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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
481

Marcadores cardíacos em ratos (Rattus norvegicus) infectados experimentalmente por Toxocara canis / Cardiacs markers in rats (Rattus norvegicus) experimentally infected by Toxocara canis

Freitas, Selma Bastos Zambelli 21 June 2010 (has links)
Made available in DSpace on 2016-07-18T17:53:07Z (GMT). No. of bitstreams: 1 Dissertacao.pdf: 208468 bytes, checksum: 9493c81d791b19a0b7ecb64fc69e95f8 (MD5) Previous issue date: 2010-06-21 / With the aim of studying the changes promoted by larvae of Toxocara canis on the cardiac enzymes creatine kinase (CK), creatine kinase MB fraction (CK-MB) and lactate dehydrogenase (LDH) from rats three months old, according to load infective and time, two groups were formed with 24 animals, 12 males and 12 females per group. The animals received 250 (Group I) and 1000 (Group II) eggs larvae of T. canis, orally. Another group, consisting of 12 animals, six of each sex served as controls. On day seven, 15, 30, 60, 120 and 180 post-infection was performed in each moment, the euthanasia of four animals from each of the two experimental groups and control group. Blood samples were collected by puncturing the caudal vena cava. The peaks of enzyme activity measured in animals infected with 250 eggs preceded those of animals that received 1000 eggs. It can be concluded that the lower the infective load faster is to increase the activity of enzymes used as markers and cardiac changes are more precocious in other tissues as compared to the heart muscle. / Com o objetivo de estudar as alterações promovidas por larvas de Toxocara canis sobre as enzimas cardíacas creatinoquinase (CK), creatinoquinase fração MB (CK-MB) e lactato desidrogenase (LDH) de ratos Wistar de três meses de idade, em função da carga infectante e do tempo, foram formados dois grupos com 24 animais, 12 machos e 12 fêmeas por grupo. Os animais receberam 250 (Grupo I) e 1000 (Grupo II) ovos larvados de T. canis, por via oral. Outro grupo, constituído por 12 animais, seis de cada sexo, serviu como controle. Nos dias sete, 15, 30, 60, 120 e 180 pós-infecção, foi realizada, em cada momento, a eutanásia de quatro animais de cada um dos grupos experimentais e dois do grupo controle. Amostras de sangue foram colhidas por punção da veia cava caudal. Os picos de atividade das enzimas avaliadas nos animais infectados com 250 ovos antecederam aqueles dos animais que receberam 1000 ovos. Pode-se concluir que quanto menor a carga infectante mais rápida é a elevação de atividade das enzimas utilizadas como marcadores cardíacos e as alterações são mais precoces em outros tecidos, quando comparadas à musculatura cardíaca.
482

Planejamento e organização de um centro de reabilitação para o paciente cardíaco: análise da situação atual / Planning and organization of a rehabilitation center for the cardiac patient: analysis of the current situation

Andrade, Januario de 12 April 1978 (has links)
Tratou-se de início o problema da reabilitação do cardíaco a partir de uma fundamentação de seus conceitos e análise de sua história. Em seguida estudou-se os aspectos orgânico, social e psíquico que influem no atendimento do paciente coronariano. A partir destes elementos elaborou-se uma metodologia para a reabilitação deste tipo de paciente. Ressaltou-se a importância da equipe de atendimento, bem como recursos de equipamento e planta física. Caracterizou-se a equipe como multiprofissional e multidisciplinar e definiu-se suas atribuições. Estudou-se a situação atual da reabilitação cardíaca no Brasil, com a finalidade de possibilitar o planejamento e a organização de um serviço de reabilitação para o paciente cardíaco, devido ao aumento da morbimortalidade por doença coronariana. Procurou-se determinar a localização geográfica, a situação e os tipos de serviços de reabilitação cardíaca no Brasil, usando-se questionários enviados pelo correio aos serviços de cardiologia do país, indexados no Anuário Estatístico. Realizou-se a análise in loco dos serviços de reabilitação cardíaca da capital do Estado de São Paulo. Posteriormente, comparou-se os demais serviços com o Instituto \"Dante Pazzanese\" de Cardiologia (IDPC). Para se obter dados mais precisos analisou-se a planta física, os recursos humanos, o equipamento, a administração e a avaliação dos serviços de reabilitação cardíaca. Verificou-se que os serviços de reabilitação cardíaca estão localizados apenas nas Regiões Sul (5) e Sudeste (15), incluindo o IDPC. Foi verificado que nas Regiões Sul e Sudeste encontram-se 64.571.000 habitantes o que eventualmente poderá gerar 6.457 cardiopatas. Nestas mesmas áreas notou-se que existe um cardiologista para atender 1.793.638 habitantes. Constatou-se, por outro lado, que as necessidades em área para condicionamento físico, salas para atendimento, pessoal e equipamento necessário são bastante deficientes nas duas Regiões, principalmente quando comparadas à organização do IDPC, que foi utilizada como padrão. Concluiu-se pela necessidade de se encarar a reabilitação cardíaca como um processo dinâmico, que depende do trabalho da equipe, do equipamento, da planta física, da orientação e educação do paciente e seus familiares, da motivação da comunidade, e que o serviço de reabilitação cardíaca não pode estar desvinculado do Hospital e da Comunidade para a qual foi criado. É necessária a preparação de equipes multidisciplinares para suprir as Regiões carentes em reabilitação do paciente cardíaco, bem como a criação de unidades que atendam às necessidades. / The problem of the cardiac patient rehabilitation was initially studied, taken into consideration its concepts and its clinical history. Next, organic, social and psychological aspects that influence the attendance of coronary patients were studied. Based on these elements, rehabilitation methodology for these patients was elaborated. The importance of the attending team, as well as of equipment and physical plant, was stressed. The team was characterized as a multiprofessional and multidisciplinary one and the role of each member was defined. The current situation of cardiac rehabilitation in Brazil was studied, in order to facilitate the planning and organization of a rehabilitation service for cardiac patients, since morbidity and mortality caused by coronary disease are increasing. An attempt was done in order to point out the geographic area, the actual situation and the types of the cardiac rehabilitation services in Brasil. This was done by means of a questionnaire mailed to the indexed services in the \"ANUÁRIO ESTATÍSTICO DO BRASIL\". Concomitantly, an analysis \"in loco\" of the cardiac rehabilitation services in São Paulo City was performed and latter on all services were compared to Instituto \"Dante Pazzanese\" de Cardiologia. In order to obtain more precise data, the plant, human resources, equipment, administration and evaluation of services were analysed. It was found that the cardiac rehabilitation services are located in the southerhand south-eastern areas of Brazil only, where we can find 64.571,000 inhabitants which can eventually present 6.457 cases of cardiopathy. These areas present 1 (one) cardiologist to attend to 1,793,638 inhabitants. On the other hand, the existing material and equipment, as well as appropriate buildings are deficient in both areas, mainly when compared to IDPC organization, that was used as model. It was concluded that we must consider cardiac rehabilitation as a dynamic process, dependant on the work of a team, on the equipment, on the building, on the orientation and education of the patient and his family, on the motivation of the community, and that the cardiac rehabi1itation service cannot be separated Cdetached) from the Hospital and the community it was created for.
483

Cardiac gene therapy with phosphodiesterase PDE4B in a mouse model of heart failure / Surexpression cardiac de PDE4B1 à l'aide d'un virus adéno-associé

Margaria, Jean Piero 26 January 2018 (has links)
L'activation de la voie β-adrénergique entraîne une augmentation de l'AMPc qui joue un rôle clé dans la régulation de la contraction cardiaque. Alors qu'une stimulation aiguë des récepteurs β-adrénergiques (β-AR) améliore la fonction cardiaque, leur activation chronique dans l'insuffisance cardiaque (IC) est préjudiciable au cœur, car elle favorise la dérégulation du calcium intracellulaire et le remodelage pathologique du cœur. Les phosphodiestérases (PDE) sont responsables de la dégradation de l'AMPc et de la compartimentation, et donc ajustent finement les réponses β-AR. Nous avons montré précédemment que la PDE4B est diminuée dans l'hypertrophie cardiaque pathologique et que l'ablation de PDE4B chez la souris exacerbe la stimulation β-AR du courant Ca2+ de type L et la propension aux arythmies cardiaques. Étant donné qu'un traitement à long terme par des inhibiteurs de la PDE augmente la mortalité dans l'HF, nous avons supposé que la diminution des taux d'AMPc pourrait avoir un effet thérapeutique dans cette maladie. Nous avons exploré si la surexpression cardiaque médiée par les vecteurs viraux adéno-associés sérotype 9 (AAV9) ou à l’aide d’un système transgénique de PDE4B pourrait prévenir une hypertrophie dans un modèle murin d'infusion chronique d'isoprotérénol (Iso) (60 μg / g / jour pendant 2 semaines). L'échocardiographie a permis l'exploration de la fonction cardiaque. L'expression de la protéine PDE4B dans les extraits de coeur a été mesurée par western blot. Des coupes de cœur (10 μm d'épaisseur) ont été prélevées sur des échantillons inclus en paraffine et colorées avec le trichrome de Masson pour quantifier la fibrose. Une augmentation de dix fois et cinq fois des niveaux de protéines PDE4B a été mesurée dans les transgéniques et les AAV9, respectivement. Chez les souris transgéniques adulte, la surexpression constitutive de la PDE4B a provoqué une légère hypertrophie. Chez les souris témoins, de type sauvage ou ayant reçu un AAV9 codant pour la Luciferase(1x1012 particules virales), le traitement par Iso chronique a induit une hypertrophie cardiaque, une fibrose et une diminution de la fraction d'éjection (EF) mesurée par échocardiographie. La surexpression de PDE4B n'a pas empêché l'hypertrophie cardiaque induite par Iso, mais a aboli l'augmentation de la fibrose. Plus important encore, l’EF a été préservé lorsque PDE4B a été surexprimé dans ce modèle pathologique. Au total, ces résultats suggèrent que la thérapie génique avec des AAV9 codant pour PDE est une approche thérapeutique potentielle pour le traitement de l'hypertrophie cardiaque inadaptée. / Activation of the β-adrenergic pathway results in an increase in cAMP which plays a key role in the regulation of cardiac contraction. While an acute stimulation of the β-adrenergic receptors (β-ARs) improves cardiac function, their chronic activation in heart failure (HF) is detrimental to the heart, as it promotes deregulation of intracellular calcium handling and maladaptive remodeling. Multiple phosphodiesterases (PDEs) are responsible for cAMP degradation and compartmentation, and therefore finely tune β-AR responses. We showed previously that PDE4B is decreased in pathological cardiac hypertrophy and PDE4B ablation in mice exacerbates β-AR stimulation of the L-type Ca2+ current and the propensity to cardiac arrhythmias. Since long term treatment with PDE inhibitors increases mortality in HF, we hypothesized that decreasing cAMP levels could have a therapeutic effect in this disease. To address this hypothesis we used two different models: transgenic overexpression of the PDE using the cardiac specific promoter α-MHC, and PDE-encoding adeno-associated virus targeting the heart in adult mice. We explored whether transgenic or serotype 9 adeno-associated viral vectors (AAV9) mediated cardiac overexpression of PDE4B could prevent maladaptive hypertrophy in a mouse model of chronic isoproterenol (Iso) infusion (60 µg/g/day during 2 weeks). Echocardiography allowed cardiac function exploration. PDE4B protein expression in heart extracts was measured by western blot. Heart sections (10 µm thick) were cut from paraffin-embedded specimens and stained with Masson’s trichrome to quantify fibrosis. A ten-fold and five-fold increase in PDE4B protein levels was measured in transgenic and AAV9, respectively. In transgenic mice, constitutive PDE4B overexpression caused a mild hypertrophy in adult mice. In control mice, either wild-type or injected with a AAV9 encoding for (1x1012 vp), chronic Iso treatment induced cardiac hypertrophy, fibrosis, and decreased ejection fraction (EF) measured by echocardiography. Overexpression of PDE4B did not prevent cardiac hypertrophy induced by Iso, but abolished the increase in fibrosis. More importantly, EF was preserved when PDE4B was overexpressed in this pathological model. Altogether, these results suggest that gene therapy with AAV9 encoding PDEs is a potential therapeutic approach for cardiac maladaptive hypertrophy.
484

The knowledge of impending heart attack and by-stander cardiopulmonary resuscitation among students at Turfloop Campus University of Limpopo South Africa

Nkoko, Koena Joseph January 2007 (has links)
Thesis (MPH) -- University of Limpopo, 2007. / Aim of the study: To determine knowledge of CPR and heart attack or cardiac arrest signs and symptoms among university students. Study Design: A questionnaire based descriptive, cross – sectional study. Setting: University of Limpopo – Turfloop Campus in Limpopo Province of South Africa. Subjects: A total sample of 400 students participated in the study. The sample was selected randomly using simple random sampling techniques. Outcome measures: The faculty, age, gender and level of study were determined as well as the knowledge each student has on signs and symptoms of impending heart attack and CPR. Results: Of the 400 students only 26% (n=104) knew the signs and symptoms of an impending heart attack as well as out of hospital management of heart attack by performing CPR. There were differences between and within faculties, age groups, gender and level of study. Based on the Bonferroni test the student from faculty of Sciences, Health and Agriculture are more likely (p-value 0017) to know when to perform CPR compared to students from other faculties. Level of study is not associated (p-value 0128) with how much the students know about the timing and indications of CPR. Overall female students performed worse with 79% (n=123) responding incorrectly to the questions compared to 69% (n=169) males. Conclusion: Based on the results of this study it safely can be concluded that the students’ knowledge of signs and symptoms of an impending heart attack and CPR procedure is poor. It is therefore important for the university as a center of teaching and learning to consider including as part of university curriculum, basic life support v and first aid courses which include CPR. The inclusion of basic life support and first aid in university curriculum will prepare students to be able to effectively manage out of hospital heart attack and reduce mortality resulting from the latter. The findings of this study might to a certain extent be reflecting what the public’s knowledge on the subject is, hence the need for the policy makers to take serious note of the findings when public health promotion programmes are developed.
485

Changes in cardiac troponin I concentration and echocardiographic parameters after semen collection in stallions

Viljoen, Adrienne 03 January 2011 (has links)
This dissertation focuses on the effect of breeding on the myocardium of stallions using cardiac troponin I (cTnI) as the preferred blood biomarker for detection of myocardial cell injury. Haematological, echocardiographic and heart rate (HR) parameters are also reported. Fourteen clinically healthy phantom-trained stallions were assessed. Cardiac troponin I concentration was determined pre-semen collection and at 4, 6, 12 and 24 hours following semen collection. Predictors that were measured included mean HR during each stage of semen collection, maximum HR, area under the curve for HR and fractional shortening (FS). Pre-semen collection cTnI concentrations were within reported reference ranges for all stallions. Following semen collection, cTnI concentration was significantly increased at 4 and 6 hours post-semen collection. Results also suggest that the HR of stallions peak during mounting of the phantom. Five stallions failed to show an expected increase in FS immediately post-semen collection. No association was identified between the measured predictors and increased cTnI concentration. This study concluded that cTnI concentration may increase in stallions following semen collection although the clinical significance of this observed increase in healthy stallions is unclear without histopathological evaluation of the myocardium. No conclusion regarding FS immediately post-semen collection could be drawn from results in this study. The research reported in this dissertation can serve as a reference for future studies investigating cTnI concentrations in stallions. / Dissertation (MSc)--University of Pretoria, 2010. / Companion Animal Clinical Studies / unrestricted
486

A comparison of sufentanil versus remifentanil in fast-track cardiac surgery patients

Zakhary, Waseem Zakaria Aziz 08 January 2020 (has links)
The main drives of development of fast track cardiac anaesthesia are the increase burden of health care cost and the shortage of intensive care beds. Fast track (FT) is multidisciplinary process that leads to rapid patient recovery and discharge without affecting morbidity and mortality. Fast track cardiac anaesthesia (FTCA) was proved to be safe, efficient and economically effective. Leipzig FT protocol was first introduced in November 2005 for elective cardiac surgery patients in the heart center of Leipzig University. It is characterized by using intraoperative remifentanil as main opioid with treating the patients postoperatively in post-anaesthesia care unit (PACU) completely bypassing ICU admission. Remifentanil was unavailable in Germany from February to July 2017, therefore the protocol had to be modified and sufentanil was used instead. The aim of this retrospective study was to compare the effects of remifentanil and sufentanil on the well-established FT concept. The primary end points were ventilation time, LOS in PACU (LOS PACU), the visual analogue score (VAS) and the piritramide consumption on the day of operation. The secondary end points were LOS in intermediate care (LOS IMC), hospital LOS, FT failure (FTF), in-hospital mortality and postoperative complications such as postoperative nausea and vomiting (PONV), delirium and the incidence of reintubation. All cardiac surgery patients consecutively admitted to PACU during the period from February to July 2017 (n=622), received sufentanil (FT-S), were compared to patients (n=679) from the same time period of the previous year treated with continuous remifentanil infusion (FT-R) according to the standard FT protocol. To minimise selection bias and to obtain comparable groups, we used a 1:1 nearest neighbour propensity score matching approach resulted in total 1218 patients divided in 2 equal groups. In FT-R, an uninterrupted continuous infusion of remifentanil (0.2-0.3 µg/kg/min) was used for maintenance of anaesthesia throughout the whole operation. In FT-S, a continuous infusion of sufentanil was used during maintenance of anaesthesia as follows: 1 µg/kg/h until sternotomy, 0.5 µg/kg/h until cardiopulmonary bypass and 0.25 µg/kg/h until chest closure, then the infusion was stopped. Otherwise, the Leipzig FT protocol was used as previously published. Remifentanil was more effective in reducing time to extubation (by 40 minutes) and length of stay in the post anaesthetic care unit during fast track cardiac anaesthesia than sufentanil. There was an increased need of piritramide when remifentanil was used. The hospital length of stay was longer in remifentanil group. There were no differences between both groups regarding postoperative complications. Clinically, a detailed and time-directed weaning protocol is more important than the use of a specific opioid during fast track treatment in cardiac surgery patients.:TABLE OF CONTENTS 1. List of Abbreviations 3 2. Bibliographic description 5 3. Abstract 5 4. Introduction 6 4.1 Fast-track cardiac anaesthesia 6 4.1.1 Definitions 6 4.1.2 Current evidence of FTCA 7 4.1.2.1 The safety of FTCA 7 4.1.2.2 The efficiency of FTCA 7 4.1.2.3 Economic Implications of FTCA 8 4.1.3 Different FTCA pathways 8 4.1.4 Patient selection and optimization 9 4.1.5 Anaesthesia aspects of FT 11 4.1.6 Cardiopulmonary bypass aspects of FT 12 4.2 Leipzig FT Protocol 12 4.3 Opioids 16 4.3.1 Remifentanil 16 4.3.2 Sufentanil 17 5. Objective of the work 19 6. Materials and Methods 19 7. Results 21 8. Discussion 26 9. Publication manuscript: „ A comparison of sufentanil versus remifentanil in fast-track cardiac surgery patients “Anaesthesia 2019, 74, 602–608“. 30 10. Summary 37 11. Bibliography 39 12. Appendix (Anlagen): 43 12.1 Declaration of Independence (Selbstständigkeitserklärung) 43 12.2 Declaration of co-authors’ contribution 44 12.3 Publications 45 12.4 Acknowledgment 46
487

The Rarest of the Rare: A Case of Primary Cardiac Osteosarcoma

Manthri, Sukesh, Youssef, Bahaaeldin, Chakraborty, Kanishka, Jaishankar, Devapiran 21 April 2020 (has links)
Most cardiac tumors are metastatic tumors, which are 20–40 times more common than primary tumors of the heart. Most primary tumors of the heart are benign, with atrial myxomas being the most common. Primary cardiac tumors are extremely rare with an incidence of less than 0.1 percent. Virtually all types of sarcomas have been reported in the heart as isolated case reports. We present a rare case of biatrial high-grade osteosarcoma. A fifty-four-year-old Hispanic female presented with shortness of breath and was cyanotic on the exam while visiting Mexico. Due to abnormal chest x-ray, echocardiogram concerning for bilateral atrial myoma she was referred to a cardiothoracic surgeon. She underwent bi atrial intracardiac tumor resection in Mexico. Several months prior to her resection she noted numbness on the side of the face that was evaluated by her physicians in the United States with a Brain MRI and carotid Ultrasound/Doppler that was unrevealing. She also remembered an episode of uncontrolled hypertension two years prior to surgery requiring admission to a local hospital in East Tennessee with cardiology evaluation that did not include an echocardiogram. Surgical pathology showed extensive undifferentiated spindle cell proliferation with multifocal osteoid production and foci of osseocartilaginous differentiation. There was prominent necrosis and moderately high mitotic rate (10-19/HPF). Tumor cells were positive for SatB2 and negative for vascular, muscular, or neural markers. This is consistent with a primary cardiac high-grade osteosarcoma. These occur very rarely, usually in the atria, and behave aggressively. Post resection staging PET-CT showed hypermetabolic mixed lytic and sclerotic lesion of T10 concerning for metastasis disease. She received approximately 6 cycles of adriamycin and ifosfamide chemotherapy. Adriamycin was discontinued due to left ventricular dysfunction with an ejection fraction of 30-35%, multiple segmental abnormalities, diffuse left ventricular hypokinesis, and moderate to severe mitral valve regurgitation. Despite intracardiac tumor, resection, concern for metastatic disease, chemotherapy, and systolic dysfunction patient is asymptomatic and does have robust performance status. A follow-up PET-CT five months after cessation of treatment reveals no significant evidence of uptake other than abnormalities in the T10 vertebra. A repeat echocardiogram continues to reveal a depressed ejection fraction of 35%. The patient is completely asymptomatic, seemingly fit with an ECOG performance status of 0-1. Osteosarcomas are aggressive with a high incidence of recurrence and metastasis. Fewer than 50 cases of primary cardiac osteosarcomas have been reported in the literature. Currently, it is postulated that they arise from undifferentiated mesenchymal stem cells in the endocardium that transform into active osteoblasts. Even though complete resection can be achieved in some cases, long-term results are usually poor. No standard therapy has been established due to the tumor's low incidence rate and lack of clinical trial data. Our case highlights the importance of evaluating common symptoms thoroughly since it may be a harbinger of rare and serious disorders. This case reflects the heterogeneous nature of sarcoma histology, the consequent tumor biology and hence varied clinical course and prognosis.
488

Micropatterned Fibrin Hydrogels for Increased Cardiomyocyte Alignment

English, Elizabeth J 13 November 2019 (has links)
Cardiovascular disease is the leading cause of death in the US, which can result in blockage of a coronary artery, triggering a myocardial infarction (MI). After a MI, hypoxic ventricular myocardial tissue dies, resulting in the deposition of non-contractile scar tissue and remodeling of the ventricle, leading to decreased cardiac output and ultimately heart failure. Currently, the gold-standard solution for total heart failure is a heart transplant. As donor hearts are in short supply, an alternative to total-organ transplantation is surgically remodeling the ventricle with the implantation of a cardiac patch. Acellular cardiac patches have previously been investigated using synthetic or decellularized native materials in effort to improve cardiac function. However, a limitation of this strategy is that acellular cardiac patches only reshape the ventricle and do not increase cardiac contractile function. By incorporating the use of a clinically relevant cell type and by matching native architecture, we propose the use of a highly aligned fibrin scaffold to support the maturation of human induced pluripotent stem cell cardiomyocytes (hiPS-CM) for use as a cell-populated cardiac patch. By micropatterning fibrin hydrogels, hiPS-CM seeded on the surface of this scaffold become highly aligned, which is crucial for increased contractile output. Our lab previously developed a composite fibrin hydrogel and microthread cardiac patch matching mechanical properties of native myocardium. By micropatterning fibrin hydrogel alone, we were able to match cellular alignment of hiPS-CM to that of native myocardium. hiPS-CMs seeded on this surface were found to express distinct sarcomere alignment and circumferential connexin-43 staining at 14 days of culture as well as cellular elongation, which are necessary for mature contractile properties. Constructs were also cultured under electrical stimulation to promote increased contractile properties. After 7 days of stimulation, contractile strains of micropatterned constructs were significantly higher than unpatterned controls. These results suggest that the use of topographical cues on fibrin scaffolds may be a promising strategy for creating engineered myocardial tissue to repair damaged myocardium.
489

The Role of Human Antigen R (HuR) in Pathological Cardiac Remodeling

Green, Lisa 24 May 2022 (has links)
No description available.
490

HSPA12B Attenuates Cardiac Dysfunction and Remodelling After Myocardial Infarction Through an Enos-Dependent Mechanism

Li, Jingjin, Zhang, Yangyang, Li, Chuanfu, Xie, Jian, Liu, Ying, Zhu, Weina, Zhang, Xiaojin, Jiang, Surong, Liu, Li, Ding, Zhengnian 01 September 2013 (has links)
AimsHSPA12B is a newly discovered and endothelial-cell-specifically expressed heat shock protein. We have reported recently that overexpression of HSPA12B increased endothelial nitric oxide synthase (eNOS) expression in mouse cardiac tissues during endotoxemia. Endothelial NOS has been shown to protect heart from ischaemic injury. We hypothesized that overexpression of HSPA12B will attenuate cardiac dysfunction and remodelling after myocardial infarction (MI) through an eNOS-dependant mechanism.Methods and resultsMI was induced by permanent ligation of the left anterior descending coronary artery in the transgenic mice (Tg) overexpressing hspa12b gene and its wild-type (WT) littermates. Echocardiographic analysis revealed that Tg mice exhibited improvements in cardiac dysfunction and remodelling at 1 and 4 weeks after MI. These improvements were accompanied by a significant decrease in cardiomyocyte apoptosis and increase in capillary and arteriolar densities. Significant up-regulation of eNOS, VEGF, Ang-1, and Bcl-2 was also observed in Tg hearts compared with WT hearts after MI. However, pharmacological inhibition of eNOS abolished the HSPA12B-induced decrease in cardiomyocyte apoptosis and increase in capillary formation after MI. Most importantly, inhibition of eNOS abrogated the protection of HSPA12B against cardiac dysfunction and remodelling after MI.ConclusionsThese data demonstrate for the first time that the overexpression of HSPA12B attenuates cardiac dysfunction and remodelling after MI. This action of HSPA12B was mediated, at least in part, by prevention of cardiomyocyte apoptosis and promotion of myocardial angiogenesis via an eNOS-dependent mechanism. HSPA12B could be a novel target for the management of patients with post-MI cardiac dysfunction and remodelling.

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