Mild hypothermia after severe transient hypoxia-ischemia ameliorates delayed cerebral energy failure in the newborn piglet.
Severely birth-asphyxiated human infants develop delayed ("secondary") cerebral energy failure, which carries a poor prognosis, during the first few days of life. This study tested the hypothesis that mild hypothermia after severe transient cerebral hypoxia-ischemia decreases the severity of delayed energy failure in the newborn piglet. Six piglets underwent temporary occlusion of the common carotid arteries and hypoxemia. Resuscitation was started when cerebral [phosphocreatine (PCr)]/[inorganic phosphate (Pi)] as determined by phosphorus magnetic resonance spectroscopy had fallen almost to zero and [nucleotide triphosphate (NTP)]/[exchangeable phosphate pool (EPP)] had fallen below about 30% of baseline. Rectal and tympanic temperatures were then reduced to 35 degrees C for 12 h after which normothermia (38.5 degrees C) was resumed. Spectroscopy results over the next 64 h were compared with previously established data from 12 piglets similarly subjected to transient cerebral hypoxia-ischemia, but maintained normothermic, and six sham-operated controls. The mean severity of the primary insult (judged by the time integral of depletion of [NTP]/[EPP]) was similar in the hypothermic and normothermic groups. In the normothermic group, [PCr]/[Pi] and [NTP]/[EPP] recovered after the acute insult and then fell again. Minimum values for these variables observed between 24 and 48 h were significantly higher in the hypothermic group and not significantly different from the control values (p < 0.05, analysis of variance). A large reduction in secondary energy failure relative to the extent of the primary insult was shown and no further fall in either [PCr]/[Pi] or [NTP]/[EPP] took place up to 64 h in the hypothermic piglets.(ABSTRACT TRUNCATED AT 250 WORDS)
Thoresen
M
M
Department of Paediatrics, University College London, United Kingdom.
Penrice
J
J
Lorek
A
A
Cady
E B
EB
Wylezinska
M
M
Kirkbride
V
V
Cooper
C E
CE
Brown
G C
GC
Edwards
A D
AD
Wyatt
J S
JS
D000208:Acute Disease; D000818:Animals; D000831:Animals, Newborn; D002540:Cerebral Cortex / Q000378:metabolism*; D004734:Energy Metabolism; D007036:Hypothermia, Induced; D002534:Hypoxia, Brain / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D002546:Ischemic Attack, Transient / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D010710:Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D013552:Swine
D010710:Phosphates; D010725:Phosphocreatine