Effect of ifenprodil, a polyamine site NMDA receptor antagonist, on brain edema formation following asphyxial cardiac arrest in rats.
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.
Xiao
Feng
F
Department of Emergency Medicine, Louisiana State University Health Sciences Center in Shreveport, 1501 Kings Highway, Shreveport, LA 71130, USA. fxiao@lsuhsc.edu
Pardue
Sibile
S
Arnold
Thomas
T
Carden
Donna
D
Alexander
J Steven
JS
Monroe
Jared
J
Sharp
Christopher D
CD
Turnage
Richard
R
Conrad
Steven
S
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
D018691:Excitatory Amino Acid Antagonists; D010880:Piperidines; D011073:Polyamines; C010739:ifenprodil