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Previous issue date: 2012-12-20 / Background: Erythropoietin (EPO) and granulocyte colony stimulating factor (GCSF) have generated interest as novel therapies after myocardial infarction (MI), but the effect of combination therapy has not been studied in the large animal model.Objetives: We investigated the impact of prolonged combination therapy with EPO and GCSF on cardiac function, infarct size, and vascular density after MI in a porcine model.Methods: MI was induced in pigs by a 90 min balloon occlusion of the left anterior descending coronary artery. 16 animals were treated with EPO+GCSF, or saline (control group). Cardiac function was assessed by echocardiography and pressure-volume measurements at baseline, 1 and 6 weeks post-MI. Histopathology was performed 6 weeks post-MI.Results: At week 6, EPO+GCSF therapy stabilized left ventricular ejection fraction, (41?1% vs. 33?1%, p<0.01) and improved diastolic function compared to the control group. Histopathology revealed increased areas of viable myocardium and vascular density in the EPO+GCSF therapy, compared to the control. Despite these encouraging results, in a historical analysis comparing combination therapy with monotherapy with EPO or GCSF, there were no significant additive benefits in the LVEF and volumes overtime using the combination therapy.Conclusion: Our findings indicate that EPO+GCSF combination therapy promotes stabilization of cardiac function after acute MI. However, combination therapy does not seem to be superior to monotherapy with either EPO or GCSF / Introdu??o: Recentemente, a eritropoetina (EPO) e o fator estimulante de col?nia de granul?citos (GCSF) surgiram como potenciais terapias no tratamento do infarto agudo do mioc?rdio (IAM). Contudo, os efeitos da terapia combinada ainda est?o por ser investigados.Objetivo: Investigar a efic?cia e seguran?a da terapia combinada com EPO e GCSF p?s-IAM em um modelo porcino.M?todos: IAM foi induzido em porcos dom?sticos atrav?s da oclus?o por 90 minutos da coron?ria descendente anterior esquerda. Dezesseis animais foram tratados com an?logo de longa a??o da EPO a GCSF ou solu??o salina (grupo controle). Fun??o card?aca foi avaliada via ecocardiografia e medidas de press?o-volume no inicio do estudo, uma e seis semanas ap?s o IM. Histologia foi realizada seis semanas ap?s o IAM.Resultados: Seis semanas ap?s o IAM, a terapia combinada com EPO e GCSF demonstrou estabilizar a fra??o de eje??o ventricular esquerda (41?1% vs. 33?1%, p<0.01) e melhorar a fun??o diast?lica quando comparada com o grupo controle. Avalia??o histopatol?gica revelou aumento de ?reas de mioc?rdio vi?vel e de densidade vascular no grupo tratado com EPO e GCSF quando comparada com o grupo controle. Apesar dos resultados encorajadores, em uma avalia??o hist?rica comparando a terapia combinada com a monoterapia com EPO ou GCSF, a terapia combinada n?o demonstrou ter beneficio adicional na preserva??o da fra??o de eje??o ou volumes ventriculares ao longo do per?odo em estudo.Conclus?o: Os presentes achados sugerem que a terapia combinada com EPO e GCSF promove a estabiliza??o da fun??o card?aca ap?s o IAM. Contudo, a terapia combinada n?o aprece ser superior a monoterapia com EPO ou GCSF
| Identifer | oai:union.ndltd.org:IBICT/oai:tede2.pucrs.br:tede/1717 |
| Date | 20 December 2012 |
| Creators | Angeli, Franca Stedile |
| Contributors | Bodanese, Luiz Carlos |
| Publisher | Pontif?cia Universidade Cat?lica do Rio Grande do Sul, Programa de P?s-Gradua??o em Medicina e Ci?ncias da Sa?de, PUCRS, BR, Faculdade de Medicina |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
| Format | application/pdf |
| Source | reponame:Biblioteca Digital de Teses e Dissertações da PUC_RS, instname:Pontifícia Universidade Católica do Rio Grande do Sul, instacron:PUC_RS |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 7620745074616285884, 500, 600, -8624664729441623247 |
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