Effects of the combined thromboxane receptor antagonist and synthase inhibitor DTTX-30 on intestinal O-2-exchange and energy metabolism during hyperdynamic porcine endotoxemia

Citation
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
Citations number
41
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
SHOCK
ISSN journal
1073-2322 → ACNP
Volume
13
Issue
4
Year of publication
2000
Pages
307 - 313
Database
ISI
SICI code
1073-2322(200004)13:4<307:EOTCTR>2.0.ZU;2-W
Abstract
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.