Lazaroid pretreatment preserves gas exchange in endotoxin-treated dogs.
OBJECTIVE
The lazaroids are a new class of potent free-radical scavengers. We tested whether U-74389G, a lazaroid, could attenuate some of the adverse cardiopulmonary effects of sepsis.


METHODS
Dogs were randomized to receive either 10 mg/kg U-74389G (n = 10), or a saline control (n = 11). After baseline measurements of hemodynamics and gas exchange, 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 to 67 +/- 13 mm Hg, P < .05) and intrapulmonary shunt increased (12.9% +/- 1.1% to 28.2% +/- 11.4%, P < .05) after endotoxin. Pretreatment with 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 systemic hemodynamics were similar between control or U-74389G-treated dogs.


CONCLUSIONS
A free-radical-scavenger can attenuate the gas exchange defect commonly associated with endotoxin but it does not improve the derangement of systemic hemodynamics.
Johnson
D
D
University of Saskatchewan, Saskatoon, Canada.
Hurst
T
T
Prasad
K
K
Wilson
T
T
Saxena
A
A
Murphy
F
F
Mayers
I
I
D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001784:Blood Gas Analysis; D004285:Dogs; D004731:Endotoxins / Q000009:adverse effects* / Q000378:metabolism; D005609:Free Radicals; D006439:Hemodynamics / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D011281:Pregnatrienes / Q000378:metabolism* / Q000627:therapeutic use; D011292:Premedication; D011654:Pulmonary Edema; D011659:Pulmonary Gas Exchange / Q000187:drug effects*; D011897:Random Allocation; D012772:Shock, Septic / Q000378:metabolism; D013260:Steroids, Heterocyclic / Q000378:metabolism* / Q000627:therapeutic use; D014655:Vascular Resistance / Q000187:drug effects
D000975:Antioxidants; D004731:Endotoxins; D005609:Free Radicals; D011281:Pregnatrienes; D013260:Steroids, Heterocyclic; C074965:U 74389F