title: N,N'-diacetylchitobiose, an inhibitor of lysozyme, reverses myocardial depression and lessens norepinephrine requirements in Escherichia coli sepsis in dogs.
abstract: 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.
authors: Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada. minksn@cc.umanitoba.ca
authors: Steven N
authors: SN
authors: Mink
authors: Krika
authors: K
authors: Kasian
authors: Hans
authors: H
authors: Jacobs
authors: Zhao-Qin
authors: ZQ
authors: Cheng
authors: R Bruce
authors: RB
authors: Light
mesh_terms: D000818:Animals; D016470:Bacteremia / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D004187:Disaccharides / Q000494:pharmacology*; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D009113:Muramidase / Q000037:antagonists & inhibitors*; D009638:Norepinephrine / Q000494:pharmacology*; D012772:Shock, Septic / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D013318:Stroke Volume / Q000187:drug effects; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D004187:Disaccharides; D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D014662:Vasoconstrictor Agents; C010913:N,N-diacetylchitobiose; D009113:Muramidase; D009638:Norepinephrine