Prevention of cardiovascular effects of endotoxaemia by monoclonal antibodies specific for core endotoxin

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.

[1]  I. Schedel,et al.  Treatment of gram-negative septic shock with an immunoglobulin preparation: a prospective, randomized clinical trial. , 1993 .

[2]  Jerome J. Schentag,et al.  A Controlled Clinical Trial of E5 Murine Monoclonal IgM Antibody to Endotoxin in the Treatment of Gram-Negative Sepsis , 1991 .

[3]  M. A. Martin,et al.  A controlled clinical trial of E5 murine monoclonal IgM antibody to endotoxin in the treatment of gram-negative sepsis. The XOMA Sepsis Study Group. , 1991, JAMA.

[4]  C. Sprung,et al.  Treatment of gram-negative bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin. A randomized, double-blind, placebo-controlled trial. The HA-1A Sepsis Study Group. , 1991 .

[5]  D G Altman,et al.  Analysis of serial measurements in medical research. , 1990, BMJ.

[6]  J. Hassett,et al.  The Gut Origin Septic States in Blunt Multiple Trauma (ISS = 40) in the ICU , 1987, Annals of surgery.

[7]  D. Altman,et al.  STATISTICAL METHODS FOR ASSESSING AGREEMENT BETWEEN TWO METHODS OF CLINICAL MEASUREMENT , 1986, The Lancet.

[8]  J. McCutchan,et al.  PREVENTION OF GRAM-NEGATIVE SHOCK AND DEATH IN SURGICAL PATIENTS BY ANTIBODY TO ENDOTOXIN CORE GLYCOLIPID , 1985, The Lancet.

[9]  S. Gaffin,et al.  ANTI-LIPOPOLYSACCHARIDE IMMUNOTHERAPY IN MANAGEMENT OF SEPTIC SHOCK OF OBSTETRIC AND GYNAECOLOGICAL ORIGIN , 1984, The Lancet.

[10]  J. Fierer,et al.  Treatment of gram-negative bacteremia and shock with human antiserum to a mutant Escherichia coli. , 1982, The New England journal of medicine.

[11]  T Sato,et al.  Measurement of cardiac output in small animals by aortic thermodilution. , 1982, The Journal of surgical research.

[12]  E. Evonuk,et al.  Cardiac output measured by thermal dilution of room temperature injectate. , 1961, Journal of applied physiology.