Lipopolysaccharide and cytokines inhibit rat cardiomyocyte contractility in vitro

Autor: Deborah A. Siwik, Ion A. Hobai, Wilson S. Colucci, Justin C. Morse
Rok vydání: 2015
Předmět:
Zdroj: Journal of Surgical Research. 193:888-901
ISSN: 0022-4804
DOI: 10.1016/j.jss.2014.09.015
Popis: Background Sepsis-induced cardiomyopathy (SIC) is thought to be the result of detrimental effects of inflammatory mediators on the cardiac muscle. Here we studied the effects of prolonged (24 ± 4 h) exposure of adult rat ventricular myocytes (ARVM) to bacterial lipopolysaccharide (LPS) and inflammatory cytokines tumor necrosis factor (TNF) and interleukins-1 (IL-1) and IL-6. Materials and methods We measured sarcomere shortening (SS) and cellular calcium (Ca 2+ ) transients (ΔCa i , with fura-2 AM) in isolated cardiomyocytes externally paced at 5 Hz at 37°C. Results SS decreased after incubation with LPS (100 μg/mL), IL-1 (100 ng/mL), and IL-6 (30 ng/mL), but not with lesser doses of these mediators, or TNF (10–100 ng/mL). A combination of LPS (100 μg/mL), TNF, IL-1, and IL-6 (each 100 ng/mL; i.e., “Cytomix-100”) induced a maximal decrease in SS and ΔCa i . Sarcoplasmic reticulum (SR) Ca 2+ load (Ca SR , measured with caffeine) was unchanged by Cytomix-100; however, SR fractional release (ΔCa i /Ca SR ) was decreased. Underlying these effects, Ca 2+ influx into the cell (via L-type Ca 2+ channels, LTCC) and Ca 2+ extrusion via Na + /Ca 2+ exchange were decreased by Cytomix-100. SR Ca 2+ pump (SERCA) (SR Ca 2+ ATPase) was not affected. Conclusions Prolonged exposure of ARVM to a mixture of LPS and inflammatory cytokines inhibits cell contractility. The effect is mediated by the inhibition of Ca 2+ influx via LTCC, and partially opposed by the inhibition of Na + /Ca 2+ exchange. Because both mechanisms are commonly seen in animal models of SIC, we conclude that prolonged challenge with Cytomix-100 of ARVM may represent an accurate in vitro model for SIC.
Databáze: OpenAIRE
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