Effects of reconstituted high-density lipoprotein in persistent gram-negative bacteremia.
Reconstituted high-density lipoproteins (rHDL) have been shown 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 rHDL in a rabbit model of Gram-negative bacteremia. Rabbits were anesthetized, ventilated, and invasively monitored for 6 hours. Escherichia coli (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 persisted until the end of the study. The sepsis-induced TNF peak was significantly 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. Acidosis was significantly attenuated up to 3 hours after the beginning of the bacterial challenge (7.39 +/- 0.05 versus 7.27 +/- 0.05 in controls, P = 0.041). rHDL treatment produced some transient beneficial effects in this model of persistent Gram-negative bacteremia. Additional studies, investigating the effects of rHDL in combination with antibiotics, are warranted.
Casas
A T
AT
ZLB Central Laboratory, Blood Transfusion Service, Swiss Red Cross, Bern, Switzerland.
Hubsch
A P
AP
Doran
J E
JE
D000818:Animals; D016470:Bacteremia / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000378:metabolism; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D011817:Rabbits; D011994:Recombinant Proteins; D012772:Shock, Septic / Q000188:drug therapy / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D008075:Lipoproteins, HDL; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha