Artículo
Toll-like receptor 4 and nlrp3 caspase 1-interleukin-1b-axis are not involved in colon ascendens stent peritonitis-associated heart disease
López Alarcón, Maria Micaela; Fernandez Ruocco, Maria Julieta; Ferreira, Fabiano; Paula Neto, Heitor A.; Sepúlveda, Marisa Noemí
; Vila Petroff, Martin Gerarde
; Carvalho, Adriana Bastos; Ramos, Isalira Peroba; Branda, Hugo Justino; Paiva, Claudia N.; Medei, Emiliano
Fecha de publicación:
10/2018
Editorial:
Lippincott Williams
Revista:
Shock
ISSN:
1073-2322
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Hemodynamic collapse and myocardial dysfunction are among the major causes of death in severe sepsis. The purpose of this study was to assess the role played by toll-like receptor 4 and by the NLRP3 inflammasome in the cardiac dysfunction that occurs after high-grade polymicrobial sepsis. We performed the colon ascendens stent peritonitis (CASP) surgery in Tlr4-/-, Nlrp3-/-, and caspase-1-/- mice. We also assessed for the first time the electrical heart function in the colon ascendens stent peritonitis (CASP) model. The QJ interval was increased in wild-type C57BL/6J mice after CASP when compared with sham controls, a result paralleled by an increase in the cardiac action potential (AP) duration (APD). The decreases in ejection fraction (EF), left ventricle end diastolic volume, stroke volume, and cardiac output found after CASP were similar among all groups of mice. Similar heart response was found when Nlrp3-/- mice were submitted to highgrade cecal ligation and puncture. Despite developing cardiac dysfunction similar to wild types after CASP, Nlrp3-/- mice had reduced circulating levels of interleukin (IL)-1b, IL-6 and tumor necrosis factor-α. Our results demonstrate that the genetic ablation of Tlr4, Nlrp3, and caspase-1 does not prevent the cardiac dysfunction, despite preventing the increase in pro-inflammatory cytokines, indicating that these are not feasible targets to therapy in high-grade sepsis.
Palabras clave:
Cardioimmunology
,
Electrophysiology
,
Innate Immunology
,
Interleukin-1b
,
Sepsis
Archivos asociados
Licencia
Identificadores
Colecciones
Articulos(CCT - LA PLATA)
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - LA PLATA
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - LA PLATA
Articulos(CIC)
Articulos de CENTRO DE INVEST.CARDIOVASCULARES (I)
Articulos de CENTRO DE INVEST.CARDIOVASCULARES (I)
Citación
López Alarcón, Maria Micaela; Fernandez Ruocco, Maria Julieta; Ferreira, Fabiano; Paula Neto, Heitor A.; Sepúlveda, Marisa Noemí; et al.; Toll-like receptor 4 and nlrp3 caspase 1-interleukin-1b-axis are not involved in colon ascendens stent peritonitis-associated heart disease; Lippincott Williams; Shock; 50; 4; 10-2018; 483-492
Compartir
Altmétricas