dilation and eccentric hypertrophy. A very common co-morbidity associated with cardiovascular disease is depression. Selective serotonin re-uptake inhibitors (SSRI) are widely prescribed as antidepressants. Our laboratory has showed that paroxetine (parox), an SSRI, treatment for 4 weeks prevented ventricular dilation preserving fractional shortening. Neurohumoral and peripheral changes might be involved in this improvement. Our hypothesis is that parox could act indirectly, in a oxytocin-dependent manner, or directly in the heart. Trying to understand the mechanism involved in the improvement of fractional shortening, we verify the expression of several genes involved in heart hypertrophy in vivo and in vitro. For the in vivo studies male Wistar rats (280-300kg) were submitted to AR surgery, by retrograde puncture of the aortic valves leaflets, or sham surgery. Morphofunctional variables of the hearts were analyzed by echocardiograms at week 4 and 8. The animals were divided in 4 groups: AR+Parox, AR+Saline, Sham+Parox and Sham+Saline. Parox (10mg/kg) was administered subcutaneously for 4 weeks and saline was used as control. At week 8 the animals were euthanized for tissue collection and posterior analysis of hypertrophic markers gene expression by RTq-PCR. To investigate the effects of parox in vitro we use H9c2 cell line. This cells were pre-treated or not with phenilephrine (phenil, 100μM), an α-adrenergic agonist, and then parox (300μM) was added to the culture. Our results show that AR model was able to produce morphofunctional changes, related to volume overload, in the heart and increase gene expression of cardiac hypertrophy markers. In addition, AR+Parox group preserved fractional shortening (45,67±1,52 vs 31,97±3,08) and decrease gene expression of β-MyHC (1,45±0,14 vs 1,97±0,15), microRNAs - 208b (1,29±0,09 vs 2,37±0,09) and...

Orientador: Robson Francisco Carvalho / Coorientador: Juliana Irani Fratucci De Gobbi / Banca: Lisete Compagno Michelini / Banca: Robson Francisco Carvalho / Banca: Valéria Cristina Sadrim / Resumo: A regurgitação aórtica (RA) determina sobrecarga de volume ao coração culminando com dilatação e hipertrofia excêntrica do ventrículo esquerdo. Uma das co-morbidades associada às doenças cardiovasculares é a depressão. Entre os antidepressivos mais prescritos encontramos os inibidores seletivos da recaptação da serotonina (ISRS). O tratamento com paroxetina (parox), um ISRS, preserva a fração de encurtamento do coração de ratos com RA. Alterações neurohumorais e periféricas podem estar envolvidas nessa melhora. A parox favorece a neurotransmissão serotoninérgica e pode aumentar a ocitocina e/ou peptídeos natriuréticos circulantes, ou pode ter ação direta sobre o coração melhorando a contratilidade cardíaca. Visando compreender melhor o efeito do tratamento com a parox na preservação da fração de encurtamento, verificamos a expressão de genes envolvidos com a hipertrofia e contratilidade cardíacas in vivo e in vitro. Para o estudo in vivo, ratos Wistar (280-300kg) foram submetidos à cirurgia de RA ou controle. A RA foi induzida por punção retrógrada dos folhetos valvares e as variáveis morfofuncionais foram analisadas por ecocardiograma, nas semanas 4 e 8 de observação. Os animais foram divididos em 4 grupos: RA+Parox, RA+Salina, Cont+Parox e Cont+Salina, e a partir da 4a semana parox (10mg/kg) foi administrada subcutaneamente por 4 semanas e salina foi utilizada como controle. Na 8a semana, os animais foram eutanasiados para a coleta do tecido cardíaco e posterior análise da expressão gênica por RT-qPCR de marcadores cardíacos de hipertrofia nos grupos experimentais. No estudo in vitro utilizamos a linhagem celular H9c2 para testar o efeito da parox (300μM) sobre essas células previamente desafiadas ou não com fenilefrina (fenil, 100μM). Os resultados in vivo mostraram que a RA produziu alterações morfofuncionais no coração relacionadas à sobrecarga de volume e aumentou a expressão gênica... / Abstract: Aortic regurgitation (AR) causes volume overload to the heart culminating with left ventricle dilation and eccentric hypertrophy. A very common co-morbidity associated with cardiovascular disease is depression. Selective serotonin re-uptake inhibitors (SSRI) are widely prescribed as antidepressants. Our laboratory has showed that paroxetine (parox), an SSRI, treatment for 4 weeks prevented ventricular dilation preserving fractional shortening. Neurohumoral and peripheral changes might be involved in this improvement. Our hypothesis is that parox could act indirectly, in a oxytocin-dependent manner, or directly in the heart. Trying to understand the mechanism involved in the improvement of fractional shortening, we verify the expression of several genes involved in heart hypertrophy in vivo and in vitro. For the in vivo studies male Wistar rats (280-300kg) were submitted to AR surgery, by retrograde puncture of the aortic valves leaflets, or sham surgery. Morphofunctional variables of the hearts were analyzed by echocardiograms at week 4 and 8. The animals were divided in 4 groups: AR+Parox, AR+Saline, Sham+Parox and Sham+Saline. Parox (10mg/kg) was administered subcutaneously for 4 weeks and saline was used as control. At week 8 the animals were euthanized for tissue collection and posterior analysis of hypertrophic markers gene expression by RTq-PCR. To investigate the effects of parox in vitro we use H9c2 cell line. This cells were pre-treated or not with phenilephrine (phenil, 100μM), an α-adrenergic agonist, and then parox (300μM) was added to the culture. Our results show that AR model was able to produce morphofunctional changes, related to volume overload, in the heart and increase gene expression of cardiac hypertrophy markers. In addition, AR+Parox group preserved fractional shortening (45,67±1,52 vs 31,97±3,08) and decrease gene expression of β-MyHC (1,45±0,14 vs 1,97±0,15), microRNAs - 208b (1,29±0,09 vs 2,37±0,09) and... / Mestre

Cardiomiopatia dilatada (CMD) é uma doença miocárdica caracterizada por dilatação cardíaca e redução da contratilidade da parede do ventrículo esquerdo ou de ambos os ventrículos, sendo a etiologia de origem genética ou desconhecida. Em suínos existem raros relatos de CMD, sendo frequentemente relacionados com intoxicações por ionóforos ou gossipol. Surtos de CMD de etiologia desconhecida em suínos de rebanhos comerciais no Brasil sugeriram a existência de nova etiologia, possivelmente nutricional. Este estudo teve como objetivo investigar as possíveis causas dos surtos de CMD em suínos, a partir de análises macroscópicas, microscópicas, bioquímicas, cromatográficas, moleculares, imuno-histoquímica (IHQ) e reprodução experimental. E teve como resultado 2 artigos científicos. O primeiro artigo descreve os achados clínicos, patológicos, químicos e toxicológicos de três surtos de CMD em suínos de crescimento, além da reprodução experimental desta condição utilizando a ração de uma das propriedades afetadas. Para o estudo experimental utilizou-se 9 animais divididos em 3 grupo; Grupo 1 recebendo ração suspeita, Grupo 2 metade ração suspeita mais metade de ração controle e o grupo 3 recebeu ração controle. Dois suínos do grupo 1 apresentaram condições clínicas e patológicas semelhantes aos casos naturais após 8 dias de consumo da ração suspeita. Os principais sinais clínicos observados eram tosse e dispneia grave. Na necropsia foram constatados dilatação cardíaca bilateral acentuada, hidrotórax, hidropericárdio, edema pulmonar, ascite e fígado com aspecto de noz moscada. O segundo artigo teve como objetivo fazer a caracterização histológica, histoquímica e imuno-histoquímica das lesões cardíacas em 8 suínos com CMD e compara-las com dois suínos controles. As principais lesões evidenciadas foram atrofia de cardiomiócitos, vacuolização sarcoplasmática, ruptura de miofibras e fibras com padrão ondulado evidenciadas nas colorações de hematoxilina e eosina (HE), Tricrômico de Masson e Picrosírius. Na análise imuno-histoquímica utilizando o anticorpo anti-desmina houve uma imunomarcação reduzida ou inexistente em áreas com lesões histopatológicas. A imuno-histoquímica anti-desmina demonstrou ser uma importante ferramenta diagnóstica para caracterização de lesões de CMD em suínos. / Dilated cardiomyopathy (DCM) is a myocardial disease characterized by cardiac dilatation and reduced contractility of the left ventricular wall or both ventricles, the etiology of which is genetic or unknown. In pigs there are rare reports of DCM and are often related to ionosphere or gossypol poisoning. DCM outbreaks of unknown etiology in swine from herds in Brazil suggested the existence of a new, possibly nutritional, etiology. This study aimed to investigate the possible causes of DCM in pigs through macroscopic, microscopic, biochemical, chromatographical, molecular and immunohistochemical (IHC) evaluations, as well as the experimental reproduction of the disease. The project resulted in 2 scientific papers. The first article describes the clinical, pathological, chemical and toxicological findings of three DCM outbreaks in grower pigs, in addition to the experimental reproduction of this condition using the ration of one of the affected farms. For the experimental trial, 9 animals were divided into 3 groups; Group 1 received suspected ration only, Group 2 was fed a diet composed of half suspected ration plus half control ration, and group 3 received control ration only. Two pigs from group 1 presented clinical and pathological conditions similar to the natural cases after 8 days of consumption of the suspected ration. The main clinical signs observed were cough and severe dyspnea. At necropsy, bilateral cardiac dilatation, hydrothorax, hydropericardium, pulmonary edema, ascites and liver with the appearance of nutmeg were observed. The second article aimed to perform the histological, histochemical and immunohistochemical characterization of the cardiac lesions in 8 pigs with DCM and compare it with two control pigs. The main lesions evidenced were cardiomyocyte atrophy, sarcoplasmic vacuolization, rupture of myofibers and fibers with corrugated pattern evidenced in the staining of hematoxylin and eosin (HE), Masson's trichrome (MT) and Picrosírius (PS). Immunohistochemistry analysis using the anti-desmin antibody showed reduced or non-existent immunostaining in areas with histopathological lesions. The anti-desmin IHC proved to be an important tool for the diagnosis and characterization of DCM lesions in pigs.

Introdução: A associação positiva entre circunferência da cintura (CC) e hipertensão arterial sistêmica (HAS), diabete melito (DM) e doença cardíaca (DC) é bem estabelecida e avaliada a partir de valores que evidenciaram essa associação em população adulta, porém, essa relação deve ser investigada em indivíduos idosos, devido às alterações fisiológicas desse grupo populacional. Objetivo: Analisar a associação entre valores de CC, mensurados em 2000, e HAS, DM E DC, referidas em 2006, e identificar valores de CC, com melhor capacidade discriminatória do risco para desenvolvimento dessas doenças, em idosos residentes no município de São Paulo. Métodos: Trata-se de estudo longitudinal com utilização de dados do Estudo SABE: Saúde, Bem-estar e Envelhecimento, realizado no município de São Paulo, em 2000 e em 2006. A população de estudo foi composta por idosos que não referiram HAS, DM e DC, em 2000, e que apresentavam valor de CC. As variáveis de estudo foram CC (variável contínua), índice de massa corporal (< 28 kg/m 2 e 28 kg/m 2 ), sexo, grupo etário (60 a 74 e 75) e etnia (caucasiana e outras), dados de 2000, e HAS, DM e DC referidas, em 2006. Para verificar a associação, utilizou-se o teste Rao & Scott (p<0,05) para amostra complexa, e regressão logística múltipla. A área sob a curva (AUC) ROC (Receiver Operating Caracteristics) foi utilizada para estimar o desempenho dos valores de CC, em discriminar corretamente idosos, segundo a referência ou não das doenças associadas à CC. Os valores críticos de CC foram identificados pelos maiores valores de razão de verossimilhança positiva, mantendo razão de verossimilhança negativa igual a zero. Para avaliar a capacidade discriminatória dos valores de CC identificados no presente estudo e dos valores de CC usualmente utilizados (CC 80 ou 88 cm, para mulheres, e CC 94 ou 102 cm, para homens), foi feita a comparação das AUC e respectivos intervalos de confiança de 95 por cento . Todos os cálculos foram realizados pelo programa estatístico Stata versão 10.0. Resultados: Foram analisados 405 idosos, dos quais 26,9 por cento referiram HAS, 4,1 por cento DM e 10,0 por cento DC. A CC, em 2000, manteve-se como fator de risco para referência de DM, em 2006, independente do sexo, grupo etário, etnia e índice de massa corporal (OR 1,10; IC 95 por cento 1,05-1,16; p=0,000; p do modelo=0,000). A AUC mostrou desempenho satisfatório dos valores críticos de CC, na discriminação da referência de DM, para mulheres e homens, de 60-74 anos. Os valores críticos de CC, identificados foram 87 cm para mulheres e 99 cm para homens, os quais apresentaram melhor desempenho segundo o valor de AUC, em comparação aos valores usualmente utilizados. Conclusão: Os valores críticos de CC, identificados no presente estudo, para indivíduos de 60-74 anos, apresentaram melhor capacidade discriminatória da referência de DM, em 6 anos, quando comparado aos valores de CC usualmente utilizados / Background: The positive association between waist circumference (WC) and hypertension (H), diabetes mellitus (DM) and heart disease (HD) is well established and evaluated from critic values that showed this association in adults, however, this relationship must be investigated in the elderly due to physiological changes in this population group. Objective: To analyze the association between WC values, measured in 2000, and H, DM and HD, reported in 2006, and identify WC values, with better discriminatory capacity of the risk for developing these diseases, in elderly residents in the municipality of São Paulo. Methods: This was a longitudinal study using data from the SABE Survey: Health, Wellness and Aging, held in São Paulo, in 2000 and 2006. The study population was comprised of elderly individuals who did not report H, DM and HD in 2000, and who had WC value. The study variables were WC (continuous variable), body mass index (<28 kg/m and 28 kg/m 2 ), sex, age group (60 to 74 and 75), and ethnicity (caucasian and others), information of 2000, and H, DM and HD, reported in 2006. To verify the association, the Rao & Scott test for complex sample was used (p <0.05), and multiple logistic regression. The area under the ROC (Receiver Operating Caracteristics) curve (AUC) was used to estimate the performance of WC values in correctly discriminating elderly, according to the reference or not of diseases associated with WC. WC critical values were identified by the highest positive likelihood ratio, and negative likelihood ratio equal to zero. To assess the discriminatory capacity of WC values identified in this study and the WC values commonly used (WC 80 ou 88 cm, for women, e WC 94 ou 102 cm, for men) was made the comparison of AUC and confidence intervals of 95 per cent . All calculations carried out by using Stata version 10.0. Results: Four hundred five elderly people were analyzed, of which 26.9 per cent reported H, 4.1 per cent DM and 10.0 per cent HD. The WC value in 2000, was a risk factor for DM reference, in 2006, regardless of sex, age group, ethnicity and body mass index (OR 1.10, 95 per cent CI 1.05-1.16, p=0.000, p model=0.000). The AUC showed satisfactory performance of WC critical values, in discriminating the DM reference to women and men of 60-74 years. The WC critical values identified were 87 cm, for women, and 99 cm, for men, which showed better performance according to the AUC value compared to the WC values commonly used. Conclusion: The WC critical values identified in this study, for individuals of 60-74 years, showed better discriminatory ability of reference of DM, in period of 6 years, compared to the WC values commonly used

Social inequalities in health have been well documented in the literature. Despite the universal health care system and detailed measures of health surveillance, socioeconomic disparities related to cardiovascular diseases (CVD) remain present and are predicted to increase due to growing socioeconomic inequalities (Pampalon, 2008). Many health policy initiatives, such as the development of cardiac rehabilitation programs, were put in place in order to promote heart healthy lifestyles. These programs are provided as a medical and educational solution to prevent, manage, and lower risks of developing complications due to cardiovascular diseases, yet participation rates are as low as 37% for eligible individuals (Heart and Stroke Foundation of Canada, 2013). By drawing chiefly on Pierre Bourdieu’s sociocultural theory of practices, this qualitative study aims to understand the social variation of lifestyles in the context of cardiac rehabilitation of two groups of men from contrasting socioeconomic conditions. Sixty in-depth interviews were conducted with francophone men (mean age of 56.5) from the Outaouais region (Québec, Canada) who have suffered from a cardiac event requiring hospitalization. A number of studies on cardiovascular health have indicated health and lifestyle disparities among the male population. In order to provide a new perspective, this specific study drew principally on the notion of social capital in order to provide a more complete understanding of the social variation of lifestyles in the context of cardiac rehabilitation, particularly the impact these socioeconomic differences have on the quality of participants’ social capital, and how it shapes lifestyles after a heart intervention The results of this study are presented in an article which compares lifestyles and cardiac rehabilitation practices on the basis of three concepts of social capital, – social cohesion, trust, and social support. Results suggests that socioeconomic conditions influence levels of social cohesion, trust, and the quality of social support provided by social networks in the context of cardiac rehabilitation. Despite the underprivileged participant’s awareness of normative health lifestyles, they also were constrained by socio-cultural barriers, which limited a heart-healthy lifestyle.

Cognitive ratings that use bipolar constructs based upon similarity and contrast have been shown to be biased towards the similarity pole in approximately a 62/38 ratio. This bias has also been known to shift in the contrastive direction for individuals who have psychiatric problems. This quantitative measure of cognitive change has a potential for characterizing cognitive changes that occur during the disease process, including recovery from disease. The present study investigated changes in self-aspect ratings and bipolar construct use in adult male veterans who had undergone coronary artery bypass graft surgery. Results indicated that treatment subjects' self-aspect and construct ratings were more negative than controls'. Results also indicated that all subjects rated core interpersonal self-aspects closest to the expected bias, while self-aspects related to cardiac recovery problems were rated in the most contrastive direction. The results finally suggested that the greatest degree of change for the treatment subjects were in emotionally generated constructs. The results suggested a preliminary validation for characterizing cognitive changes in the disease process by measuring shifts in bipolar construct ratings.

An essential task for a pacemaker or implantable defibrillator is the accurate identification of rhythm categories so that the correct electrotherapy can be administered. Because some rhythms cause a rapid dangerous drop in cardiac output, it is necessary to categorize depolarization waveforms on a beat-to-beat basis to accomplish rhythm classification as rapidly as possible. In this thesis, a depolarization waveform classifier based on the Lifting Line Wavelet Transform is described. It overcomes problems in existing rate-based event classifiers; namely, (1) they are insensitive to the conduction path of the heart rhythm and (2) they are not robust to pseudo-events. The performance of the Lifting Line Wavelet Transform based classifier is illustrated with representative examples. Although rate based methods of event categorization have served well in implanted devices, these methods suffer in sensitivity and specificity when atrial, and ventricular rates are similar. Human experts differentiate rhythms by morphological features of strip chart electrocardiograms. The wavelet transform is a simple approximation of this human expert analysis function because it correlates distinct morphological features at multiple scales. The accuracy of implanted rhythm determination can then be improved by using human-appreciable time domain features enhanced by time scale decomposition of depolarization waveforms. The purpose of the present work was to determine the feasibility of implementing such a system on a limited-resolution platform. 78 patient recordings were split into equal segments of reference, confirmation, and evaluation sets. Each recording had a sampling rate of 512Hz, and a significant change in rhythm in the recording. The wavelet feature generator implemented in Matlab performs anti-alias pre-filtering, quantization, and threshold-based event detection, to produce indications of events to submit to wavelet transformation. The receiver operating characteristic curve was used to rank the discriminating power of the feature accomplishing dimension reduction. Accuracy was used to confirm the feature choice. Evaluation accuracy was greater than or equal to 95% over the IEGM recordings.

The objective of the current study is to present the case of an intercollegiate basketball player diagnosed with an ifliopathic cardiomyopathy. The athlete illustrated in the case study experienced ongoing chest discomfort with exercise. Episodic chest pain and syncope in athletes is often alarming and may signal an underlying cardiac condition. Early recognition and maJagement of these athletes is vital to the prevention of sudden cardiac death (SCD). Fortunately, the athlete was referred to a cardiologist by her team physician during her pre-participation physical examination to rule out heart conditions that may lead to SCD. The athlete was presented a mildly reduced ejection fraction during her screening with the cardiologist. In cardiovascular physiology, ejection fraction is the fraction of end-diastolic volume that is ejected from the ventricle with each heart beat. Damage to the myocardium, as seen in cardiomyopathies, decreases the heart's ability to eject blood and therefore reduces the ejection fraction. The athlete underwent VO2max testing as well where it was discovered that her VO2max was exceptionally low for a physically active division-I athlete. This low VO2max suggested that the athlete had an insufficient oxygen uptake during intense exercise. The athlete experienced a treatment protocol consisting of a progressive conditioning regimen of additional cardiovascular exercise that proved to be effective in raising her VO2max by 10%. The athlete returned to full participation and remained asymptomatic throughout the remainder of the season. The pre-participation physical examination is crucial in early detection of events that may lead to sudden cardiac death. A thorough history and physical examination are the most efficient screening methods for detecting cardiovascular abnormalities. Any athlete with episodes of syncope, hypertension, or changes in heart rhythm should be referred to a physician.

Indiana University-Purdue University Indianapolis (IUPUI) / Coronary microvascular function is markedly impaired by the onset of the metabolic syndrome and may be an important contributor to the increased cardiovascular events associated with this mutlifactorial disorder. Despite increasing appreciation for the role of coronary K+ channels in regulation of coronary microvascular function, the contribution of K+ channels to the deleterious influence of metabolic syndrome has not been determined. Accordingly, the overall goal of this investigation was to delineate the mechanistic contribution of K+ channels to coronary microvascular dysfunction in metabolic syndrome. Experiments were performed on Ossabaw miniature swine fed a normal maintenance diet or an excess calorie atherogenic diet that induces the classical clinical features of metabolic syndrome including obesity, insulin resistance, impaired glucose tolerance, dyslipidemia, hyperleptinemia, and atherosclerosis. Experiments involved in vivo studies of coronary blood flow in open-chest anesthetized swine as well as conscious, chronically instrumented swine and in vitro studies in isolated coronary arteries, arterioles, and vascular smooth muscle cells. We found that coronary microvascular dysfunction in the metabolic syndrome significantly impairs coronary vasodilation in response to metabolic as well as ischemic stimuli. This impairment was directly related to decreased membrane trafficking and functional expression of BKCa channels in vascular smooth muscle cells that was accompanied by augmented L-type Ca2+ channel activity and increased intracellular Ca2+ concentration. In addition, we discovered that impairment of coronary vasodilation in the metabolic syndrome is mediated by reductions in the functional contribution of voltage-dependent K+ channels to the dilator response. Taken together, findings from this investigation demonstrate that the metabolic syndrome markedly attenuates coronary microvascular function via the diminished contribution of K+ channels to the overall control of coronary blood flow. Our data implicate impaired functional expression of coronary K+ channels as a critical mechanism underlying the increased incidence of cardiac arrhythmias, infarction and sudden cardiac death in obese patients with the metabolic syndrome.