Protective effects of a thromboxane synthetase inhibitor and continuous arteriovenous hemofiltration in rat endotoxic shock

We determined the efficacy of continuous arteriovenous hemofiltration (CAVH) and a thromboxane synthetase inhibitor (TSI) on survival and their effect on TXA₂, PGI₂, 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 TXA₂ production, the salutary effects of CAVH appear to be from removal of an undetermined TXA₂ dependent mediator. TNFα and IL-1β concentrations do not appear to influence survival times in this model.