Lysozyme: a mediator of myocardial depression and adrenergic dysfunction in septic shock in dogs

N,N′,N′-triacetylglucosamine, an inhibitor of lysozyme, prevents myocardial depression in Escherichia coli sepsis in dogs*

“…The dose of TAC used in the pretreatment study was based on calculations previously obtained from the ventricular trabecular experiments, in which it was estimated that a plasma concentration of Ն10 Ϫ5 M would be required to inhibit lysozyme's depressant activity in vivo (5). Based on the molecular weight of TAC (628 molecular weight), the average size of the dog (20 kg), and the estimated distribution space of approximately 50% of total body weight, the dose chosen was 100 mg (Sigma Corporation Canada, Oakville, Ontario) mixed in 200 mL of 5% dextrose in water (D 5 W) that was given intravenously over 0.5 hrs.…”

“…The right ventricular trabecular preparation used in this study has also been described (5,12). Briefly, mongrel dogs (3-10 kg) were anesthetized with pentobarbital.…”

“…Plasma lysozyme is believed to stem mainly from disintegrating neutrophilic granulocytes and monocytes, and the high concentrations that are found in bone marrow, lung, spleen, and intestine have been suggested to relate to the breakdown of leukocytes located in these organs (9 -11). We hypothesize that Lzm-S binds to or hydrolyzes a cardiac surface glycoprotein that in turns leads to myocardial dysfunction in sepsis (see Discussion) (5). Furthermore, we use the term Lzm-S rather than lysozyme c, since from the standpoint of the present study, lysozyme c could have arisen from the source organ (i.e., the spleen or leukocytes arising from that organ) or possibly from other organs.…”

“…Some investigators have attributed this depression to mediators released as part of the inflammatory reaction (2)(3)(4). In a recent study, we identified a myocardial depressant factor in an Escherichia coli model of septic shock in dogs (5). We used a right ventricular trabecular preparation as a bioassay to identify the plasma fraction where myocardial depressant activity could be identified.…”

“…Once the nature of this myocardial depressant factor was identified, we showed in the right ventricular trabecular preparation that purified Lzm-S from canine spleen could be blocked by a competitive inhibitor of lysozyme N,N',NЉ-triacetylglucosamine, also referred to as N,N',NЉ-triacetylchitotriose (TAC) or chitotriose (5,8). TAC is the trisaccharide of NAG that has three NAG residues linked by ␤ (1-4) glycosidic linkages and competitively inhibits the enzymatic activity of Lzm-S.…”