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, TNF alpha, and IL-1beta 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). TNF alpha 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-1beta was detected earlier in Groups C,D when compared to Groups A,B (P < 0.02). TNF alpha and IL-1beta 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. TNF alpha and IL-1beta concentrations do not appear to influence survival times in this model.
Heidemann
S M
SM
Department of Pediatrics, Children's Hospital of MI, Wayne State University School of Medicine, Detroit 48201, USA.
Sarnaik
A P
AP
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003131:Combined Modality Therapy; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D011464:Epoprostenol / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006440:Hemofiltration; D007093:Imidazoles / Q000494:pharmacology; D018836:Inflammation Mediators / Q000097:blood; D007375:Interleukin-1 / Q000097:blood; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012772:Shock, Septic / Q000188:drug therapy* / Q000503:physiopathology / Q000628:therapy*; D013928:Thromboxane A2 / Q000097:blood; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D004791:Enzyme Inhibitors; D007093:Imidazoles; D018836:Inflammation Mediators; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; C039242:dazmegrel; D013928:Thromboxane A2; D011464:Epoprostenol; D013930:Thromboxane-A Synthase