Depth of delayed cooling alters neuroprotection pattern after hypoxia-ischemia.
Hypothermia after perinatal hypoxia-ischemia (HI) is neuroprotective; the precise brain temperature that provides optimal protection is unknown. To assess the pattern of brain injury with 3 different rectal temperatures, we randomized 42 newborn piglets: (Group i) sham-normothermia (38.5-39 degrees C); (Group ii) sham-33 degrees C; (Group iii) HI-normothermia; (Group iv) HI-35 degrees C; and (Group v) HI-33 degrees C. Groups iii through v were subjected to transient HI insult. Groups ii, iv, and v were cooled to their target rectal temperatures between 2 and 26 hours after resuscitation. Experiments were terminated at 48 hours. Compared with normothermia, hypothermia at 35 degrees C led to 25 and 39% increases in neuronal viability in cortical gray matter (GM) and deep GM, respectively (both p < 0.05); hypothermia at 33 degrees C resulted in a 55% increase in neuronal viability in cortical GM (p < 0.01) but no significant increase in neuronal viability in deep GM. Comparing hypothermia at 35 and 33 degrees C, 35 degrees C resulted in more viable neurons in deep GM, whereas 33 degrees C resulted in more viable neurons in cortical GM (both p < 0.05). These results suggest that optimal neuroprotection by delayed hypothermia may occur at different temperatures in the cortical and deep GM. To obtain maximum benefit, you may need to design patient-specific hypothermia protocols by combining systemic and selective cooling.
Department of Paediatrics and Child Health, Royal Free and University College Medical School, The Rayne Institute, London, UK. oiwata@medphys.ucl.ac.uk
Osuke
O
Iwata
John S
JS
Thornton
Mark W
MW
Sellwood
Sachiko
S
Iwata
Yasuko
Y
Sakata
Martina A
MA
Noone
Frances E
FE
O'Brien
Alan
A
Bainbridge
Enrico
E
De Vita
Gennadij
G
Raivich
Donald
D
Peebles
Francesco
F
Scaravilli
Ernest B
EB
Cady
Roger
R
Ordidge
John S
JS
Wyatt
Nicola J
NJ
Robertson
D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D005260:Female; D007036:Hypothermia, Induced; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology* / Q000628:therapy*; D008297:Male; D009410:Nerve Degeneration / Q000517:prevention & control*; D009474:Neurons / Q000473:pathology*; D013552:Swine; D013696:Temperature