Hypothermia for 24 hours after asphyxic cardiac arrest in piglets provides striatal neuroprotection that is sustained 10 days after rewarming.
The neuroprotective effect of hypothermia instituted after resuscitation from asphyxic cardiac arrest has not been studied in immature brain, particularly in a large animal model with recovery periods greater than 4 d. Moreover, protection from severe hypoxia seen with 3 h of hypothermia was reported to be lost when hypothermic duration was extended to 24 h in unsedated piglets, in contrast to the neuroprotection reported by 72 h of intrauterine head cooling in fetal sheep. Piglets (5-7 postnatal days) were subjected to asphyxic cardiac arrest followed by 24 h of either hypothermia (34 degrees C) or normothermia (38.5-39 degrees C). Comparisons were made with normothermic and hypothermic surgical sham animals without asphyxia. All of these groups were sedated, paralyzed, and mechanically ventilated for the first 24 h to prevent shivering and possible depletion of glucose stores. Hypothermia per se did not cause remarkable structural abnormalities. Ischemic damage was evaluated in putamen at 1 d of recovery without rewarming and at 11 d (10 d +/- SD after rewarming). Ischemic cytopathology affected 60 +/- 12% of neurons in putamen of normothermic animals compared with 9 +/- 6% in hypothermic animals at 1 d of recovery without rewarming. At 11 d of recovery from hypoxia-ischemia, the density of viable neurons (neuron profiles/mm2) in putamen was markedly reduced in normothermic animals (81 +/- 40) compared with hypothermic animals (287 +/- 22), which was the same as in sham normothermic (271 +/- 21), sham hypothermic (288 +/- 46) and naïve animals (307 +/- 51). These data demonstrate that 24 h of hypothermia at 34 degrees C with sedation and muscle relaxation after asphyxic cardiac arrest prevents necrotic striatal neuronal cell death in immature brain before rewarming, and that the effect is sustained at 11 d after injury without deleterious side effects.
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Hospital, Blalock 1404, 600 N. Wolfe Street, Baltimore, MD 21287 U.S.A. rkoehler@jhmi.edu
Dawn M
DM
Agnew
Raymond C
RC
Koehler
Anne-Marie
AM
Guerguerian
Donald H
DH
Shaffner
Richard J
RJ
Traystman
Lee J
LJ
Martin
Rebecca N
RN
Ichord
D000208:Acute Disease; D000818:Animals; D001237:Asphyxia / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D001522:Behavior, Animal; D001831:Body Temperature; D003342:Corpus Striatum / Q000473:pathology* / Q000502:physiology; D004569:Electroencephalography; D006323:Heart Arrest / Q000401:mortality / Q000469:parasitology / Q000628:therapy*; D006358:Hot Temperature; D007036:Hypothermia, Induced; D008297:Male; D009336:Necrosis; D012007:Rectum; D013552:Swine; D015430:Weight Gain