title: Prevention of cardiovascular effects of endotoxaemia by monoclonal antibodies specific for core endotoxin.
abstract: Passive immunization with antibody to the core region of endotoxin (core lipopolysaccharide (LPS)) has been reported to reduce mortality in severe sepsis. A rat model of endotoxaemia that reproduces the hyperdynamic cardiovascular state seen in early sepsis was developed to test monoclonal antibodies specific for core LPS. A thermodilution technique of measuring cardiac output was adapted for use in rats. Twenty-five animals were anaesthetized and mechanically ventilated with monitoring of central venous pressure and mean arterial pressure. Fluid replacement was adjusted to maintain the central venous pressure. Controls (n = 10) and antibody-treated animals (n = 5) showed no significant change in cardiac output. Animals given 0.1 mg kg-1 R2 endotoxin over 1 h (n = 5) showed a significant rise in cardiac output of 65 per cent (P < 0.01). This was abolished in rats given both antibody and endotoxin (n = 5). This study provides evidence that a monoclonal antibody against core LPS abolishes the hyperdynamic state induced by endotoxin infusion.
authors.affiliation: University Department of Surgery, Western Infirmary, Glasgow, UK.
authors.forename: J
authors.initials: J
authors.lastname: Reidy
authors.forename: I
authors.initials: I
authors.lastname: Wright
authors.forename: S J
authors.initials: SJ
authors.lastname: Boom
authors.forename: R
authors.initials: R
authors.lastname: Barclay
authors.forename: F
authors.initials: F
authors.lastname: Di Padova
authors.forename: G
authors.initials: G
authors.lastname: Ramsay
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects*; D004195:Disease Models, Animal; D004731:Endotoxins / Q000276:immunology / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014115:Toxemia / Q000517:prevention & control
chemical_list: D000911:Antibodies, Monoclonal; D004731:Endotoxins; D008070:Lipopolysaccharides; C042058:core endotoxin