RT Journal Article
SR Electronic
T1 Therapeutic trial of reconstituted human high-density lipoprotein in a canine model of gram-negative septic shock.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 604
OP 611
VO 272
IS 2
A1 Quezado, Z M
A1 Natanson, C
A1 Banks, S M
A1 Alling, D W
A1 Koev, C A
A1 Danner, R L
A1 Elin, R J
A1 Hosseini, J M
A1 Parker, T S
A1 Levine, D M
YR 1995
UL http://jpet.aspetjournals.org/content/272/2/604.abstract
AB 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)