期刊
MOLECULAR IMMUNOLOGY
卷 56, 期 4, 页码 720-728出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2013.07.007
关键词
Sepsis; Septic cardiomyopathy; Cardiac depression; Langendorff preparation; Sarcomere shortening analysis
资金
- Deutsche Forschungsgemeinschaft [KR 1187/19-1]
- Hannover Medical School
- internal StrucMed program
Lipoteichoic acid (LTA) is the key pathogenic factor of gram-positive bacteria and contributes significantly to organ dysfunction in sepsis, a frequent complication in critical care patients. We hypothesized that LTA directly affects cardiomyocyte function, thus contributing to cardiac failure in sepsis. This study was designed to evaluate the effects of LTA on contractile properties and calcium-transients of isolated adult rat cardiomyocytes. When myocytes were exposed to LTA for 1 h prior to analysis, the amplitudes of calcium-transients as well as sarcomere shortening increased to 130% and 142% at 1 Hz stimulation frequency. Relengthening of sarcomeres as well as decay of calcium-transients was accelerated after LTA incubation. Exposure to LTA for 24 h resulted in significant depression of calcium-transients as well as of sarcomere shortening compared to controls. One of the major findings of our experiments is that LTA most likely affects calcium-handling of the cardiomyocytes. The effect is exacerbated by reduced extracellular calcium, which resembles the clinical situation in septic patients. Functionally, an early stimulating effect of LTA with increased contractility of the cardiomyocytes may be an in vitro reflection of early hyperdynamic phases in clinical sepsis. Septic disorders have been shown to induce late hypodynamic states of the contractile myocardium, which is also supported at the single-cell level in vitro by results of our 24 h-exposure to LTA. (C) 2013 Elsevier Ltd. All rights reserved.
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