Systemic
sepsis and
multiple organ failure are frequent and often fatal complications after major surgery and
trauma. In contrast to the biphasic hemodynamic pattern characteristically seen in patients, most experimental animal models have failed to reproduce the early, hyperdynamic phase of
sepsis and
endotoxemia. We have designed a standardized model of
endotoxemia, which is elicited by continuous IV infusion of Salmonella abortus equi
endotoxin in anesthetized juvenile pigs (age 8-12 weeks). The plasma concentration of
endotoxin--as evaluated by the LAL test--is significantly elevated within less than half an hour following the start of
endotoxin administration and is accompanied by a rapid fall of the leukocyte count in peripheral blood.
High cardiac output and low systemic vascular resistance reflect a hypercirculatory state, during which left ventricular filling pressure is maintained by carefully monitored volume substitution (6%
dextran 60). In the present investigation, different doses of
endotoxin (3.8 and 11.4 micrograms/kg, respectively) were infused intravenously and investigated for their effect on respiratory, macrocirculatory, and regional blood flow alterations. The development of respiratory deterioration depended on the duration of
endotoxin administration and on the height of
endotoxin plasma levels. In all animals, a
high cardiac output was maintained throughout 3.5 hr of
endotoxemia. Regional blood flow to the myocardium and liver increased, whereas blood flow to the gastrointestinal tract and the spleen was compromised without difference between both groups. It is concluded that this porcine model should provide the potential for further insight into the early pathophysiological mechanisms involved in the development of
multiple organ failure in patients with
sepsis and
endotoxemia.