A porcine model of hyperdynamic endotoxemia: pattern of respiratory, macrocirculatory, and regional blood flow changes.
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.
Institute for Surgical Research, Ludwig-Maximilians-University Munich, Klinikum Grosshadern, Germany.
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Kreimeier
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Brueckner
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Gerspach
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Veitinger
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Messmer
D000818:Animals; D016534:Cardiac Output, High / Q000139:chemically induced*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000008:administration & dosage / Q000097:blood*; D005260:Female; D006438:Hemodilution; D006439:Hemodynamics / Q000187:drug effects*; D007262:Infusions, Intravenous; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D012039:Regional Blood Flow / Q000187:drug effects; D012119:Respiration / Q000502:physiology*; D012129:Respiratory Function Tests; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects*
D004731:Endotoxins