SYNERGISM OF ALVEOLAR ENDOTOXIN PRIMING AND INTRAVASCULAR EXOTOXIN CHALLENGE IN LUNG INJURY

Both endotoxin (lipopolysaccharides of gram-negative bacteria; LPS) an d bacterial exotoxins may induce pulmonary microcirculatory disturbanc es when infused into the lung vasculature, and synergism between these types of microbial challenge has recently been noted. We now asked wh ether a bronchoalveolar LPS load in perfused rabbit lungs alters the r esponsiveness to a subsequent intravascular challenge with Escherichia coli hemolysin (ECH). In control lungs (sham aerosolization) and lung s undergoing LPS nebulization (alveolar deposition of similar to 22 mu g), normal pulmonary artery pressure (PAP), lung weight, and ventilat ion/perfusion (V/Q) matching were observed. Intravascular ECH (0.013 h emolytic units/ml buffer fluid) increased PAP by similar to 10 mm Hg a nd lung weight by similar to 4 g within 10 min, paralleled by V/Q mism atch and a shunt Row of similar to 15%. In lungs ''primed'' for 3 h by a preceding bronchoalveolar LPS deposition, the same ECH dose provoke d a dramatic increase in PAP to 40 to 50 mm Hg, a weight gain of simil ar to 10 g, and shunt flow of 60%. Both vasoconstrictor response and V /Q mismatch were completely suppressed by preadministration and ''resc ue'' application of the thromboxane receptor antagonist BM13.505. We c onclude that a bronchoalveolar endotoxin load, though effecting no cha nges in pulmonary function by itself and showing no spillover into the vascular compartment, primes the lungs for a manifold increased vascu lar response to a subsequently infused exotoxin. Enhanced thromboxane- mediated vasoconstriction, largely redistributing perfusate flow from normally ventilated to shunt areas, is suggested as the predominant un derlying event.