Disctinct mechanisms for diastolic dysfunction in diabetes mellitus and pressure-overload.

• Tipo: Resumo de Comunicação em Conferência Nacional
• Data: 2010

Autores

Falcão-Pires I (Autor) FMUP; Gonçalves D (Autor) Outra; Moreira-Gonçalves D (Autor) Outra; Leite-Moreira AF (Autor) FMUP

Ata de Conferência Nacional

Título: Revista Portuguesa Cardiologia

Página Inicial: I-29

XXXI Congresso Português de Cardiologia

Lisboa, 09 a 12 de Abril de 2010

Classificação Científica

FOS: Ciências médicas e da saúde > Outras ciências médicas

CORDIS: Ciências da Saúde > Ciências Médicas > Medicina > Cardiologia

Outras Informações

Resumo (PT): We aimed to characterize the changes in myocardial structure and function induced by two frequent co-existing causes of diastolic heart failure, chronic pressure-overload and diabetes mellitus. Pressure-overload was established in rats by supra-renal aortic banding. Six weeks later, diabetes was induced by streptozotocin (65mg/kg,ip), resulting in 4 groups: SHAM, banded( BA), diabetic(DM) and diabetic-banded(DB). Twelve-weeks later, pressure-volume loops were obtained and left ventricular samples were collected to evaluate extracelular matrix alterations and myofilaments function and phosphorylation. Compared to SHAM, pressure-overload increased cardiomyocytes diameter (MyD, BA: 22.0±0.4Ìm, SHAM: 18.2±0.3Ìm) and myofilament maximal-force (BA: 25.7±3.6kN/m2, SHAM: 18.6±1.4kN/m2), Ca2+-sensitivity (BA: 5.56±0.02, SHAM: 5.50±0.02) and MyBP-C phosphorylation, while decreasing rate of force-redevelopment (Ktr; BA: 14.9±1.1s-1, SHAM: 25.2±1.5s-1). At the extracellular matrix level, fibrosis (BA: 10.8±0.9%, SHAM: 5.3±0.6%), pro-MMP-2 and MMP-9 activity increased and, in vivo, relaxation was impaired (t; BA:14.0±0.9ms, SHAM: 12.9±0.4ms). Diabetes increased MyD (DM:21.4±0.4Ìm, DB:20.6±0.4Ìm), fibrosis (DM:13.9±1.8%, DB:13.8±0.8%), advanced glycation end-products deposition (DM: 4.9±0.6score/mm2, DB:5.1±0.4 score/mm2, SHAM:2.1±0.3score/mm2), Ca2+-sensitivity (DM:5.57±0.02, DB:5.57±0.01) and TIMP-1 concentration, while decreased Ktr (DM: 13.5±1.9s-1, DB:15.2±1.4s-1) and MMP-9/TIMP- 1 ratio. Diabetic hearts were stiffer (higher end-diastolic-pressure: DM:7.0±1.2mmHg, DB:6.7±0.7mmHg, SHAM:5.3±0.4mmHg; steeper end-diastolic-pressure-volume relation: DM:0.59±0.18, DB:0.83±0.17, SHAM: 0.41±0.10), and hypo-contractile (decreased heart rate and cardiac output). The association of diabetes and pressure-overload combined relaxation abnormalities and increased stiffness inducing further pulmonary congestion (Lungs/body-weight; DB:5.23±0.21g/Kg, SHAM: 3.80±0.14g/Kg). Diabetes mellitus and pressure overload led to distinct diastolic dysfunction (DD) phenotypes: while diabetes promoted myocardial stiffening, pressure overload impaired relaxation. Their association amplified these damages in a way that precipitates to a faster progression to heart failure.

Idioma: Português

Tipo (Avaliação Docente): Científica

Notas: XXXI Congresso Português de Cardiologia, publicado na Rev. Port. Cardiol. 2010; Vol.29(Supl.I):I-29.