title: Effects of thromboxane synthetase inhibition on postburn mesenteric vascular resistance and the rate of bacterial translocation in a chronic porcine model.
abstract: It is known that thromboxane (TX)B2, the metabolite of the potent vasoconstrictor TXA2, is elevated markedly in the serum of the patients immediately postburn. We had shown that extensive thermal injury causes a reduction in mesenteric blood flow that can lead to bacterial translocation from the intestine. In this study, we tested the hypothesis that the TX synthetase inhibitor, OKY-046, prevents increased mesenteric vascular resistance (MVR) and decreases the rate of translocation of bacteria seen after extensive thermal injury. Pigs in groups 1 (n = 6) and 2 (n = 6) had third degree burns of 40 per cent total body surface area under general anesthesia and were resuscitated according to the Parkland formula. Pigs in group 2 received 10 milligrams per kilogram of OKY-046 as a bolus just before the burn and 10 grams per kilogram per minute for 16 hours as a continuous infusion. Pigs in group 3 (control, n = 6) underwent general anesthesia only and received daily maintenance fluids of lactated Ringer's solution, 2 milliliters per kilogram per hour. OKY-046 prevented the significant increase in MVR seen during the first eight hours after burn. The total peripheral resistance (TPR) showed an early increase and a late decrease in the burn group, while the cardiac index (CI) and temperature (T) significantly increased after 24 hours. Administration of OKY-046 kept TPR, Cl, and T remarkably stable. OKY-046 reduced the rate of translocation of bacteria seen in the burn group from 67 to 17 per cent. Our results show that the blockade of thromboxane synthesis by OKY-046 prevented the early mesenteric vasoconstriction and the late hyperdynamic response seen after thermal injury and was useful in reducing the incidence of postburn translocation of bacteria.
authors.affiliation: University of Texas Medical Branch, Galveston.
authors.forename: R
authors.initials: R
authors.lastname: Tokyay
authors.forename: H M
authors.initials: HM
authors.lastname: Loick
authors.forename: D L
authors.initials: DL
authors.lastname: Traber
authors.forename: J P
authors.initials: JP
authors.lastname: Heggers
authors.forename: D N
authors.initials: DN
authors.lastname: Herndon
mesh_terms: D000818:Animals; D001419:Bacteria / Q000302:isolation & purification*; D002056:Burns / Q000382:microbiology* / Q000503:physiopathology*; D005260:Female; D006439:Hemodynamics; D007422:Intestines / Q000382:microbiology; D008689:Methacrylates / Q000494:pharmacology*; D013152:Splanchnic Circulation / Q000187:drug effects*; D013552:Swine; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects*
chemical_list: D008689:Methacrylates; D013930:Thromboxane-A Synthase; C034364:ozagrel