Neutrophil accumulation and structural changes in nonpulmonary organs after acute lung injury induced by phorbol...

Multiple nonpulmonary organ failure contributes significantly to the high mortality rate associated with the adult respiratory distress syndrome (ARDS). However, little is known about specific structural and/or functional alterations that occur in nonpulmonary organs in this syndrome. Therefore, the present study was designed to test the hypothesis that inflammatory cell infiltration and structural changes occur both in the lungs and in nonpulmonary organs in ARDS. To test this hypothesis, neutrophil accumulation and structural alterations were evaluated in nonpulmonary organs from dogs with acute lung injury produced by intravenous phorbol myristate acetate (PMA) (30 micrograms/kg; n = 5). As expected, morphologic changes were present in the lungs of the PMA-treated animals and included a diffuse neutrophilic pneumonitis with interstitial, vascular, and alveolar components. PMA-treated dogs had significant increases in neutrophils (expressed as PMN/mm2 tissue section area) compared with those in control animals in the following organs: heart, 14 +/- 3 versus 4 +/- 1; brain, 2.5 +/- 0.3 versus 0.7 +/- 0.3; duodenum, 34 +/- 7 versus 10 +/- 2; liver, 397 +/- 16 versus 103 +/- 12 (p less than 0.025, all comparisons). In addition, severe necrosis and inflammation of vessels, sinusoidal thrombosis, and hepatic necrosis were noted in the liver. Like the changes noted in the lung, hepatic lesions appeared to be vascular in origin and were consistent with lesions produced by the intravascular activation of neutrophils. No microscopic lesions were detected in the brain, kidney, duodenum, and heart. Taken together, the finding of concurrent lung injury, liver injury, and nonpulmonary organ neutrophil accumulation suggests the possibility of a common pathway of injury in this model of ARDS.