Therapeutic trial of reconstituted human high-density lipoprotein in a canine model of gram-negative septic shock.
In a controlled, randomized trial, the authors investigated the effects of reconstituted human high-density lipoprotein (R-HDL) on survival, endotoxemia, cytokine production and pathophysiologic and metabolic events in an animal model of gram-negative septic shock. At 0.5, 8 and 16 hr after implantation of a clot infected with Escherichia coli, canines received intravenous R-HDL (n = 13), control lipid (n = 7) or human serum albumin (HSA, n = 7) divided into three doses (0.3, 0.1 and 0.1 g/kg, respectively) at an hourly rate of 0.1 g/kg. All animals were treated with antibiotics and fluids. Animals treated with R-HDL had lower levels of circulating endotoxin and tumor necrosis factor and a smaller decrease in white blood cell counts than did animals treated with lipids and HSA (all P < .05). The survival times of lipid- and HSA-treated animals were similar (P = .3) and were significantly greater than those of R-HDL-treated animals (P = .02). During the first 6 hr after clot implantation, R-HDL-treated animals had significantly greater abnormalities in liver function test findings compared with lipid- and HSA-treated animals (all P < .05). For the first 24 hr, R-HDL-treated animals had significant increases in HDL levels; however, there were no significant relationships between these levels and the constituents of HDL (apolipoprotein AI and phosphatidylcholine) or liver function abnormalities and survival times (all r < .2, P > .3). In normal animals, administration of R-HDL (in similar doses) caused transient elevation of liver enzymes; in animals given sterile clot i.p., R-HDL caused seizures.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Critical Care Medicine, National Institutes of Health, Bethesda, Maryland.
Z M
ZM
Quezado
C
C
Natanson
S M
SM
Banks
D W
DW
Alling
C A
CA
Koev
R L
RL
Danner
R J
RJ
Elin
J M
JM
Hosseini
T S
TS
Parker
D M
DM
Levine
D000818:Animals; D001053:Apolipoproteins / Q000097:blood; D004195:Disease Models, Animal; D004285:Dogs; D004731:Endotoxins / Q000097:blood; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy*; D008077:Lipoproteins, LDL / Q000627:therapeutic use*; D008099:Liver / Q000503:physiopathology; D012772:Shock, Septic / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D001053:Apolipoproteins; D004731:Endotoxins; D008077:Lipoproteins, LDL; D014409:Tumor Necrosis Factor-alpha