u-75412e and Burns

This study examined the hypothesis that burn injury inhibits the release of splanchnic PGI2, a potent endogenous vasodilator of the splanchnic vascular bed. Male Hartley Guinea Pigs (350 grams) were anesthetized, shaved and subjected to a full thickness scald burn comprising 45% of the total body surface area (or sham burn). The animals were treated with intravenous or topical lazaroid, a 21-aminosteroid U75412E. After recovery for 24 hours, the animals were anesthetized, and the superior mesenteric artery was cannulated and removed with its intact intestine (SV + SI). The SV + SI was perfused in vitro with oxygenated Krebs buffer. The venous effluent was assayed for 6-keto-PGF1 alpha, PGE2 and thromboxane B2 by enzyme immunoassay. Acute burn injury decreased SV + SI release of 6-keto-PGF1 alpha by 57% but did not alter release of PGE2 or thromboxane B2. Treatment of the animals with topical lazaroid and not intravenous lazaroid restored SV+SI 6-keto-PGF1 alpha release to control levels. These data showed that topical lazaroid therapy maintained endogenous splanchnic PGI2 release following acute burn injury. Maintaining endogenous splanchnic PGI2 release by topical lazaroid treatment may be one strategy to avoid splanchnic ischemia following acute thermal injury.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Burns; Dinoprostone; Epoprostenol; Guinea Pigs; In Vitro Techniques; Kinetics; Male; Mesenteric Arteries; Perfusion; Splanchnic Circulation; Steroids; Thromboxane B2

Thermal energy causes an immediate, irreversible injury at the burn site, followed by a delayed, reversible tissue loss in the area surrounding the burn site due to progressive ischemia. We investigated the role of lipid peroxidation in the pathogenesis of progressive ischemia in a rat burn model. The burn model consisted of a row of four 10 x 20 mm burns separated by three unburned 5 x 20 mm skin bridges (interspaces). The interspaces became ischemic and necrotic by 24 hours, producing a single wound with the merger of the burn sites. U75412E, a lipid peroxidation inhibitor, preserved vascular patency, restored blood flow, prevented a rise in tissue conjugated dienes, and maintained tissue viability in the interspaces. Four separate burn wounds healed between three viable strips of hair-bearing interspaces. The treatment was effective, when given systemically during the period between 2 hours before and 1 hour after the burn. U75412E prevented progressive burn ischemia and the expansion of tissue loss.

Topics: Animals; Blood Vessels; Burns; Ischemia; Latex; Male; Models, Anatomic; Rats; Rats, Sprague-Dawley; Regional Blood Flow; Skin; Steroids