acp-196 and Heart-Diseases

Sepsis is one of the most prevalent diseases in the world. The development of cardiac dysfunction in sepsis results in an increase of mortality. It is known that Bruton's tyrosine kinase (BTK) plays a role in toll-like receptor signaling and NLRP3 inflammasome activation, two key components in the pathophysiology of sepsis and sepsis-associated cardiac dysfunction. In this study we investigated whether pharmacological inhibition of BTK (ibrutinib 30 mg/kg and acalabrutinib 3 mg/kg) attenuates sepsis associated cardiac dysfunction in mice. 10-week old male C57BL/6 mice underwent CLP or sham surgery. One hour after surgery mice received either vehicle (5% DMSO + 30% cyclodextrin i.v.), ibrutinib (30 mg/kg i.v.), or acalabrutinib (3 mg/kg i.v.). Mice also received antibiotics and an analgesic at 6 and 18 h. After 24 h, cardiac function was assessed by echocardiography

Topics: Adenine; Agammaglobulinaemia Tyrosine Kinase; Animals; Benzamides; Cecum; Disease Models, Animal; Heart; Heart Diseases; Inflammasomes; Ligation; Male; Mice; Mice, Inbred C57BL; Piperidines; Protein Kinase Inhibitors; Punctures; Pyrazines; Pyrazoles; Pyrimidines; Sepsis