• Ralph Lohner, Markus Schwederski, Carolin Narath, Johanna Klein, Georg D Duerr, Alexandra Torno, Pascal Knuefermann, Andreas Hoeft, Georg Baumgarten, Rainer Meyer, and Olaf Boehm.
• Institute for Physiology II, University of Bonn, Nussallee 11, 53115 Bonn, Germany.
• Mediators Inflamm. 2013 Jan 1;2013:261049.

BackgroundAim was to elucidate the role of toll-like receptor 9 (TLR9) in cardiac inflammation and septic heart failure in a murine model of polymicrobial sepsis.MethodsSepsis was induced via colon ascendens stent peritonitis (CASP) in C57BL/6 wild-type (WT) and TLR9-deficient (TLR9-D) mice. Bacterial load in the peritoneal cavity and cardiac expression of inflammatory mediators were determined at 6, 12, 18, 24, and 36 h. Eighteen hours after CASP cardiac function was monitored in vivo. Sarcomere length of isolated cardiomyocytes was measured at 0.5 to 10 Hz after incubation with heat-inactivated bacteria.ResultsCASP led to continuous release of bacteria into the peritoneal cavity, an increase of cytokines, and differential regulation of receptors of innate immunity in the heart. Eighteen hours after CASP WT mice developed septic heart failure characterised by reduction of end-systolic pressure, stroke volume, cardiac output, and parameters of contractility. This coincided with reduced cardiomyocyte sarcomere shortening. TLR9 deficiency resulted in significant reduction of cardiac inflammation and a sustained heart function. This was consistent with reduced mortality in TLR9-D compared to WT mice.ConclusionsIn polymicrobial sepsis TLR9 signalling is pivotal to cardiac inflammation and septic heart failure.

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