RESUMO
OBJECTIVE: Mitral regurgitation (MR) developing concomitant with ischemic cardiomyopathy is a frequently diagnosed valvular lesion, for which an optimal therapeutic strategy is unknown. The contribution of MR to the ongoing cardiac remodeling from myocardial infarction (MI) remains controversial. We have developed a novel experimental model in which MI and severe MR can be independently introduced, to study the role of MR in chronic remodeling of the ischemic heart. METHODS: A total of 98 rats were induced with MI+MR (group 1), MI (group 2), MR (group 3), or sham surgery (group 4). MR was induced by inserting a needle into the anterior mitral leaflet via the ventricular apex in a beating heart. MI was induced by ligating the left coronary artery. Biweekly ultrasound examinations were performed after surgery, and invasive hemodynamic assessments were performed in some rats at 2, 10, and 20 weeks. RESULTS: At 2 weeks postsurgery, the mean end-diastolic volume was 432 ± 103 µL in ischemic hearts with MR, compared with 390 ± 76.3 µL in ischemic hearts without MR (a 10.76% difference). By 20 weeks, the mean volume was significantly greater in the former group (767 ± 246 µL vs 580 ± 85 µL; a 32.24% difference). At 2 weeks, mean end-systolic volume was 147 ± 46.8 µL in the ischemic hearts with MR and 147 ± 45.7 µL in those without MR. By 20 weeks, the mean volumes had increased to 357 ± 136.4 µL and 271 ± 82.3 µL, respectively (a 31.73% difference). CONCLUSIONS: MR in ischemic hearts significantly increased end-diastolic and end-systolic volumes of the left ventricle, indicating adverse cardiac remodeling and worse systolic function.
Assuntos
Insuficiência da Valva Mitral/fisiopatologia , Isquemia Miocárdica/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Remodelação Ventricular , Animais , Modelos Animais de Doenças , Ecocardiografia , Eletrocardiografia , Ligadura , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Mitral regurgitation (MR) imposes left ventricular volume overload, triggering rapid ventricular dilatation, increased myocardial compliance, and, ultimately, cardiac dysfunction. Breakdown of the extracellular matrix has been hypothesized to drive these rapid changes, partially from an imbalance in the matrix metalloproteinases (MMPs) and their tissue inhibitors [tissue inhibitors of metalloproteinase (TIMPs)]. In the present study, we developed a rat model of severe MR that mimics the human condition and investigated the temporal changes in extracellular matrix-related genes, collagen biosynthesis proteins, and proteolytic enzymes over a 20-wk period. Male Sprague-Dawley rats were anesthetized to a surgical plane with mechanical ventilation, and a thoracotomy was performed to expose the apex. Using transesophageal ultrasound guidance, a needle was inserted into the beating heart to perforate the anterior mitral leaflet and create severe MR. Animals were survived for 20 wk, with some animals terminated at 2, 10, and 20 wk for analysis of left ventricular tissue. A sham group that underwent the same surgery without mitral leaflet perforation and MR were used as controls. At 2 wk post-MR, increased collagen gene expression was measured, but protein levels of collagen did not corroborate this finding. In parallel, MMP-1-to-TIMP-4, MMP-2-to-TIMP-1, and MMP-2-to-TIMP-3 ratios were significantly elevated, indicating a proteolytic milieu in the myocardium, possibly causing collagen degradation. By 20 wk, many of the initial differences seen in the proteolytic ratios were not observed, with an increase in collagen compared with the 2-wk time point. Altogether, this data indicates that an imbalance in the MMP-to-TIMP ratio may occur early and potentially contribute to the early dilatation and compliance observed structurally. NEW & NOTEWORTHY In this rodent model of severe mitral regurgitation that mimics the human condition, eccentric left ventricular dilatation occurred rapidly and persisted over the 20-wk period with parallel changes in myocardial collagen and matrix metalloproteinases that may drive the extracellular matrix breakdown.
Assuntos
Colágeno/metabolismo , Ventrículos do Coração/enzimologia , Metaloproteinases da Matriz/metabolismo , Insuficiência da Valva Mitral/enzimologia , Miocárdio/enzimologia , Inibidores Teciduais de Metaloproteinases/metabolismo , Função Ventricular Esquerda , Remodelação Ventricular , Animais , Colágeno/genética , Modelos Animais de Doenças , Ecocardiografia Transesofagiana , Regulação da Expressão Gênica , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Masculino , Metaloproteinases da Matriz/genética , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/genética , Insuficiência da Valva Mitral/fisiopatologia , Ratos Sprague-Dawley , Índice de Gravidade de Doença , Fatores de Tempo , Inibidores Teciduais de Metaloproteinases/genéticaRESUMO
Se determinó la prevalencia de infección intestinal con helmintos en 461 perros en 2 períodos de tiempo, con la finalidad de evaluar el potencial zoonótico de los perros callejeros en Ciudad de La Habana. Los helmintos identificados fueron: Ancylostoma spp. en 97 animales (21,04 por ciento); Dipylidium caninum en 75 (16,26 por ciento) y Toxocara canis en 91 (19,73 por ciento). Las infecciones con Ancylostoma spp. tuvieron una frecuencia mayor en la estación de lluvia, mayo-octubre de 2005 (p< 0,01); mientras que D. caninum fue más común en la estación seca, noviembre-abril de 2006 (p< 0,01). T. canis fue más prevalente en animales jóvenes (< 1 año), mientras que en adultos (> 1 año) fueron Ancylostoma spp. y D. caninum. En cuanto al sexo, las perras hembras estaban más parasitadas por T. canis, mientras que D. caninum fue más frecuente en los machos. La asociación parasitaria que más se observó fue A. caninum y T. canis. Estos resultados permitieron un conocimiento actualizado sobre las principales especies de helmintos que afectan a los perros callejeros y algunas características de estas infecciones, que sirve de alerta sobre este potencial zoonótico.
The objective of the present study was to evaluate the zoonotic potential of the 461 stray dogs from the City of Havana, as well as, the prevalence of intestinal helminth infection in two periods. The identified helminths were Ancylostoma spp. in 97 dogs (21.04 percent), Dipylidium caninum in 75 (16.26 percent). and Toxocara canis in 91 dos (19.73 percent). Ancylostoma spp. infections were the most frequent in the rainy season,that is, May to October, 2005 (p< 0.01) whereas D. caninum was more common in the dry season, that is, November to April, 2006. (p< 0.01). T. canis was more prevalent in young animals (< 1 year), but in older dogs(> 1 year) were Ancylostoma spp. and D. caninum. Female dogs were more infected by T. canis, and D. caninum was more frequent in males. The most observed association was A. caninum -T. canis. These results allowed updating knowledge about helminth species affecting stray dogs and some characteristics of these infections, all of which can serve as a warning about this zoonotic potential.
Assuntos
Animais , Cães , Enteropatias Parasitárias/epidemiologiaRESUMO
The objective of the present study was to evaluate the zoonotic potential of the 461 stray dogs from the City of Havana, as well as, the prevalence of intestinal helminth infection in two periods. The identified helminths were Ancylostoma spp. in 97 dogs (21, 04%), Dipylidium caninum in 75 (16, 26%). and Toxocara canis in 91 dos (19, 73%). Ancylostoma spp. infections were the most frequent in the rainy season, that is, May to October, 2005 (P < 0,01) whereas D. caninum was more common in the dry season, that is, November to April, 2006. (p < 0,01). T. canis was more prevalent in young animals (< 1 year), but in older dogs (> 1 year) were Ancylostoma spp. and D. caninum. Female dogs were more infected by T. canis, and D. caninum was more frequent in males. The most observed association was A. caninum--T. canis. These results allowed updating knowledge about helminth species affecting stray dogs and some characteristics of these infections, all of which can serve as a warning about this zoonotic potential.