A primate model for prolonged endotoxin shock. Blood-vascular reactions and effects of glucocorticoid treatment.

A primate model was developed to study sequential blood-vascular responses, primarily of the lung and liver, and hematologic changes during prolonged endotoxemia with or without glucocorticoid treatment. In this model, pairs of animals, one with intermittent glucocorticoid regimen, were continuously infused with endotoxin throughout the experimental period. The duration of the experiment and the onset of progressive shock could be adjusted by changing the rate of endotoxin infusion. Endotoxemia at a rate of 10 mg. per kg. per hour resulted in progressive shick which was significantly delayed with glucocorticoid treatment. Endotoxin-induced hematologic alterations included early leukopenia and gradual development of disseminated intravascular coagulation. Morphologic studies revealed margination of neutrophils and mononuclear cells in the microcirculation of lung and liver. These changes were associated with sustained phagocytosis of endotoxin by the sequestered leukocytes and Kupffer cells, degranulation of the hepatic sinusoids and spaces of Disse contained extensive fibrinous deposits which in advanced stages of shock were accompanied by midzonal and centrilobular necrosis. Pulmonary lesions included margination, degranulation and fragmentation of leukocytes, early appearance of fibrin in hepatic sinusoids, and rapid development of disseminated intravascular coagulation, endothelial damage and associated lesions of lung and liver. The results indicate that events relating to sustained phagocytosis of endotoxin by the marginating leukocytes initiate a state of intravascular inflammation with disseminated intravascular coagulation and play a vasic role in the pathogenesis of pulmonary and hepatic lesions during prolonged endotoxemia leading to shock. The findings also suggest that glucocorticoid treatment attenuates endotoxin-induced blood-vascular reactions thereby providing an early protection against the development of shock and structural damage to the lung and liver.