title: Hypothermia improves oral and gastric mucosal oxygenation during hypoxic challenges.
abstract: BACKGROUND
  Therapeutic hypothermia, used primarily for protective effects after hypoxia, improves oral and gastric mucosal microvascular oxygenation (μHbO₂) during additional haemorrhage. Therefore, we questioned whether hypothermia likewise improves μHbO₂ during hypoxic challenges. Since both hypothermia and hypoxia reduce cardiac output (e.g. by myofilament Ca(2+) desensitization), and modulate vasomotor tone via K(+) ATP channels, we hypothesized that the Ca(2+) sensitizer levosimendan and K(+) ATP channel blocker glibenclamide would support the cardiovascular system.
  
  
  METHODS
  The effects of mild hypothermia (34°C) on μHbO₂ during hypoxia [Formula: see text] were analysed in a cross-over study on five anaesthetized dogs and compared with normothermia (37.5°C) and hypoxia. During hypothermia, but before hypoxia, glibenclamide (0.2 mg kg(-1)) or levosimendan (20 µg kg(-1)+0.25 µg kg(-1) min(-1)) was administered. Systemic haemodynamic variables, gastric and oral mucosal microvascular oxygenation (reflectance spectrophotometry), and perfusion (laser Doppler flowmetry) were recorded continuously. Data are presented as mean (sem), P<0.05.
  
  
  RESULTS
  Hypoxia during normothermia reduced gastric μHbO₂ by 27 (3)% and oral μHbO₂ by 28 (3)% (absolute change). During hypothermia, this reduction was attenuated to 16 (3)% and 13 (1)% (absolute change). This effect was independent of microvascular flow that did not change during hypoxia and hypothermia. Additional administration of levosimendan during hypothermia restored reduced cardiac output but did not change flow or μHbO₂ compared with hypothermia alone. Glibenclamide did not exert any additional effects during hypothermia.
  
  
  CONCLUSIONS
  Hypothermia attenuates the decrease in μHbO₂ during additional hypoxic challenges independent of systemic or regional flow changes. A reduction in cardiac output during hypothermia is prevented by Ca(2+) sensitization with levosimendan but not by K(+) ATP channel blockade with glibenclamide.
authors.affiliation: Department of Anaesthesiology, University Hospital Duesseldorf, Moorenstrasse 5, 40225 Duesseldorf, Germany christian.vollmer@uni-duesseldorf.de.
authors.forename: C
authors.initials: C
authors.lastname: Vollmer
authors.affiliation: Department of Anaesthesiology, University Hospital Duesseldorf, Moorenstrasse 5, 40225 Duesseldorf, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Weiß
authors.affiliation: Department of Anaesthesiology, University Hospital Duesseldorf, Moorenstrasse 5, 40225 Duesseldorf, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Beck
authors.affiliation: Department of Anaesthesiology, University Hospital Duesseldorf, Moorenstrasse 5, 40225 Duesseldorf, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Bauer
authors.affiliation: Department of Anaesthesiology, University Hospital Duesseldorf, Moorenstrasse 5, 40225 Duesseldorf, Germany.
authors.forename: O
authors.initials: O
authors.lastname: Picker
mesh_terms: D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology; D018592:Cross-Over Studies; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D005753:Gastric Mucosa / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D005905:Glyburide / Q000494:pharmacology; D006835:Hydrazones / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007036:Hypothermia, Induced / Q000379:methods*; D000860:Hypoxia / Q000188:drug therapy / Q000378:metabolism*; D017078:Laser-Doppler Flowmetry / Q000379:methods; D008833:Microcirculation / Q000187:drug effects; D009061:Mouth Mucosa / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D011724:Pyridazines / Q000494:pharmacology; D000077464:Simendan
chemical_list: D002316:Cardiotonic Agents; D006835:Hydrazones; D007004:Hypoglycemic Agents; D011724:Pyridazines; D000077464:Simendan; D010100:Oxygen; D005905:Glyburide
keywords: gastrointestinal tract; glibenclamide; hypothermia, induced; hypoxia; levosimendan; microcirculation; mucosa