Pathophysiologic responses of the subhuman primate in experimental septic shock

The grave clinical aspects of septic shock have stimulated the search for an experimental animal model which more closely relates to human pathophysiology. This study of the cardiovascular-pulmonary-morphologic responses of the baboon to slow infusions of live Escherichia coli organisms was designed to approximate more closely the human clinical entity. Anesthetized young adult baboons received 3-hour intravenous infusions of organisms at an average dosage of 8 times 10-9 organisms per kg. body weight. Responses of animals were followed during a period of 6 hours in the anesthetized state. There was progressive systemic hypotension and steadily decreasing cardiac output. Total peripheral resistance was uniformly depressed during the infusion, but was variable during the post-infusion survival period. Increases in heart rate, alveolar-arterial oxygen tension gradient, and oxygen uptake were uniformly present. These alterations bear close resemblance to those seen in other subhuman primates administered short term doses of live organisms. There were extensive morphologic changes in pulmonary, cardiac, and renal beds. Glomeruli contained multiple fibrin thrombi and disrupted platelets, and the glomerular capillary endothelium was focally edematous and disrupted. The myocardium exhibited capillary endothelial edema and fluid accumulation in interfiber and intrafiber spaces. There were sequestration, degranulation, and fragmentation of polymorphonuclear leukocytes and platelets, and characteristic endothelial lesions within the pulmonary vascular bed. Findings demonstrate both cardiovascular-pulmonary dysfunction and renal, cardiac, and pulmonary morphologic lesions. The baboon shock model appears to be well suited for studies of experimental septic shock and bears close resemblance to the human clinical entity.