title: The beneficial effects of acute hypercapnia on microcirculatory oxygenation in an animal model of sepsis are independent of K(+)ATP channels.
abstract: BACKGROUND
  Acute hypercapnia maintains the microcirculatory oxygenation of the splanchnic region during sepsis. The first aim of this study was to characterize the role of K(+)ATP channels on the microcirculatory flow and oxygenation during acute moderate hypercapnia. The second aim was to investigate whether a short period of hypercapnia induces detrimental effects in an otherwise undamaged rodent lung.
  
  
  METHODS
  Experiments were performed on 60 male Wistar rats. A moderate polymicrobial sepsis was induced by colon ascendens stent peritonitis (CASP) surgery. 24h after induction of sepsis volume-controlled and pressure-limited ventilation was established for 120 min, with either normocapnic (pCO2 35-45 mmHg) or moderate hypercapnic ventilation targets (pCO2 65-75 mmHg) and with or without non-selective K(+)ATP channel blockade with glibenclamide. Microcirculatory blood flow of the colonic wall as well as oxygen delivery and consumption were assessed with tissue laser Doppler and reflectance spectrophotometry. Hemodynamic variables were recorded and plasma cytokine levels and myeloperoxidase levels of the lungs were analyzed.
  
  
  RESULTS
  In septic animals microcirculatory oxygenation deteriorated progressively with normocapnia (-11.7 ± 11.8%) but was maintained (-2.9 ± 5.6%) with hypercapnia. This effect was associated with an increased microcirculatory oxygen consumption in septic animals with normocapnia (+25.7 ± 37.1%) that was decreased in the hypercapnia groups (-7.2 ± 28.1%). The effect of hypercapnia in septic animals was not altered by additional K(+)ATP channel blockade (-5.7 ± 32.7%). Hypercapnia neither induced an inflammatory response in lungs nor altered the systemic cytokine response.
  
  
  CONCLUSIONS
  The observed beneficial effect of hypercapnia on microvascular oxygenation of the colon in sepsis does not seem to be mediated via K(+)ATP channels.
authors.affiliation: Department of Anaesthesiology, University Hospital Duesseldorf, Germany.
authors.forename: Christopher
authors.initials: C
authors.lastname: Beck
authors.affiliation: Department of Anaesthesiology, University Hospital Duesseldorf, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Barthel
authors.affiliation: Department of Anaesthesiology, University Hospital Duesseldorf, Germany.
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Hahn
authors.affiliation: Department of Anaesthesiology, University Hospital Duesseldorf, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Vollmer
authors.affiliation: Department of Anaesthesiology, University Hospital Duesseldorf, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Herminghaus
authors.affiliation: Department of Anaesthesiology, University Hospital Duesseldorf, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Schäfer
authors.affiliation: Department of Anaesthesiology, University Hospital Duesseldorf, Germany.
authors.forename: Inge
authors.initials: I
authors.lastname: Bauer
authors.affiliation: Department of Anaesthesiology, University Hospital Duesseldorf, Germany. Electronic address: olaf.picker@med.uni-duesseldorf.de.
authors.forename: Olaf
authors.initials: O
authors.lastname: Picker
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D000818:Animals; D003106:Colon / Q000473:pathology; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D005905:Glyburide / Q000737:chemistry; D006439:Hemodynamics; D006935:Hypercapnia / Q000503:physiopathology*; D017078:Laser-Doppler Flowmetry; D008168:Lung / Q000378:metabolism; D008297:Male; D008833:Microcirculation; D010100:Oxygen / Q000737:chemistry*; D010101:Oxygen Consumption; D010538:Peritonitis / Q000503:physiopathology*; D009195:Peroxidase / Q000378:metabolism; D015221:Potassium Channels / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000503:physiopathology*
chemical_list: D016207:Cytokines; D015221:Potassium Channels; D000255:Adenosine Triphosphate; D009195:Peroxidase; D010100:Oxygen; D005905:Glyburide
keywords: Hypercapnia; K(+)(ATP); Oxygenation; Sepsis; Splanchnic microcirculation