'Preconditioning' with low dose lipopolysaccharide aggravates the organ injury / dysfunction caused by hemorrhagic shock in rats.

Abstract

METHODS:

Male rats were 'pretreated' with phosphate-buffered saline (PBS; i.p.) or LPS (1 mg/kg; i.p.) 24 h prior to HS. Mean arterial pressure (MAP) was maintained at 30 ± 2 mmHg for 90 min or until 25% of the shed blood had to be re-injected to sustain MAP. This was followed by resuscitation with the remaining shed blood. Four hours after resuscitation, parameters of organ dysfunction and systemic inflammation were assessed.

RESULTS:

HS resulted in renal dysfunction, and liver and muscular injury. At a first glance, LPS preconditioning attenuated organ dysfunction. However, we discovered that HS-rats that had been preconditioned with LPS (a) were not able to sustain a MAP at 30 mmHg for more than 50 min and (b) the volume of blood withdrawn in these animals was significantly less than in the PBS-control group. This effect was associated with an enhanced formation of the nitric oxide (NO) derived from inducible NO synthase (iNOS). Thus, a further control group in which all animals were resuscitated after 50 min of hemorrhage was performed. Then, LPS preconditioning aggravated both circulatory failure and organ dysfunction. Most notably, HS-rats pretreated with LPS exhibited a dramatic increase in NF-κB activation and pro-inflammatory cytokines.

CONCLUSION:

In conclusion, LPS preconditioning predisposed animals to an earlier vascular decompensation, which may be mediated by an excess of NO production secondary to induction of iNOS and activation of NF-κB. Moreover, LPS preconditioning increased the formation of pro-inflammatory cytokines, which is likely to have contributed to the observed aggravation of organ injury/dysfunction caused by HS.

• Authors: Regina Sordi, Fausto Chiazza, Nimesh S A Patel, Rachel A Doyle, Massimo Collino, Christoph Thiemermann
• Journal: PloS one (PLoS One) Vol. 10 Issue 4 Pg. e0122096 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 25830444 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Lipopolysaccharides
• NF-kappa B
• Nitric Oxide Synthase Type II
• Nos2 protein, rat

Topics

• Animals
• Cytokines (blood)
• Kidney (metabolism, pathology)
• Lipopolysaccharides (pharmacology)
• Liver (metabolism, pathology)
• Male
• NF-kappa B (metabolism)
• Nitric Oxide Synthase Type II (metabolism)
• Rats, Wistar
• Shock, Hemorrhagic (blood, immunology, pathology)