Hemodynamic effects of monophosphoryl lipid A compared to endotoxin.
The acute hemodynamic effects of Salmonella minnesota monophosphoryl lipid A (MPL) were compared with Salmonella minnesota lipopolysaccharide (LPS) in rats. Ten animals were randomized to receive either 0.25 mg MPL/100 g or 0.25 mg LPS/100 g intravenously. Arterial pressure (MAP), thermodilution cardiac output (CO), and colloid osmotic pressure (COP) were measured prior to and 30 and 60 min after MPL or LPS administration. In LPS-treated animals, CO decreased from 356 +/- 23 to 229 +/- 24 ml/kg/min at 30 min (P less than .01). MAP decreased from 115 +/- 7 to 89 +/- 2 mm Hg (P less than .05), and COP decreased from 18.4 +/- 0.6 to 15.4 +/- 0.8 mm Hg (P less than .05) at 60 min. In MPL-treated animals, no significant changes were observed in CO, MAP, and COP at 30 and 60 min. Intravenous infusion of MPL does not produce the hemodynamic derangements or increases in capillary permeability observed with endotoxin. These observations are consistent with previous reports demonstrating the limited toxicity of this lipid A derivative.
Astiz
M E
ME
Department of Medicine, University of Health Sciences, Chicago Medical School, Illinois 60064.
Rackow
E C
EC
Kim
Y B
YB
Weil
M H
MH
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000187:drug effects*; D004731:Endotoxins / Q000633:toxicity*; D008050:Lipid A / Q000378:metabolism / Q000633:toxicity*; D010766:Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains; D012475:Salmonella; D013997:Time Factors
D004731:Endotoxins; D008050:Lipid A