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 th eir effect on TXA(2), PGI(2), TNF alpha, and IL-1 beta production in r at 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 (Gr oup C) resulted in increased survival time. CAVH did not prevent the r ise in TX (Group B). TNF alpha levels at 2 h after LPS infusion were h igher in Group D compared to Group B (26.1 +/- 3.7 vs 13.2 +/- 4.3 ng/ mL, P < 0.05) respectively. IL-1 beta was detected earlier in Groups C ,D when compared to Groups A,B (P < 0.02). TNF alpha and IL-1 beta wer e not ultrafiltered. CAVH and the inhibition of TX synthesis independe ntly improved survival in endotoxemia, however, their beneficial effec ts were not additive. While TSI may improve survival by blocking TXA, production, the salutary effects of CAVH appear to be from removal of an undetermined TXA(2) dependent mediator. TNF alpha and IL-1 beta con centrations do not appear to influence survival times in this model.