Recombinant amino terminal fragment of bactericidal/permeability-increasing protein prevents hemodynamic responses to endotoxin.
We sought to determine if a recombinant amino terminal fragment of bactericidal/permeability increasing protein (rBPI23) alters the hemodynamic responses to endotoxin. Experiments were performed on Sprague Dawley rats anesthetized with Ketamine and xylazine. In rats challenged with a 30 min infusion of 0.25 mg/kg lipopolysaccharide (LPS; Escherichia coli 0111:B4), there were early (30-90 min), significant increases in cardiac index, heart rate, and stroke volume, accompanied by significant decreases in blood pressure and total peripheral resistance. For the remainder of the 210 min observation period, cardiac index, and stroke volume progressively declined to levels significantly below those of control rats receiving only vehicles. At the same time, blood pressure and total peripheral resistance steadily increased above the vehicle control group. Infusion of 3 mg/kg of rBPI23 abolished these LPS-induced hemodynamic responses. A dose of 1.0 mg/kg of rBPI23 was associated with a modest, significant inhibition of changes evoked by LPS, whereas 0.3 mg/kg was without significant effect. Thaumatin, a control cationic protein with molecular weight and isoelectric point similar to those of rBPI23, failed to alter any responses to LPS. These results indicate that rBPI23 produces a dose-dependent inhibition of hemodynamic changes, associated with endotoxemia, and provides further support for the potential utility of rBPI23 as a therapeutic agent in the treatment of gram-negative sepsis and infection.
Ammons
W S
WS
Department of Pharmacology and Toxicology, XOMA Corporation, Berkeley, California 94710.
Kung
A H
AH
D000818:Animals; D023181:Antimicrobial Cationic Peptides; D001794:Blood Pressure / Q000187:drug effects; D001798:Blood Proteins / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D008565:Membrane Proteins; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013318:Stroke Volume / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D010446:Peptide Fragments; C021623:bactericidal permeability increasing protein