title: Combining xenon and mild therapeutic hypothermia preserves neurological function after prolonged cardiac arrest in pigs.
abstract: OBJECTIVE
  Despite the introduction of mild therapeutic hypothermia into postcardiac arrest care, cerebral and myocardial injuries represent the limiting factors for survival after cardiac arrest. Administering xenon may confer an additional neuroprotective effect after successful cardiopulmonary resuscitation due to its ability to stabilize cellular calcium homeostasis via N-methyl-D-aspartate-receptor antagonism.
  
  
  METHODS
  In a porcine model, we evaluated effects of xenon treatment in addition to therapeutic hypothermia on neuropathologic and functional outcomes after cardiopulmonary resuscitation.
  
  
  METHODS
  Prospective, randomized, laboratory animal study.
  
  
  METHODS
  Fifteen male pigs.
  
  
  METHODS
  Following 10 mins of cardiac arrest and 6 mins of cardiopulmonary resuscitation, ten pigs were randomized to receive either mild therapeutic hypothermia (33°C for 16 hrs) or mild therapeutic hypothermia 1 xenon (70% for 1 hr). Five animals served as normothermic controls.
  
  
  RESULTS
  Gross hemodynamic variables were measured using right-heart catheterization. Neurocognitive performance was evaluated for 5 days after cardiopulmonary resuscitation using a neurologic deficit score before the brains were harvested for histopathological analysis. All animals survived the observation period in the mild therapeutic hypothermia 1 xenon group while one animal in each of the other two groups died. Mild therapeutic hypothermia 1 xenon preserved cardiac output during the induction of mild therapeutic hypothermia significantly better than did mild therapeutic hypothermia alone (4.6 6 0.6 L/min vs. 3.2 6 1.6 L/min, p # .05). Both treatment groups showed significantly fewer necrotic lesions in the cerebral cortex, caudate nucleus, putamen, and in hippocampal sectors CA1 and CA3/4. However, only the combination of mild therapeutic hypothermia and xenon resulted in reduced astrogliosis in the CA1 sector and diminished microgliosis and perivascular inflammation in the putamen. Clinically, only the mild therapeutic hypothermia 1 xenon-treated animals showed significantly improved neurologic deficit scores over time (day 1 = 59.0 6 27.0 vs. day 5 = 4.0 6 5.5, p ø .05) as well as in comparison to the untreated controls on days 3 through 5 after cardiopulmonary resuscitation.
  
  
  CONCLUSIONS
  These results demonstrate that even a short exposure to xenon during induction of mild therapeutic hypothermia results in significant improvements in functional recovery and ameliorated myocardial dysfunction.
authors.affiliation: Department of Surgical Intensive Care, University Hospital RWTH Aachen, Aachen, Germany. mfries@ukaachen.de
authors.forename: Michael
authors.initials: M
authors.lastname: Fries
authors.forename: Anne
authors.initials: A
authors.lastname: Brücken
authors.forename: Ayşegül
authors.initials: A
authors.lastname: Çizen
authors.forename: Maren
authors.initials: M
authors.lastname: Westerkamp
authors.forename: Céline
authors.initials: C
authors.lastname: Löwer
authors.forename: Jan
authors.initials: J
authors.lastname: Deike-Glindemann
authors.forename: Nora K
authors.initials: NK
authors.lastname: Schnorrenberger
authors.forename: Steffen
authors.initials: S
authors.lastname: Rex
authors.forename: Mark
authors.initials: M
authors.lastname: Coburn
authors.forename: Kay W
authors.initials: KW
authors.lastname: Nolte
authors.forename: Joachim
authors.initials: J
authors.lastname: Weis
authors.forename: Rolf
authors.initials: R
authors.lastname: Rossaint
authors.forename: Matthias
authors.initials: M
authors.lastname: Derwall
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D016887:Cardiopulmonary Resuscitation / Q000379:methods; D004195:Disease Models, Animal; D006323:Heart Arrest / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D007036:Hypothermia, Induced / Q000379:methods*; D002534:Hypoxia, Brain / Q000188:drug therapy / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D013552:Swine; D014978:Xenon / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D018696:Neuroprotective Agents; D014978:Xenon