title: Inhibition of thromboxane synthetase accentuates hemodynamic instability and burn edema in the anesthetized sheep model.
abstract: Thromboxane A2 production is increased early after burn. We studied the effect of inhibiting thromboxane synthetase, using dazmegrel, on postburn hemodynamic stability and edema formation, the latter monitored by burn tissue lymph flow. Dazmegrel (3.4 mg/kg) was given to six anesthetized sheep, and a 40% of total-body-surface third-degree burn was produced. Lactated Ringer's solution was infused at a rate to restore filling pressures during a 12-hour study period. Data were compared to burn alone (n = 8), anesthesia alone (n = 6), and dazmegrel alone (n = 5) groups. The latter two groups showed no physiologic changes. Dazmegrel pretreatment prevented increased thromboxane A2, measured as thromboxane B2, but resulted in a significant increase in plasma prostacyclin, measured as 6-keto-PGF1 alpha. In addition, a marked vasodilatation and decrease in systemic vascular resistance were noted, as well as a 30% increase in fluid requirements and an increase in lymph flow compared with burn alone. The increase in prostacyclin more than likely accentuated the burn-induced permeability change. Of interest was that oxygen consumption was better maintained with dazmegrel postburn, even with the relative hypovolemia, indicating that postburn vasoconstriction impairs adequate O2 delivery to tissues and that thromboxane synthetase inhibition attenuates this process.
authors.affiliation: Longwood Area Trauma Center Brigham and Women's, Beth Israel.
authors.forename: C
authors.initials: C
authors.lastname: LaLonde
authors.forename: R H
authors.initials: RH
authors.lastname: Demling
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000032:analysis; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001810:Blood Volume / Q000187:drug effects; D002056:Burns / Q000150:complications*; D002302:Cardiac Output / Q000187:drug effects; D004195:Disease Models, Animal; D004487:Edema / Q000209:etiology*; D006439:Hemodynamics / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology*; D008196:Lymph / Q000032:analysis / Q000502:physiology; D010101:Oxygen Consumption / Q000187:drug effects; D012756:Sheep; D012871:Skin Diseases / Q000209:etiology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D007093:Imidazoles; C039242:dazmegrel; D015121:6-Ketoprostaglandin F1 alpha; D013930:Thromboxane-A Synthase