R. Lundblad et Ke. Giercksky, SYNERGISTIC EFFECT OF E5, IMIPENEM, AND VOLUME SUPPORT DURING FULMINANT INTRAABDOMINAL SEPSIS IN RATS, The Journal of infectious diseases, 172(1), 1995, pp. 152-160
The protective effect of volume support, imipenem, and the anti-endoto
xin antibody E5 given as mono- or combination therapy was studied in f
ulminant intraabdominal sepsis in rats. Mortality, blood levels of bac
teria, endotoxin, tumor necrosis factor (TNF), and lactate, and packed
cell volume were measured. AU monotherapy regimens improved survival,
and protection decreased with delayed intervention. Volume support pr
evented dehydration and lactate accumulation but had no effect on leve
ls of bacteria, endotoxin, or TNF. Imipenem killed bacteria and releas
ed endotoxin, and lactacidosis was reduced. E5 reduced endotoxin, TNF,
and lactate but not bacteremia. The imipenem-induced increase in plas
ma endotoxin was abolished by E5. When E5 was added to a regimen of vo
lume support plus imipenem 6 h after induction, it gave an extra impro
vement of survival, but this synergism disappeared when intervention w
as delayed 4 h more. The primary effect of E5 was a reduction in plasm
a endotoxin level.