Lipoteichoic acid from Staphylococcus aureus directly affects cardiomyocyte contractility and calcium transients.
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 1h 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 24h-exposure to LTA.
Institute of Molecular and Cell Physiology, Hannover Medical School, Germany.
Natalie
N
Mutig
Cornelia
C
Geers-Knoerr
Birgit
B
Piep
Aanchal
A
Pahuja
Peter M
PM
Vogt
Bernhard
B
Brenner
Andreas D
AD
Niederbichler
Theresia
T
Kraft
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012518:Sarcomeres / Q000187:drug effects* / Q000502:physiology; D018805:Sepsis / Q000378:metabolism / Q000503:physiopathology; D059010:Single-Cell Analysis / Q000379:methods; D013211:Staphylococcus aureus / Q000378:metabolism; D013682:Teichoic Acids / Q000378:metabolism / Q000494:pharmacology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D008070:Lipopolysaccharides; D013682:Teichoic Acids; D014409:Tumor Necrosis Factor-alpha; C009900:lipoteichoic acid; D002118:Calcium
Cardiac depression; Langendorff preparation; Sarcomere shortening analysis; Sepsis; Septic cardiomyopathy