Fibrinogen depletion and control of permeability in oleic acid lung injury

To determine if the biphasic pulmonary clearance of aerosolized 99mTc diethylene penta acetate (99mTc-DTPA) observed in oleic acid lung injury represents acute epithelial damage followed by sealing as a result of intra-alveolar fibrin deposition, we examined the effect of fibrinogen depletion. 99mTc-DTPA clearance was assessed in three groups of rabbits: Group 1, normal fibrinogen + oleic acid injury; Group 2, fibrinogen-depleted + oleic acid injury; Group 3, fibrinogen-depleted with no oleic acid injury. In Group 3 animals with no lung injury, the 99mTc-DTPA clearance rate, expressed as k, the percent decrease in thoracic radioactivity, was similar to that previously reported for healthy rabbits (k = 1.16 +/- 0.57%/min, mean +/- SD). Oleic acid administration to Groups 1 and 2 resulted in significantly faster clearance rates, with identical biphasic curves in all animals, irrespective of fibrinogen status. There were no significant differences between either the initial fast phase (k, Group 1 = 5.26 +/- 1.83%/min, Group 2 = 5.70 +/- 1.77%/min) or the subsequent slow phase (k, Group 1 = 1.67 +/- 0.63%/min, Group 2 = 1.57 +/- 0.55%/min, p greater than 0.05). On histologic examination, Groups 1 and 2 showed greater cellular interstitial infiltrate, alveolar edema, and hemorrhage than did Group 3. Fibrinogen depletion plus oleic acid injury resulted in greater alveolar cellular exudate, edema, and hemorrhage than did either oleic acid or fibrinogen depletion alone. We conclude that fibrinogen is not necessary to produce biphasic 99mTc-DTPA clearance in oleic acid lung injury.