title: Effect of ifenprodil, a polyamine site NMDA receptor antagonist, on brain edema formation following asphyxial cardiac arrest in rats.
abstract: OBJECTIVE
  Brain edema occurs in experimental and clinical cardiac arrest (CA) and is predictive of a poor neurological outcome. N-Methyl--aspartate (NMDA) receptors contribute to brain edema elicited by focal cerebral ischemia/reperfusion (I/R). Ifenprodil, a NMDA receptor antagonist, attenuates brain edema and injury size in rats after focal cerebral I/R. We assessed the hypothesis that ifenprodil reduces CA-elicited brain edema.
  
  
  METHODS
  Eighteen male Sprague-Dawley rats were assigned to group 1 (normal control, n=6), group 2 (placebo-treated CA, n=6), or group 3 (ifenprodil-treated CA, n=6). CA was induced by 8 min of asphyxiation and the animals were resuscitated with cardiopulmonary resuscitation (CPR), ventilation, epinephrine (adrenaline), and sodium bicarbonate (NaHCO3). Ifenprodil of 10 mg/kg or a placebo vehicle was given intraperitoneally 5 min before CA. Brain edema was determined by brain wet-to-dry weight ratio at 1 h after resuscitation.
  
  
  RESULTS
  There were no differences between groups 2 and 3 in all physiological variables at baseline. Time from asphyxiation to CA was 201.5 +/- 7.5 s in group 2 and 160.7 +/- 10.4 s in group 3 (P<0.001). Resuscitation time was 68.2 +/- 13.3 s in group 2 and 92.8 +/- 18.2 s in group 3 (P<0.05). Ifenprodil decreased mean arterial pressure (MAP) before asphyxiation, from 128 +/- 7 in group 2 to 82 +/- 15 mmHg in group 3 (P<0.001), and negated immediate post-resuscitation hypertension. Brain wet-to-dry weight ratio was 5.64 +/- 0.44 in group 1, 7.34 +/- 0.95 in group 2 (P<0.01 versus group 1), and 5.93 +/- 0.40 in group 3 (P<0.05 versus group 2).
  
  
  CONCLUSIONS
  Ifenprodil reduces CA-elicited brain edema. In addition, we observed significant hemodynamic changes caused by ifenprodil.
authors.affiliation: Department of Emergency Medicine, Louisiana State University Health Sciences Center in Shreveport, 1501 Kings Highway, Shreveport, LA 71130, USA. fxiao@lsuhsc.edu
authors.forename: Feng
authors.initials: F
authors.lastname: Xiao
authors.forename: Sibile
authors.initials: S
authors.lastname: Pardue
authors.forename: Thomas
authors.initials: T
authors.lastname: Arnold
authors.forename: Donna
authors.initials: D
authors.lastname: Carden
authors.forename: J Steven
authors.initials: JS
authors.lastname: Alexander
authors.forename: Jared
authors.initials: J
authors.lastname: Monroe
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Sharp
authors.forename: Richard
authors.initials: R
authors.lastname: Turnage
authors.forename: Steven
authors.initials: S
authors.lastname: Conrad
mesh_terms: D000818:Animals; D001237:Asphyxia / Q000150:complications*; D001929:Brain Edema / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D002545:Brain Ischemia / Q000150:complications*; D016887:Cardiopulmonary Resuscitation; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006324:Heart Arrest, Induced; D006439:Hemodynamics / Q000502:physiology; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D011073:Polyamines / Q000378:metabolism; D011336:Probability; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012680:Sensitivity and Specificity
chemical_list: D018691:Excitatory Amino Acid Antagonists; D010880:Piperidines; D011073:Polyamines; C010739:ifenprodil