Efeito potencial cardioprotetor da espironolactona em coração isolado de rato

Detalhes bibliográficos
Autor(a) principal: Silva Neto, Julio Alves da
Data de Publicação: 2017
Tipo de documento: Trabalho de conclusão de curso
Idioma: por
Título da fonte: Repositório Institucional da UFS
Texto Completo: http://ri.ufs.br/jspui/handle/riufs/10587
Resumo: Spironolactone is a drug that have been widely used for many decades in clinical practice to heart failure treatment, often in association to digitalis. However, there are few reports about its effects directly in the heart tissue as well as the cardioprotection against digitalis toxicity. Thus, experimental protocols were carried out using isolated male rat hearts (Wistar) mounted in Langendorff apparatus perfused with Krebs-Henseleit nutrient solution (32 ± 0,5ºC) under constant flow (10 mL. mim-1) in wich were evaluated the acute effects of spironolactone (10 μmol L-1) to electrocardiographic parameters (ECG) and left ventricular pressure using a latex cuff inflated at 150 mmHg and coupled to transducer. Protocols were performed in absence or presence of potassium channels blockers as tetraethylammonium (20 m.mol L-1) or glibenclamide (100 μ.mol L-1) or ouabain (100 μ.mol L -1), an Na+/K+-ATPase inhibitor. Data shown that spironolactone have increased PR interval of ECG and reduced QT and QTc in same time without QRS duration change. To presence of potassium channel inhibitors, TEA showed, but no glibenclamide, the reduction of PRi lengthening spironolactone-induced, in same time, QT and QTc shortening promoted by spironolactone were reduced. Spironolactone rises the left ventricular pressure increased by ouabain and ameliorates the electrocardiographic changes ouabain-induced, such as QTi prolongation, bradycardia and fist degree blockade (PRi prolongation). Diastolic ventricular relaxation was improved to spironolactone presence while it is one of goals to heart failure treatment. The spirolonactone-induced contractile response is double: earliest is inotropic positive however reduces the left ventricular pressure along the perfusion. The first derivative of ventricular relaxation is reduced by spironolactone. Having in hands these data we can prove that spironolactone acts directly in the heart tissue shortening the ECG repolarization time by means of potassium currents facilitation and ameliorates the diastolic ventricular relaxation, also prevents alterations at ECG shape digitalis-induced without impairment its inotropic positive effect.
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spelling Silva Neto, Julio Alves daCarvalho, Antônio Paes de2019-02-25T13:08:09Z2019-02-25T13:08:09Z2017-03-22Silva Neto, Julio Alves da. Efeito potencial cardioprotetor da espironolactona em coração isolado de rato. São Cristóvão, SE, 2017. Monografia (graduação em Farmácia) – Departamento de Farmácia, Centro de Ciências Biológicas e da Saúde, Universidade Federal de Sergipe, São Cristóvão, 2017http://ri.ufs.br/jspui/handle/riufs/10587Spironolactone is a drug that have been widely used for many decades in clinical practice to heart failure treatment, often in association to digitalis. However, there are few reports about its effects directly in the heart tissue as well as the cardioprotection against digitalis toxicity. Thus, experimental protocols were carried out using isolated male rat hearts (Wistar) mounted in Langendorff apparatus perfused with Krebs-Henseleit nutrient solution (32 ± 0,5ºC) under constant flow (10 mL. mim-1) in wich were evaluated the acute effects of spironolactone (10 μmol L-1) to electrocardiographic parameters (ECG) and left ventricular pressure using a latex cuff inflated at 150 mmHg and coupled to transducer. Protocols were performed in absence or presence of potassium channels blockers as tetraethylammonium (20 m.mol L-1) or glibenclamide (100 μ.mol L-1) or ouabain (100 μ.mol L -1), an Na+/K+-ATPase inhibitor. Data shown that spironolactone have increased PR interval of ECG and reduced QT and QTc in same time without QRS duration change. To presence of potassium channel inhibitors, TEA showed, but no glibenclamide, the reduction of PRi lengthening spironolactone-induced, in same time, QT and QTc shortening promoted by spironolactone were reduced. Spironolactone rises the left ventricular pressure increased by ouabain and ameliorates the electrocardiographic changes ouabain-induced, such as QTi prolongation, bradycardia and fist degree blockade (PRi prolongation). Diastolic ventricular relaxation was improved to spironolactone presence while it is one of goals to heart failure treatment. The spirolonactone-induced contractile response is double: earliest is inotropic positive however reduces the left ventricular pressure along the perfusion. The first derivative of ventricular relaxation is reduced by spironolactone. Having in hands these data we can prove that spironolactone acts directly in the heart tissue shortening the ECG repolarization time by means of potassium currents facilitation and ameliorates the diastolic ventricular relaxation, also prevents alterations at ECG shape digitalis-induced without impairment its inotropic positive effect.A espironolactona é um medicamento usado há muitas décadas na prática clínica para o tratamento da insuficiência cardíaca em associação com os digitálicos cardiotônicos. No entanto, são escassos os estudos dos efeitos cardíacos diretos da espironolactona no coração assim como sua ação cardioprotetora frente à intoxicação digitálica. Para tanto, foram feitos experimentos em corações isolados de ratos machos (Wistar) montados em sistema de perfusão retrógrada de Langendorff, com solução nutriente de Krebs-Henseleit (32 ± 0,5ºC), sob fluxo constante (10 mL. mim-1). Foram avaliados os efeitos agudos da espironolactona (10 μ.mol. L-1) sobre os parâmetros eletrocardiográficos (ECG) e sobre a pressão ventricular esquerda (PVE) que foi determinada com auxílio de um balonete de látex inflado (150 mmHg) e acoplado a um transdutor de pressão. Os protocolos foram executados na ausência e na presença de drogas que inibem correntes de potássio: tetraetilamônio (20 m.mol. L-1) ou glibenclamida (100 μ.mol. L-1) e na presença da ouabaína (100 μ.mol. L-1), um inibidor da Na+/K+-ATPase. Os resultados mostraram que a espironolactona prolongou o intervalo PR do ECG, reduziu os intervalos QT e o QTc sem alterar a duração do complexo QRS. Na presença dos inibidores de canais para potássio foi observado que o TEA, mas não a glibenclamida, reduziu o prolongamento do PRi gerado pela espironolactona; ao mesmo tempo, observou-se que a redução do QT e QTc pela espironolactona foi atenuado na presença destes inibidores. A espironolactona potencializou o aumento da pressão ventricular esquerda e reduziu as alterações eletrocardiográficas induzidas pela ouabaína, tais como aumento do QTi e bradicardia. A espironolactona também melhorou a severidade da arritmia diminuindo o bloqueio atrioventricular (aumento do PRi) induzido pela ouabaína. Além disso, a espironolactona melhorou o relaxamento diastólico ventricular, que é uma das metas para o tratamento da insuficiência cardíaca. A resposta contrátil induzida pela espironolactona isoladamente é bifásica, ou seja, inicialmente é inotrópica positiva, contudo reduz a pressão ventricular esquerda com o decorrer da perfusão. A primeira derivada temporal de relaxamento do ventrículo também é reduzida pela espironolactona. Tendo em mãos estes dados, pode-se afirmar que a espironolactona atua diretamente no músculo cardíaco, apresentando um potencial cardioprotetor porque atua reduzindo o tempo de repolarização do ECG por facilitar correntes de potássio e melhora o relaxamento diastólico. Além disso, ela previne as alterações no ECG sem prejudicar a resposta inotrópica promovida pela ouabaína.São Cristóvão, SEporFarmáciaEnsino de farmáciaCardiografiaEspironolactonaCoraçãoCamundogosBiofísicaMamíferosCIENCIAS DA SAUDE::FARMACIAEfeito potencial cardioprotetor da espironolactona em coração isolado de ratoinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/bachelorThesisUniversidade Federal de SergipeDFA - Departamento de Farmácia – São Cristóvão - Presencialreponame:Repositório Institucional da UFSinstname:Universidade Federal de Sergipe (UFS)instacron:UFSinfo:eu-repo/semantics/openAccessTEXTJulio_Alves_Silva_Neto.pdf.txtJulio_Alves_Silva_Neto.pdf.txtExtracted texttext/plain84287https://ri.ufs.br/jspui/bitstream/riufs/10587/3/Julio_Alves_Silva_Neto.pdf.txte8baa93db6b0781817d73448f952ba44MD53THUMBNAILJulio_Alves_Silva_Neto.pdf.jpgJulio_Alves_Silva_Neto.pdf.jpgGenerated Thumbnailimage/jpeg1289https://ri.ufs.br/jspui/bitstream/riufs/10587/4/Julio_Alves_Silva_Neto.pdf.jpg2ad529c22555e34e8fe4d64b97f43ad7MD54LICENSElicense.txtlicense.txttext/plain; charset=utf-81475https://ri.ufs.br/jspui/bitstream/riufs/10587/1/license.txt098cbbf65c2c15e1fb2e49c5d306a44cMD51ORIGINALJulio_Alves_Silva_Neto.pdfJulio_Alves_Silva_Neto.pdfapplication/pdf913013https://ri.ufs.br/jspui/bitstream/riufs/10587/2/Julio_Alves_Silva_Neto.pdfb40e0a120183964f9aef154dfd977ea7MD52riufs/105872019-02-25 10:08:37.633oai:ufs.br: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Repositório InstitucionalPUBhttps://ri.ufs.br/oai/requestrepositorio@academico.ufs.bropendoar:2019-02-25T13:08:37Repositório Institucional da UFS - Universidade Federal de Sergipe (UFS)false
dc.title.pt_BR.fl_str_mv Efeito potencial cardioprotetor da espironolactona em coração isolado de rato
title Efeito potencial cardioprotetor da espironolactona em coração isolado de rato
spellingShingle Efeito potencial cardioprotetor da espironolactona em coração isolado de rato
Silva Neto, Julio Alves da
Farmácia
Ensino de farmácia
Cardiografia
Espironolactona
Coração
Camundogos
Biofísica
Mamíferos
CIENCIAS DA SAUDE::FARMACIA
title_short Efeito potencial cardioprotetor da espironolactona em coração isolado de rato
title_full Efeito potencial cardioprotetor da espironolactona em coração isolado de rato
title_fullStr Efeito potencial cardioprotetor da espironolactona em coração isolado de rato
title_full_unstemmed Efeito potencial cardioprotetor da espironolactona em coração isolado de rato
title_sort Efeito potencial cardioprotetor da espironolactona em coração isolado de rato
author Silva Neto, Julio Alves da
author_facet Silva Neto, Julio Alves da
author_role author
dc.contributor.author.fl_str_mv Silva Neto, Julio Alves da
dc.contributor.advisor1.fl_str_mv Carvalho, Antônio Paes de
contributor_str_mv Carvalho, Antônio Paes de
dc.subject.por.fl_str_mv Farmácia
Ensino de farmácia
Cardiografia
Espironolactona
Coração
Camundogos
Biofísica
Mamíferos
topic Farmácia
Ensino de farmácia
Cardiografia
Espironolactona
Coração
Camundogos
Biofísica
Mamíferos
CIENCIAS DA SAUDE::FARMACIA
dc.subject.cnpq.fl_str_mv CIENCIAS DA SAUDE::FARMACIA
description Spironolactone is a drug that have been widely used for many decades in clinical practice to heart failure treatment, often in association to digitalis. However, there are few reports about its effects directly in the heart tissue as well as the cardioprotection against digitalis toxicity. Thus, experimental protocols were carried out using isolated male rat hearts (Wistar) mounted in Langendorff apparatus perfused with Krebs-Henseleit nutrient solution (32 ± 0,5ºC) under constant flow (10 mL. mim-1) in wich were evaluated the acute effects of spironolactone (10 μmol L-1) to electrocardiographic parameters (ECG) and left ventricular pressure using a latex cuff inflated at 150 mmHg and coupled to transducer. Protocols were performed in absence or presence of potassium channels blockers as tetraethylammonium (20 m.mol L-1) or glibenclamide (100 μ.mol L-1) or ouabain (100 μ.mol L -1), an Na+/K+-ATPase inhibitor. Data shown that spironolactone have increased PR interval of ECG and reduced QT and QTc in same time without QRS duration change. To presence of potassium channel inhibitors, TEA showed, but no glibenclamide, the reduction of PRi lengthening spironolactone-induced, in same time, QT and QTc shortening promoted by spironolactone were reduced. Spironolactone rises the left ventricular pressure increased by ouabain and ameliorates the electrocardiographic changes ouabain-induced, such as QTi prolongation, bradycardia and fist degree blockade (PRi prolongation). Diastolic ventricular relaxation was improved to spironolactone presence while it is one of goals to heart failure treatment. The spirolonactone-induced contractile response is double: earliest is inotropic positive however reduces the left ventricular pressure along the perfusion. The first derivative of ventricular relaxation is reduced by spironolactone. Having in hands these data we can prove that spironolactone acts directly in the heart tissue shortening the ECG repolarization time by means of potassium currents facilitation and ameliorates the diastolic ventricular relaxation, also prevents alterations at ECG shape digitalis-induced without impairment its inotropic positive effect.
publishDate 2017
dc.date.issued.fl_str_mv 2017-03-22
dc.date.accessioned.fl_str_mv 2019-02-25T13:08:09Z
dc.date.available.fl_str_mv 2019-02-25T13:08:09Z
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dc.identifier.citation.fl_str_mv Silva Neto, Julio Alves da. Efeito potencial cardioprotetor da espironolactona em coração isolado de rato. São Cristóvão, SE, 2017. Monografia (graduação em Farmácia) – Departamento de Farmácia, Centro de Ciências Biológicas e da Saúde, Universidade Federal de Sergipe, São Cristóvão, 2017
dc.identifier.uri.fl_str_mv http://ri.ufs.br/jspui/handle/riufs/10587
identifier_str_mv Silva Neto, Julio Alves da. Efeito potencial cardioprotetor da espironolactona em coração isolado de rato. São Cristóvão, SE, 2017. Monografia (graduação em Farmácia) – Departamento de Farmácia, Centro de Ciências Biológicas e da Saúde, Universidade Federal de Sergipe, São Cristóvão, 2017
url http://ri.ufs.br/jspui/handle/riufs/10587
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