DIAPHRAGMATIC FAILURE DURING GROUP-B STREPTOCOCCAL SEPSIS IN PIGLETS - THE ROLE OF THROMBOXANE A(2)

Group B Streptococcus (GBS) causes an impairment of diaphragmatic pressure generation (Pdi) in 2-wk-old piglets, whereas 4-wk-old piglets are unaffected. In this study, we examined the effect on 4-wk-old piglets of a higher dose of GBS than previously utilized. We sought to determine whether an eicosanoid product of arachidonic acid metabolism accounted for the decrease in Pdi during GBS infusion and whether thromboxane A(2) (TxA(2)) is the putative eicosanoid mediator of decreased Pdi during GBS infusion. Measuring Pdi during phrenic nerve stimulation, we studied four groups of anesthetized spontaneously breathing 4-wk-old piglets. Group 1 (GBS) was infused with live GBS, which caused a decrease in Pdi by 1 h at 20-, 30-, 50-, and 100-Hz stimulation frequencies. Group 2 [GBS + indomethacin (Indo)] was pretreated with Indo before GBS infusion. In the GBS + Indo group, Pdi did not decrease throughout 4 h of GBS infusion. Because Indo proved to be protective of Pdi during GBS infusion, we examined the role of TxA(2), the only eicosanoid present at 1 h in the serum of GBS-infused piglets. Group 3 was infused with the TxA(2) analogue U-46619 only for 1 h. Group 4 was treated with the TxA(2)-receptor antagonist SQ-29548 before and concomitant with GBS infusion for 1 h; the SQ-29548 was then discontinued, and GBS was continued for 1 h more. In the U-46619-infused group, Pdi decreased at 1 h, and in the SQ-29548-treated group, Pdi did not decrease during GBS infusion. We conclude that 1) a higher dose of GBS given to 4-wk-old piglets causes a decrease in Pdi similar to that of 2-wk-old piglets, 2) an eicosanoid is involved in this decrease in Pdi, and 3) TxA(2) is the putative eicosanoid mediator of the decrease in Pdi during GBS infusion in piglets.