LAUSR

HighlightsMechanism for SIMD.Relies on PI3K/AKT pathway.PI3K might be a therapeutic target. Abstract A key component during sepsis is the phosphoinositide 3‐kinase (PI3K)/protein kinase B (Akt) signaling pathway, of which the PI3K‐&ggr; isoform is a major regulator in many inflammatory responses. However, the role of PI3K‐&ggr; in the development of sepsis‐induced myocardial dysfunction (SIMD) is unknown. In this study, we established a model of SIMD induced by lipopolysaccharide (LPS), subsequently used the selective inhibitor LY294002 and AS605240 to block the effect of PI3K and PI3K‐&ggr;, respectively. Cardiac function was evaluated by echocardiography, hearts were obtained for histological and protein expression examinations. ELISA was used to measure the serum levels of tumor necrosis factor alpha (TNF‐&agr;), interleukin‐6 (IL‐6), cardiac troponin I (cTnI) and heart‐type fatty acid binding protein (H‐FABP). LPS‐treated mice showed an increase to cardiac inflammation, myocardial damage and production of TNF‐&agr;, IL‐6, NF‐&kgr;B, cTnI and H‐FABP. Administration of AS605240 to LPS‐treated mice reduced some patho‐physiological characteristics of SIMD and reduced TNF‐&agr;, IL‐6, cTnI and H‐FABP production. However, administration of LY294002 did not improve those same conditions. The results showed that PI3K‐&ggr; is likely a crucial element in SIMD by regulating the PI3K/Akt pathway, and become a new marker of myocardial injury. Inhibition of PI3K‐&ggr; might be a potential therapeutic target in SIMD.