Cardiovascular dysfunction in
septic shock (SS) is ascribed to the release of inflammatory mediators.
Norepinephrine (NE) is often administered to treat low MAP in SS. We recently found that
lysozyme c (Lzm-S) released from leukocytes was a mediator of myocardial depression in an Escherichia coil model of SS in dogs. This effect can be blocked in an in vitro preparation by
chitobiose, a competitive inhibitor of Lzm-S. In the present study, we examined whether
chitobiose treatment can reverse myocardial depression and obviate NE requirements in two respective canine E. coli preparations. In a 6-h study, we administered
chitobiose after 3.5 h of E. coli
bacteremia and compared
stroke work (SW) and MAP at 6 h with a
sepsis control group. In a 12-h study, we determined whether
chitobiose treatment can reduce the need for NE requirements during 12 h of
bacteremia. In the latter study, either
chitobiose or NE was given when MAP decreased approximately 20% from the presepsis value in respective groups. In anesthetized, mechanically ventilated dogs, we monitored hemodynamic parameters during continuous E. coli infusion. In the 6-h study,
chitobiose improved SW and MAP at the 6-h period as compared with the nontreated
sepsis group. In the 12-h study, SW and MAP increased after
chitobiose without the necessity of NE administration. These results suggest that inhibitors of Lzm-S such as
chitobiose may improve myocardial depression and reduce the need for NE requirements in SS.