A new canine model of endotoxin shock

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 ca-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-lfollowed 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). Hypovolaemia 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-, 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. IntroductionAnimal models have been widely used for the investigation of septic shock, a condition which in man still carries a mortality of up to 50% (Schumer, 1979).Many workers have performed endotoxin-based experiments, and there is a wealth of literature describing the effects of endotoxin in different species of experimental animals (Halmagyi et al., 1963;Brockman et al., 1967; Kuida etal., 1971; Balis etal., 1978;Morris et al., 1979). This subject has been comprehensively reviewed by Gilbert (1960).However, concern has recently been expressed with regard to the clinical relevance of endotoxin models (Wichterman et al., 1980) and alternatives which attempt to represent more exactly the clinical situation have been suggested. These have included 1Correspondence. the intravenous infusion of live bacteria into mongrel dogs, sheep, pigs and rhesus monkeys (Pool et al., 1977;Hinshaw et al., 1979;Fairman & Glauser, 1980;Gahos et al., 1982). Other models have involved the induction of peritonitis, for example, by implantation of a septic sponge or ...

Adrenal vein and arterial levels of catecholamines and immunoreactive metenkephalin in canine endotoxin shock and their response to naloxone

“…The alterations in plasma levels of catecholamines and ir-metenkephalin in adrenal vein and arterial blood in response to endotoxin, as well as the effects of subsequent naloxone administration, have therefore been investigated in a previously described canine model of endotoxin shock [12].…”

Respiratory gas exchange as a new aid to monitor acidosis in endotoxemic rats: relationship to metabolic fuel substrates and thermometabolic responses

“…The associated fall in pH was similarly phasic and consistent with the timing of the RER response. These observations contrast with those reported for anesthetized animals, in which acidosis was portrayed as a progressive phenomenon (Parratt and Sturgess 1974;Jacobs et al 1982;Evans et al 1984;Schaefer et al 1995;Dubin et al 2005;Andersson et al 2006;Scheiermann et al 2011;Sand et al 2015). Interestingly, there is evidence to suggest that other responses to LPS have distinct time-courses in anesthetized versus unanesthetized animals.…”

“…As much as this method is accurate, it provides data with poor temporal resolution. Additionally, the need for serial blood draws has favored experimentation under anesthesia in all species investigated: dog (Jacobs et al 1982;Evans et al 1984), sheep (Dubin et al 2005), pig (Andersson et al 2006), cat (Parratt and Sturgess 1974), rat (Schaefer et al 1995;Scheiermann et al 2011), and mouse (Sand et al 2015). These studies led to the notion that acidosis is a progressive phenomenon in endotoxic shock, but this notion must still pass scrutiny in studies with better temporal resolution.…”

Plasma levels of neuropeptide tyrosine Y (NPY) are increased in human sepsis but are unchanged during canine endotoxin shock despite raised catecholamine concentrations

“…Using dogs (Evans, Hinds & Varley, 1984) we have investigated changes in circulating and adrenal vein levels of catecholamines and immunoreactive NPY (ir-NPY) in response to severe, persistent endotoxin shock. We also measured ir-NPY levels in five patients with septic shock.…”