A new canine model of endotoxin shock

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Abstract
1 A new canine model of endotoxin shock has been developed in which spontaneous recovery of cardiovascular function is largely prevented, the haemodynamic effects of anaesthesia are minimized and intravascular volume replacement is given. 2 This model has been evaluated using two groups of five adult mongrel dogs anaesthetized with α-chloralose and breathing spontaneously. Animals in one group were anaesthetized, instrumented and given Escherichia coli (E. coli) endotoxin intravenously, whilst those in the control group were subjected only to anaesthesia and instrumentation. 3 E. coli endotoxin was given to dogs in the shock group as a bolus dose of 5 mg kg−1 followed by a continuous infusion at 2 mg kg−1 h−1. This produced immediate, severe, cardiovascular depression, with precipitous falls in mean arterial pressure (MAP), cardiac index (CI), stroke index (SI) and left ventricular (LV) dp/dt max. There were associated increases in systemic and pulmonary vascular resistances. Arterio-venous oxygen content difference (C(a-v)O2) increased after induction of shock, and animals developed a progressive metabolic acidosis. Increasing haemoconcentration occurred, as evidenced by a rising haematocrit (PCV). Hypovolemia was reflected by a concurrent fall in pulmonary capillary wedge pressure (PCWP). 4 One hour after induction of shock, intravascular volume replacement was given in the form of a colloidal gelatin solution, as a bolus dose of 10 ml kg−1, followed by a continuous infusion at 10 ml kg−1 h−1. Volume replacement reversed haemoconcentration, restored PCWP and produced some haemodynamic improvement, although in general, severe cardiovascular depression persisted throughout a three hour observation period. 5 This severe endotoxin shock model has proved to be stable, reproducible and economical. It provides a useful preliminary test for new methods of treatment in hypodynamic endotoxin shock, as well as allowing investigation of acute metabolic and physiological changes.