title: '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preconditioned with LPS (a) were not able to sustain a MAP at 30 mmHg for more than 50 min and (b) the volume of blood withdrawn in these animals was significantly less than in the PBS-control group.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.
  
  
  CONCLUSIONS
  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.affiliation: The William Harvey Research Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, London, United Kingdom; Capes Foundation, Ministry of Education of Brazil, Brasilia/DF, Brazil.
authors.forename: Regina
authors.initials: R
authors.lastname: Sordi
authors.affiliation: Department of Drug Science and Technology, University of Turin, Turin, Italy.
authors.forename: Fausto
authors.initials: F
authors.lastname: Chiazza
authors.affiliation: The William Harvey Research Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, London, United Kingdom.
authors.forename: Nimesh S A
authors.initials: NS
authors.lastname: Patel
authors.affiliation: The William Harvey Research Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, London, United Kingdom.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Doyle
authors.affiliation: Department of Drug Science and Technology, University of Turin, Turin, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Collino
authors.affiliation: The William Harvey Research Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, London, United Kingdom.
authors.forename: Christoph
authors.initials: C
authors.lastname: Thiemermann
mesh_terms: D000818:Animals; D016207:Cytokines / Q000097:blood; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D017208:Rats, Wistar; D012771:Shock, Hemorrhagic / Q000097:blood / Q000276:immunology* / Q000473:pathology
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat
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