RETROSPECTIVE DESCRIPTION AND EXPERIMENTAL RECONSTITUTION OF 3 DIFFERENT RESPONSES OF THE BABOON TO LETHAL ESCHERICHIA-COLI

This paper is divided into a retrospective descriptive section in whic h we report on three distinctly different and spontaneous responses of the baboon to LD(100) Eschericia coli observed over the last 6 years. This section is followed by an experimental section in which we repro duce the immediate and delayed responses based on hypothetical mechani sms. In the descriptive section, we arbitrarily divided all the non-su rvivor animals on which we had sufficient data into three groups based on duration of survival (i.e., 12 hr or less, immediate, 12 to 30 hr, intermediate, and 30 hr or more, delayed). The natural history and pa thophysiology of the 12 hr or less group matched that of capillary lea k syndrome with a rapid fall in blood pressure, rise in hematocrit, ma ssive edema, and congestion with leukocyte sequestration in both lung and liver, with only limited adrenal cortical hemorrhage. The 12 to 30 hr group matched the natural history of a consumptive hemorrhagic dia theses with a biophasic blood pressure response, limited change in hem atocrit, a severe consumptive coagulopathy, severe adrenal cortical he morrhage, and a moderate renal cortical tubular necrosis, but limited renal cortical thrombosis. The greater than 30 hr group matched the na tural history of a microvascular thrombotic (hemolytic uremic) syndrom e with a stable blood pressure, a fall in hematocrit associated with a massive renal cortical thrombosis with a severe medullary, and cortic al tubular necrosis. We did not analyze these groups further (i.e., ty pe of intervention etc.) once we found that time of survival correlate d with a unique clinical syndrome, because based on these observations , we hypothesized that we could reproduce the immediate capillary leak and pulmonary failure, and the delayed microvascular thrombosis and r enal failure syndromes experimentally. We reproduced the immediate (<1 2 hr) and delayed (>30 hr) responses by infusion of either tumor necro sis factor or C4b binding protein with sublethal E. coli. This provide s models of the immediate and delayed as well as the intermediate resp onses to E. coli for study of mechanism and the efficacy of therapeuti c interventions. (C) 1994 Wiley-Liss, Inc.