Clinical and Experimental Study on Septic Adult Respiratory Distress Syndrome (ARDS) : on the role of granulocytes

Abstract

The role of granulocytes in ARDS-developing in the sepsis occurred by gram-negative rods and in the endotoxin induced pulmonary edema has been investigated. 1. The septic ARDS in clinical cases indentified were found in 30 cases of sepsis occurred gramnegative rods among 31 cases with all septic patients. Furthermore, 18 cases out of all patients were measured their serum endotoxin, and all cases of them showed positive sign in Limulus test. From these results, it suggests that endotoxin has closely relates to the outbreak of septic ARDS. Therefore, endotoxin was used in this experimental study. 2. The morphologic findigs of pulumonary edema were observed at 48 hours after the endotoxin injection to the experimental animals. 3. Peripheral polymorphonuclear leukocyte (PMN) count rapidly and immediately decreased after the endotoxin injection. These PMNs were strongly adhered to endothelial cells in pulmonary vessels. Their lysosomal enzymes were released out, shown by an electron-microscopic fiidings of PMNs. The serum level of β-glucronidase were rapidly increased. And the edematous changes in lung tissue were observed by the injection of free-β-glucronidase. From the results of the incubation of human PMNs and endotoxin in in vitro system, it is found that the superoxide production of PMNs was increased. Moreover, by the addition of human serum, the production of it increased more. The edematous changes of lung tissue in endotoxin rats suppressed by intraperitoneally contiuous treatment of superoxide dismutase. 4. The edematous change in endotoxin lung was remakably suppressed in the leukopenic animals which were made by pre-treatment with nitrogen mustard. In retrospective observation of 107 patients with sepsis occurred by gram-negative rods, the incidence of ARDS-developing was 28.8% in 93 patients whose leukocyte count was more than 3, 000/mm^3. However, no cases of ARDS was seen in 14 patients whose peripheral leukocyte count was less than 3, 000/mm^3. 5. From above results, it might be suggested that the PMN action was strongly related to the outbreak of ARDS in the cases with sepsis occurred by gramnegative rods. The mechanisms might be explained as follows. PMNs are activated by endotxin. They are more activated by addition of serum. Activated PMNs were adhered to capillary endothelium in lung tissue, and they were destroyed on the surface of endothelium. The β-glucronidase and O_2- are released from PMNs. Such releasing products injered the endothelial cell of pulmonary vessels. Therefore. The permeability of capillary wall is increased, and them pulmonary edema occurres. These experimental results on the changes of PMNs also suggest the mechanism of the outbreak of clinical septic ARDS, too. The PMNs actions that were observed in this experimental study might make an important role in the clinical developing of the septic ARDS.