Three Clinical Presentations of E. coli Sepsis as Studied in the Baboon Model

Abstract

In order for animal models of disease to be useful they must mimic the various forms of their human counterparts. In the case of disorders of gram-negative sepsis this is made difficult because circumstances at the time of infection can alter the clinical presentation of the disease. Depending upon these circumstances, the response to Escherichia coli can range from a compensated sublethal to an uncom-pensated lethal response. The pattern and sequence of organ failure ranges from early collapse of the circulatory and hemostatic systems to acute respiratory distress to development of renal failure. The physician often is forced to treat each of these empirically while waiting for antibiotics and other appropriate measures to eliminate the cause. The problem is further complicated by the fact that the causative organisms often initiate a series of injurious reactions by the host which continue long after the original cause has been eliminated. Therefore, in order to gain a better understanding the different forms of gram-negative sepsis and their relation to each other we have studied the three different lethal clinical presentations most often seen in humans, using the baboon model of E. coli sepsis. They are: (1) the composite inflammatory-coagulopathic response including hemostatic failure and gradual cardiovascular collapse in which inflammatory and coagulant elements play equal roles, (2) the immediate capillary leak response, including rapid cardiovascular collapse, in which the inflammatory elements dominate, and (3) the delayed microvascular thrombotic response including renal failure in which coagulant elements dominate.