Tissue and plasma putrescine levels in non-survivors of sepsis in a fluid-resuscitated rat model of faecal peritonitis
Intensive Care Medicine Experimentalvolume 3, Article number: A616 (2015)
The polyamine, putrescine, was first isolated from putrefying meat but is thought to play an important role in cell growth and differentiation (). It also generates succinate via GABA and can thus serve as an energy source to the small intestine (). Elevated plasma putrescine levels have been reported in an endotoxic rodent model (). We have previously characterized a 72 h fluid-resuscitated rat model of faecal peritonitis where prognostication can be accurately made as early as 6 h post-insult ().
Using this long-term sepsis model, to assess differences in liver and plasma levels of putrescine in predicted survivors and non-survivors.
Awake, instrumented yet fully mobile male Wistar rats (325 ± 15 g) received an i.p. injection of 4µl/g faecal slurry. Fluid resuscitation (50:50 mix of 5% glucose/Hartmann's; 10 ml/kg/h) was commenced at 2 h. At 6 h, an echo-measured heart rate cut-off of 460 bpm was used to classify animals into predicted survivors or non-survivors. Animals were sacrificed at 6 h, 24 h or 72 h for liver and blood sampling. A group of control animals were treated identically but without injection of faecal slurry. Putrescine levels were measured using mass spectrometry. Results were analysed using two-way ANOVA and post-hoc testing and considered statistically significant when p < 0.05.
In this model septic animals had a mortality rate of 56% with death occurring between 18-36 h. At 6 h septic animals displayed only mild clinical features of illness. However, even as early as 6 h, significant differences were noted in putrescine levels in liver and plasma from non-surviving septic animals.
An association was seen between eventual non-survival and elevated putrescine levels in both liver and plasma at both 6 h and 24 h. The significance of this finding warrants further investigation.
ESICM Basic Science Award, Intensive Care Foundation (UK), NIHR
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