Efficiency of tazobactam/piperacillin in lethal peritonitis is
enhanced after preconditioning of rats with O3/O2-pneumoperitoneum.
Institute of Anatomy and Cell Biology,
Philipps-University of Marburg, Marburg 35033, Germany.
Insufflation of ozonized oxygen into the peritoneum
(O3/O2-pneumoperitoneum [O3/O2-PP]) of rats reduced the lethality of
peritonitis. We evaluated the prophylactic effect of O3/O2-PP combined
with tazobactam/piperacillin (TZP) in polymicrobial lethal peritonitis.
Wistar rats were conditioned by daily repeated insufflation of ozone for
5 days, and hematologic parameters were determined. Sepsis was induced
by i.p. injection of cecal material derived from donor rats.
Simultaneously, TZP was applied at a single dosage of 65 mg/kg or at two
dosage schedules of 65 mg/kg each at an interval of 1 h. The
conditioning effect of O3/O2-PP on the number of blood cells was
measured before inoculation of bacteria. The mRNA levels of
proinflammatory cytokine IL-lbeta and TNF-alpha were determined at 4 h
post infection in spleen and liver by semiquantitative in situ
hybridization analysis. Preconditioning of rats by O3/O2-PP enhanced the
number of blood leukocytes and granulocytes and increased the survival
rate of septic rats up to 33%. The combination of O3/O2-PP and TZP
further enhanced the survival rate up to 93%. This effect was
accompanied by a reduced amount of IL-1beta and TNF-alpha mRNA in spleen
and liver. In contrast, in non-infected animals the combination of
O3/O2-PP and TZP enhanced IL-1beta and TNF-alpha mRNA in the spleen and
IL-1beta mRNA in liver when compared with TZP- and sham-treated
controls. The preconditioning effect of O3/O2-PP seems to support the
biological effectiveness of TZP by altering the immune status before and
during the onset of sepsis. The combined therapy could be a simple,
preoperative intervention for abdominal surgery to reduce postoperative
morbidity and mortality.
PMID: 16369182 [PubMed - indexed for MEDLINE]