title: Thromboxane synthase inhibition and cardiopulmonary function during endotoxemia in sheep.
abstract: We studied the cardiopulmonary response to endotoxin (lipopolysaccharide, LPS) in sheep with and without the administration of a thromboxane synthase inhibitor, OKY-046. The animals were instrumented for crystalographic dimension analysis of the left ventricle (LV) and for measurement of LV, aortic, left atrial, and pulmonary arterial pressures and cardiac index, as well as lung lymph flow. They received 1.0 micrograms/kg of Escherichia coli LPS with (n = 8) and without (n = 8) OKY-046 (10 mg/kg bolus, then 10 micrograms.kg-1.min-1). OKY-046 prevented the increase of pulmonary arterial pressure and the decrease of cardiac index that occurred during the early phase of endotoxemia. Between 8 and 12 h after LPS, cardiac index increased from 6.8 +/- 0.7 to 8.9 +/- 0.51.min-1.m-2. Concomitantly, the end-systolic pressure-diameter relationship (ESPDR, sensitive myocardial contractility index) significantly decreased from 14.7 +/- 0.6 to 7.7 +/- 0.7. Other indexes of the LV contractility (+dP/dtmax) were also reduced. OKY-046 prevented the decreases of ESPDR and +dP/dtmax. OKY-046 also attenuated the increased lung lymph flow changes seen with LPS.
authors.affiliation: Department of Anesthesiology, University of Texas Medical Branch, Galveston 77550.
authors.forename: K
authors.initials: K
authors.lastname: Fujioka
authors.forename: K
authors.initials: K
authors.lastname: Sugi
authors.forename: T
authors.initials: T
authors.lastname: Isago
authors.forename: J T
authors.initials: JT
authors.lastname: Flynn
authors.forename: L D
authors.initials: LD
authors.lastname: Traber
authors.forename: D N
authors.initials: DN
authors.lastname: Herndon
authors.forename: D L
authors.initials: DL
authors.lastname: Traber
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D015777:Eicosanoids / Q000494:pharmacology; D004731:Endotoxins / Q000633:toxicity*; D006321:Heart / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects; D008168:Lung / Q000502:physiology*; D008196:Lymph / Q000378:metabolism; D008689:Methacrylates / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects; D012756:Sheep; D013929:Thromboxane B2 / Q000097:blood; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D015777:Eicosanoids; D004731:Endotoxins; D008689:Methacrylates; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D013930:Thromboxane-A Synthase; C034364:ozagrel