Cardiovascular effect of intravenous lipid A in rabbits

The in vivo cardiovascular effect of intravenous administration of monophosphoryl lipid A (mp-lipid A) and diphosphoryl lipid A (dp-lipid A) in awake New Zealand white rabbits was investigated. Observed changes were evaluated in comparison to a control group and an endotoxin-treated group. Rabbits given lipid A showed a significant depression in cardiac index (p less than .025), mean arterial pressure (p less than .025, dp-lipid A only), arterial carbon dioxide tension (p less than .025), and total leukocyte count (p less than .05) compared to controls. Animals receiving lipid A tended to respond overall in a manner closely matching that of the endotoxin group. Dosages of lipid A given were approximately 3.5 times larger than the endotoxin dosages with respect to actual number of molecules administered (1.25-2.0 times larger by mass). These results indicate that lipid A is active in producing the cardiovascular and leukopenic effects characteristic of experimental septic shock.