A porcine model of early adult respiratory distress syndrome induced by endotoxaemia.
To study the pathophysiology of early adult respiratory distress syndrome (ARDS) induced by sepsis, spontaneously breathing pigs under ketamine anaesthesia were investigated. Twenty animals were infused i.v. with E. coli endotoxin (10 micrograms . h-1 . kg-1) over 6 h, and ten control animals received physiological saline. In the controls, cardiac output (Qt) and O2 delivery decreased slightly. There were no changes in pulmonary gas exchange, pulmonary haemodynamics or extravascular lung water (EVLW). The polymorphonuclear (PMN) leucocyte count gradually increased, while the platelet count decreased slightly. Endotoxin infusion caused profound deterioration of pulmonary gas exchange, a marked rise in pulmonary vascular resistance (PVR) and a moderate increase in EVLW. The pulmonary dysfunction was not attributable to the pulmonary oedema per se, whereas a "dry" ventilation/perfusion inequality played an important role. The "responders" (peak venous admixture greater than 20%; n = 14) were characterized by higher Qt and lower PVR than the "non-responders". Qt declined progressively, especially in non-survivors. O2 delivery decreased considerably. Metabolic acidosis probably indicated oxygen deficit. Eleven of 20 animals died during the observation period. Mortality was related more to the imbalance between O2 delivery and oxygen demand than to the deterioration in pulmonary gas exchange. The PMN count decreased markedly while the gradual decline in platelet count was similar to that in the controls. Lung microscopy revealed PMN accumulation in the microvasculature, moderate interstitial oedema and microvascular blood stasis. Our porcine model, which closely mimics early ARDS in man, will be useful in further studies of the pathophysiological pathways and the treatment of this syndrome.
D000136:Acid-Base Equilibrium; D000818:Animals; D001784:Blood Gas Analysis; D001834:Body Water / Q000378:metabolism; D004195:Disease Models, Animal; D004731:Endotoxins / Q000633:toxicity*; D004926:Escherichia coli; D005260:Female; D006400:Hematocrit; D006439:Hemodynamics; D006454:Hemoglobins / Q000378:metabolism; D007958:Leukocyte Count; D008297:Male; D009929:Organ Size; D010101:Oxygen Consumption; D010976:Platelet Count; D011652:Pulmonary Circulation; D012128:Respiratory Distress Syndrome / Q000097:blood / Q000139:chemically induced* / Q000503:physiopathology; D013552:Swine
D004731:Endotoxins; D006454:Hemoglobins