title: Delayed, spontaneous hypothermia reduces neuronal damage after asphyxial cardiac arrest in rats.
abstract: OBJECTIVE
  Core temperature is reduced spontaneously after asphyxial cardiac arrest in rats. To determine whether spontaneous hypothermia influences neurologic damage after asphyxial arrest, we compared neurologic outcome in rats permitted to develop spontaneous hypothermia vs. rats managed with controlled normothermia.
  
  
  METHODS
  Male Sprague-Dawley rats were asphyxiated for 8 mins and resuscitated. After extubation, a cohort of rats was managed with controlled normothermia (CN) by placement in a servo-controlled incubator set to maintain rectal temperature at 37.4 degrees C for 48 hrs. CN rats were compared with permissive hypothermia (PH) rats that were returned to an ambient temperature environment after extubation. Rats were killed at either 72 hrs (PH72hr, n = 14; CN72hr, n = 9) or 6 wks (PH6wk, n = 6, CN6wk, n = 6) after resuscitation. PH72 rats were historic controls for the CN72 rats, whereas PH6 and CN6 rats were randomized and studied contemporaneously.
  
  
  METHODS
  A clinical neurodeficit score (NDS) was determined daily. A pathologist blinded to group scored 40 hematoxylin and eosin -stained brain regions for damage by using a 5-point scale (0 = none, 5 = severe). Quantitative analysis of CA1 hippocampus injury was performed by counting normal-appearing neurons in a defined subsection of CA1.
  
  
  RESULTS
  Mean rectal temperatures measured in the PH6wk rats (n = 6) were 36.9, 34.8, 35.5, 36.7, and 37.4 degrees C at 2, 8, 12, 24, and 36 hrs, respectively. Mortality rate (before termination) was lower in PH compared with CN (0/20 vs. 7/15; p < .005). PH demonstrated a more favorable progression of NDS (p = .04) and less weight loss (p < .005) compared with CN. Median histopathology scores were lower (less damage) in PH72hr vs. CN72hr for temporal cortex (0 vs. 2.5), parietal cortex (0 vs. 2), thalamus (0 vs. 3), CA1 hippocampus (1.5 vs. 4.5), CA2 hippocampus (0 vs. 3.5), subiculum (0 vs. 4), and cerebellar Purkinje cell layer (2 vs. 4) (all p < .05). There was almost complete loss of normal-appearing CA1 neurons in CN72hr rats (6 +/- 2 [mean +/- SD] normal neurons compared with 109 +/- 12 in naïve controls). In contrast, PH72hr rats demonstrated marked protection (97 +/- 23 normal-appearing neurons) that was still evident, although attenuated, at 6 wks (42 +/- 24 normal-appearing neurons, PH6wk).
  
  
  CONCLUSIONS
  Rats resuscitated from asphyxial cardiac arrest develop delayed, mild to moderate, prolonged hypothermia that is neuroprotective.
authors.affiliation: Division of Pediatric Emergency Medicine, Children's Hospital of Pittsburgh, PA 15213-2583, USA.
authors.forename: R W
authors.initials: RW
authors.lastname: Hickey
authors.forename: H
authors.initials: H
authors.lastname: Ferimer
authors.forename: H L
authors.initials: HL
authors.lastname: Alexander
authors.forename: R H
authors.initials: RH
authors.lastname: Garman
authors.forename: C W
authors.initials: CW
authors.lastname: Callaway
authors.forename: S
authors.initials: S
authors.lastname: Hicks
authors.forename: P
authors.initials: P
authors.lastname: Safar
authors.forename: S H
authors.initials: SH
authors.lastname: Graham
authors.forename: P M
authors.initials: PM
authors.lastname: Kochanek
mesh_terms: D000818:Animals; D001237:Asphyxia / Q000150:complications*; D001831:Body Temperature; D004195:Disease Models, Animal; D006323:Heart Arrest / Q000150:complications*; D007035:Hypothermia / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D002534:Hypoxia, Brain / Q000209:etiology* / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation; D016037:Single-Blind Method; D013997:Time Factors