M. Matejovic et al., Effects of the combined thromboxane receptor antagonist and synthase inhibitor DTTX-30 on intestinal O-2-exchange and energy metabolism during hyperdynamic porcine endotoxemia, SHOCK, 13(4), 2000, pp. 307-313
Sepsis may lead to de rang ed thromboxane-prostacyclin ratio with consecuti
ve organ dysfunction. Because of the suggested role of the gut in the patho
genesis of septic shock: and multiple organ failure, we investigated the ef
fects of the novel dual thromboxane synthase inhibitor and receptor antagon
ist DTTX-30 (TRASI) on intestinal tissue perfusion, O-2, kinetics, and ener
gy metabolism over 24 h of hyperdynamic, normotensive porcine endotoxemia.
Before, 12, 18, and 24 h after starting continuous i.v. endotoxin (LPS), we
measured portal venous (PV) blood flow, intestinal oxygen extraction (iO(2
)ER), intracapillary hemoglobin O-2, saturation (HbO(2),%) of the ileal wal
l, intramucosal ileal PCO2,, PV lactate-pyruvate (L-P) ratio, and plasma le
vels of thromboxane and prostacyclin. Treatment with TRASI (0.12 mg/kg i.v.
bolus injection followed by an infusion of 0.29 mg/kg/h) initiated after 1
2 h of LPS infusion markedly reduced the plasma thromboxane levels and atte
nuated the LPS-induced fall in systemic vascular resistance, resulting in h
emodynamic stabilization. TRASI did not influence the LPS-induced increase
in PV blood flow nor intracapillary HbO(2)%, thus reflecting unchanged micr
ocirculatory O-2, availability and decreased iO(2)ER, possibly because of r
educed O-2, requirements. Nevertheless, TRASI prevented the LPS-induced inc
rease in the PV L-P ratio, attenuated the progression of the ileal mucosal-
arterial PCO2, gap, and tended to attenuate the gradual fall of PV pH. Henc
e, compounds like TRASI may beneficially influence LPS-related derangements
of gut energy metabolism.