Open AccessToll-Like Receptor 4 and NLRP3 Caspase 1- Interleukin-1β-Axis are Not Involved in Colon Ascendens Stent Peritonitis-Associated Heart Disease
Author(s) -
María Micaela López Alarcón,
Julieta Fernández Ruocco,
Fabiano Ferreira,
Heitor A. Paula-Neto,
Marisa Noemí Sepúlveda,
Martin Petroff,
Adriana Bastos Carvalho,
Isalira Peroba Ramos,
Hugo Justino Branda,
Cláudia N. Paiva,
Emiliano Medei
Publication year - 2018
Publication title -
shock
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.095
H-Index - 117
eISSN - 1540-0514
pISSN - 1073-2322
DOI - 10.1097/shk.0000000000001059
Subject(s) - peritonitis , medicine , toll , toll like receptor , interleukin , trif , receptor , immunology , innate immune system , cytokine
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 high-grade cecal ligation and puncture. Despite developing cardiac dysfunction similar to wild types after CASP, Nlrp3 mice had reduced circulating levels of interleukin (IL)-1β, 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.