Background and objective: Since the moribund hypodynamic phase of septic shock has primarily been studied in small animal models, the objective of this study was to investigate the usefulness of infusing Salmonella typhosa endotoxin at incrementing doses to establish an ovine model of hypodynamic endotoxaemia.
Methods: In a prospective laboratory experiment, eight adult ewes were instrumented for a chronic study. Following a baseline measurement in the healthy state, a continuous endotoxin infusion was started with 10 ng kg(-1) min(-1) and was doubled every hour seven times. Haemodynamics, key variables of oxygen transport, and arterial lactate concentrations were determined every hour.
Results: In a dose-dependent manner, endotoxin infusion caused pulmonary hypertension, decreased cardiac output and mean arterial pressure, increased heart rate, and to a certain extent, systemic vascular resistance index. Following 4h of endotoxaemia, the maximum decrease in cardiac output occurred (4.8+/-0.2 vs. 7.6+/-0.3 Lmin(-1); P < 0.001). This was accompanied by tissue dysoxia, represented by decreases in oxygen delivery (797+/-20 vs. 1041+/-28 mLmin(-1)), oxygen consumption (277+/-14 vs. 396+/-15 mLmin(-1)) and oxygen extraction rate (0.35+/-0.01 vs. 0.38+/-0.01%; each P < 0.01), as well as an increase in arterial lactate concentration (1.7+/-0.1 vs. 0.7+/-0.1 mmolL(-1); P < 0.05).
Conclusions: This large animal model may be helpful to study the pathophysiology responsible for cardiovascular failure, and also new therapeutic approaches relevant to management of hypodynamic circulation in the common setting of progressed systemic inflammation.