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Hemodynamic effects of monophosphoryl lipid A compared to endotoxin
M E Astiz1, E C Rackow, Y B Kim
1Department of Medicine, University of Health Sciences, Chicago Medical School, Illinois 60064.
Abstract:
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.
Insights
Salmonella minnesota monophosphoryl lipid A (MPL) did not cause significant hemodynamic changes in rats, unlike Salmonella minnesota lipopolysaccharide (LPS). This suggests MPL is a safer alternative to LPS for research, with limited toxicity.
Area of Science:
- Immunology
- Pharmacology
- Physiology
Background:
- Lipopolysaccharide (LPS) from Gram-negative bacteria, like Salmonella minnesota, is a potent endotoxin known to induce significant hemodynamic alterations.
- Monophosphoryl lipid A (MPL) is a detoxified derivative of LPS, recognized for its reduced toxicity while retaining some immunomodulatory properties.
Purpose of the Study:
- To compare the acute hemodynamic effects of Salmonella minnesota monophosphoryl lipid A (MPL) with Salmonella minnesota lipopolysaccharide (LPS) in a rat model.
- To evaluate the potential of MPL as a safer alternative to LPS by assessing its impact on cardiovascular parameters and capillary permeability.
Main Methods:
- Ten rats were intravenously administered either MPL or LPS at a dose of 0.25 mg/100 g.
- Mean arterial pressure (MAP), cardiac output (CO) via thermodilution, and colloid osmotic pressure (COP) were measured at baseline, 30 minutes, and 60 minutes post-administration.
Main Results:
- LPS administration led to significant decreases in CO (P < .01), MAP (P < .05), and COP (P < .05) at 30 and 60 minutes.
- MPL administration did not result in any significant changes in CO, MAP, or COP at either time point.
- These findings indicate that MPL does not induce the hemodynamic derangements or increased capillary permeability associated with LPS.
Conclusions:
- Intravenous administration of Salmonella minnesota MPL does not cause the adverse hemodynamic effects observed with LPS.
- MPL represents a safer lipid A derivative with limited toxicity compared to endotoxin.
- These results support the use of MPL in research settings where the toxic effects of LPS are undesirable.