A pathophysiological and histological study of experimentally induced lung damage in the mouse and the rabbit
The adult respiratory distress syndrome (ARDS) is a life threatening complication with a high mortality rate which occurs in patients in a variety of situations. The diverse aetiologies of the syndrome have led to difficulties in defining and diagnosing those patients suffering from ARDS.This thesis describes the induction of pulmonary damage in two animal species, using a number of stimuli in an attempt to mimic the histological damage seen at autopsy in patients who have died of the adult respiratory distress syndrome. The intravenous administration of oleic acid in both mouse and rabbit induced fat embolism and lung pathology similar to that seen in some ARDS patients. In the rabbit these histological changes have been correlated with physiological measurements made during the course of the damage. In the anaesthetised, spontaneously breathing rabbit gram-negative scepticaemia, a major precursor of ARDS in humans, was induced by the intravenous administration of live E.Coli bateria. Physiological measurements relevant to pulmonary gas exchange efficiency were made during the course of the infusion of bacteria and for several hours after. The lung damage induced by gram-negative sepsis in the rabbit has been compared to that induced by oleic acid emoblism, E. Coli endotoxin and phorbol myristate acetate. The role of the polymorphonuclear leucocyte in the pathogenesis of lung damage induced by several of the stimuli used in these experiments has been studied in both the mouse and the rabbit models described in this thesis.