title: Mimicry of human sepsis in a rat model--prospects and limitations.
abstract: BACKGROUND
  Sepsis and systemic inflammatory response syndrome (SIRS) continue to represent critical conditions with persistently high mortality and continue to need experimental and clinical research. We developed a rat model of gram-positive and gram-negative SIRS/sepsis with in vivo visualization of the pulmonary microcirculation to evaluate the optimal dosage and application path for SIRS/sepsis-inducing agents.
  
  
  METHODS
  Male Sprague-Dawley rats (n = 8 per group) were assigned to control, lipopolysaccharide (LPS), alphatoxin, or living Staphylococcus aureus (strain 68/50) groups. SIRS/sepsis was induced by intraperitoneal injection of the differing agents. The onset of SIRS was determined through human sepsis parameters and fluorescence video microscopy-based measurement of platelet and leukocyte velocity within the pulmonary vascular system (injection of 5 × 10(6) calcein AM-labeled nonactivated platelets; leukocytes labeled in vivo by rhodamine).
  
  
  RESULTS
  The optimal dosage to induce SIRS was 30 mg/250 g body weight for LPS (bolus injection) and 60 μg/250 g body weight for alphatoxin (2 h continuous perfusion). Sepsis was not achieved by injection of living S. aureus. The onset of SIRS was seen after 2-5 h for LPS and after 2-4 h for alphatoxin after intraperitoneal administration with a significantly increased heart rate, breathing rate, and body temperature (P < 0.05) and significantly decreased cell velocity (P < 0.05).
  
  
  CONCLUSIONS
  Our study represents an effective approach for a gram-negative (LPS) and gram-positive (alphatoxin) SIRS model to mimic human sepsis. Human sepsis-based criteria were used to define SIRS in our rats to achieve an optimal analogy for the human system. In our model, higher dosages were needed for SIRS induction than have been previously reported. The resulting, considerable heterogeneity of current SIRS-inducing models suggests that additional studies in this field are required to define standard procedures.
authors.affiliation: Department of General and Visceral Surgery, University Hospital of Muenster, Muenster, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Stahl
authors.forename: Bettina
authors.initials: B
authors.lastname: Löffler
authors.forename: Joerg
authors.initials: J
authors.lastname: Haier
authors.forename: Wolf Arif
authors.initials: WA
authors.lastname: Mardin
authors.forename: Soeren Torge
authors.initials: ST
authors.lastname: Mees
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000009:adverse effects; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000502:physiology; D006460:Hemolysin Proteins / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007274:Injections, Intraperitoneal; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000009:adverse effects; D008168:Lung / Q000098:blood supply / Q000503:physiopathology; D008297:Male; D008833:Microcirculation / Q000502:physiology; D018715:Microscopy, Video; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration; D018805:Sepsis / Q000097:blood / Q000209:etiology* / Q000503:physiopathology*; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood / Q000209:etiology* / Q000503:physiopathology*
chemical_list: D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D008070:Lipopolysaccharides; C021091:staphylococcal alpha-toxin