Question:

To better understand molecular mechanisms during septic myocardial dysfunction we analysed the NADPH oxidases, NO-synthases (NOS) as well as matrix metalloproteinase (MMP) subunits which potentially leads to a myocardial damage in septic mice.

Methods:

Animal models with peritoneal contamination and infection (PCI), ELISA, real-time RT-PCR, immunohistochemistry (IHC) and zymography were used.

Results:

Serum samples of mice with induced peritoneal sepsis and septic myocardial dysfunction showed an increased level of Procalcitonin as well as cardiac Troponin I after 6 hours in comparison to sham individuals. In parallel elevated levels of Tumor necrosis factor alpha (TNF alpha), Interleukin 1 beta (IL-1 beta) and Interferon gamma (INF gamma) were observed in the serum of mice at 6 hours after sepsis induction using the PCI model. Real-time RT-PCR analysis further showed a significant up-regulation of NOX2 transcripts and a significant down-regulation of the NOS2 isoform in septic heart of mice which leads to an increased level of detectable Reactive Oxygen Species (ROS). These findings were paralleled by an up-regulation of transcripts of the MMP isoforms 1 and 3 and a down-regulation of MMP2. Further an increased MMP protease activity which was measured by zymography was evaluated in the lysate of septic heart from mice. We suggest a potential signaling pathway activating MMP isoforms during septic myocardial dysfunction including the TLR-4 receptor which was observed in capillaries of IHC sections of septic heart from mice.

Conclusion:

We constitute an increased ROS production as well as a defined increase of MMP isoforms potentially mediated through a TLR-4 depending mechanism as typical characteristic changes during septic myocardial dysfunction of mice.