EFFECTS OF RECONSTITUTED HIGH-DENSITY-LIPOPROTEIN IN PERSISTENT GRAM-NEGATIVE BACTEREMIA

Reconstituted high-density lipoproteins (rHDL) have been shown to bind bacterial LPS and reduce its toxic effects. Since the effect of rHDL on LPS in vitro cannot be directly extrapolated to the in-vivo picture of Gram-negative septic shock, we have investigated the effects of rH DL in a rabbit model of Gram-negative bacteremia. Rabbits were anesthe tized, ventilated, and invasively monitored for 6 hours. Escherichia c oli (4 x 10(9) CFU/kg) were infused over 2 hours in rabbits given rHDL (75 mg/kg) before the bacterial challenge. Antibiotics were not used in this model. The bacterial infusion resulted in a bacteremia that pe rsisted until the end of the study. The sepsis-induced TNF peak was si gnificantly lowered by rHDL treatment (10 +/- 3 ng/mL in rHDL treated versus 33 +/- 5 in controls, P = 0.001). Blood pressure, although not statistically significant, tended to be higher in the rHDL group. Acid osis was significantly attenuated up to 3 hours after the beginning of the bacterial challenge (7.39 +/- 0.05 versus 7.27 +/- 0.05 in contro ls, P = 0.041). rHDL treatment produced some transient beneficial effe cts in this model of persistent Gram-negative bacteremia. Additional s tudies, investigating the effects of rHDL in combination with antibiot ics, are warranted.