title: Cecal inoculum peritonitis: An alternative model for sepsis vascular dysfunction study.
abstract: OBJECTIVE
  Sepsis is a life threatening condition that is characterized by the loss of vascular reactivity. The factor(s) responsible for the diminished vascular function seen in sepsis are not well understood. The purpose of this study was to characterize the vascular dysfunction from the rat cecal inoculum (CI) sepsis model using cecal ligation and puncture (CLP), and lipopolysaccharide (LPS) sepsis as reference models.
  
  
  METHODS
  Experiments were performed on isolated aorta from CI, CLP and LPS treated rats using a combination of pharmacological approaches.
  
  
  RESULTS
  Phenylephrine (PE)-induced aortic contraction was significantly decreased in each model (p<0.05) and not normalized by L-NAME or indomethacin. The vascular response elicited in the CI model for acetylcholine (Ach) was more similar to that seen in the CLP than the LPS model. The removal of the endothelial layer increased sensitivity to L-NAME (p<0.05) in aortae from CI group. Inhibition of the large conductance Ca(2+)/voltage sensitive K(+) (BKCa) channel did not normalize PE hyporesponsiveness but did abolish sepsis-induced contractile oscillation. Inhibition of the voltage dependent Kv1.5 channel was not able to reverse the vascular hyporesponsiveness, however, inhibition of the ATP dependent (KATP) channel inhibition partially restored the contractile response (p<0.05). Elevation of VCAM expression and aortic structural alternation were observed in each model.
  
  
  CONCLUSIONS
  These results suggest that the CI model may be an additional tool that could be used to investigate the mechanisms of vascular hyporesponsiveness in sepsis.
authors.affiliation: Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA; Department of Pharmaceutical Sciences and Research, School of Pharmacy, Marshall University, Huntington, WV, USA. Electronic address: sasano@hsc.wvu.edu.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Asano
authors.affiliation: Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA; Department of Pharmaceutical Sciences and Research, School of Pharmacy, Marshall University, Huntington, WV, USA; Department of Public Health, Marshall University, Huntington, WV, USA.
authors.forename: Nandini D P K
authors.initials: ND
authors.lastname: Manne
authors.affiliation: Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA.
authors.forename: Geeta
authors.initials: G
authors.lastname: Nandyala
authors.affiliation: Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA; Department of Pharmaceutical Sciences and Research, School of Pharmacy, Marshall University, Huntington, WV, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Ma
authors.affiliation: Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA; Department of Pharmaceutical Sciences and Research, School of Pharmacy, Marshall University, Huntington, WV, USA.
authors.forename: Vellaisamy
authors.initials: V
authors.lastname: Selvaraj
authors.affiliation: Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA.
authors.forename: Ravikumar
authors.initials: R
authors.lastname: Arvapalli
authors.affiliation: Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Rice
authors.affiliation: Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA; Department of Pharmaceutical Sciences and Research, School of Pharmacy, Marshall University, Huntington, WV, USA; Department of Pharmacology, Physiology and Toxicology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Blough
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002432:Cecum / Q000382:microbiology / Q000473:pathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D054086:KATP Channels / Q000187:drug effects; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects; D008026:Ligation; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010538:Peritonitis / Q000382:microbiology / Q000473:pathology*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000382:microbiology / Q000473:pathology*; D014652:Vascular Diseases / Q000382:microbiology / Q000473:pathology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D054086:KATP Channels; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008070:Lipopolysaccharides; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010656:Phenylephrine; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester
keywords: K(+) channel; Nitric oxide; Sepsis; Vascular inflammation