Abstract
We determined the efficacy of continuous arteriovenous hemofiltration (CAVH) and a thromboxane synthetase inhibitor (TSI) on survival and their effect on TXA 2, PGI 2, TNFα, and IL-1β production in rat endotoxemia. Thirty-six endotoxemic rats were randomized to one of 4 groups: (A) no TSI, sham CAVH; (B) no TSI, CAVH; (C) TSI, sham CAVH; and (D) TSI, CAVH. Either CAVH (Group B) or pretreatment with TSI (Group C) resulted in increased survival time. CAVH did not prevent the rise in TX (Group B). TNFα levels at 2 h after LPS infusion were higher in Group D compared to Group B (26.1 ± 3.7 vs 13.2 ± 4.3 ng/mL, P < 0.05) respectively. IL-1β was detected earlier in Groups C,D when compared to Groups A,B ( P < 0.02). TNFα and IL-1β were not ultrafiltered. CAVH and the inhibition of TX synthesis independently improved survival in endotoxemia, however, their beneficial effects were not additive. While TSI may improve survival by blocking TXA 2 production, the salutary effects of CAVH appear to be from removal of an undetermined TXA 2 dependent mediator. TNFα and IL-1β concentrations do not appear to influence survival times in this model.
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