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 hy pothermia after severe transient cerebral hypoxia-ischemia decreases t he severity of delayed energy failure in the newborn piglet. Six pigle ts underwent temporary occlusion of the common carotid arteries and hy poxemia. Resuscitation was started when cerebral [phosphocreatine (PCr )]/[inorganic phosphate (Pi)] as determined by phosphorus magnetic res onance spectroscopy had fallen almost to zero and [nucleotide triphosp hate (NTP)]/[exchangeable phosphate pool (EPP)] had fallen below about 30% of baseline. Rectal and tympanic temperatures were then reduced t o 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 pr eviously established data from 12 piglets similarly subjected to trans ient cerebral hypoxia-ischemia, but maintained normothermic, and six s ham-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 ag ain. Minimum values for these variables observed between 24 and 48 h w ere significantly higher in the hypothermic group and not significantl y different from the control values (p < 0.05, analysis of variance). A large reduction in secondary energy failure relative to the extent o f 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. We conclude that mild hypothermia after a severe acute cerebral hypoxic-i schemic insult ameliorated delayed energy failure.