LAZAROID PRETREATMENT PRESERVES GAS-EXCHANGE IN ENDOTOXIN-TREATED DOGS

Purpose: The lazaroids are a new class of potent free-radical scavenge rs. We tested whether U-74389G, a lazaroid, could attenuate some of th e adverse cardiopulmonary effects of sepsis. Methods: Dogs were random ized to receive either 10 mg/kg U-74389G (n = 10), or a saline control (n = 11). After baseline measurements of hemodynamics and gas exchang e, they were then randomized to receive either 0.2 mg/kg endotoxin or a saline infusion. Measurements of hemodynamics and gas exchange were repeated. The study was concluded 70 minutes after endotoxin infusion and the lungs were then removed for histologic evaluation. Results: In endotoxin-treated control animals. PO2 decreased (278 +/- 123 mm Hg t o 67 +/- 13 mm Hg, P < .05) and intrapulmonary shunt increased (12.9% +/- 1.1% to 28.2% +/- 11.4%. P < .05) after endotoxin. Pretreatment wi th U-74389G attenuated the decrease in PO2 (476 +/- 61 mm Hg to 226 +/ - 143) and the increase in intrapulmonary shunt (12.6% +/- 6.1% to 14. 3% +/- 6.8%) observed after endotoxin. The extent of lung injury and s ystemic hemodynamics were similar between control or U-74389G-treated dogs. Conclusions: A free-radical-scavenger can attenuate the gas exch ange defect commonly associated with endotoxin but it does not improve the derangement of systemic hemodynamics. Copyright (C) 1994 by W.B. Saunders Company