Deep hypothermia diminishes the ischemic induction of heat-shock protein-72 mRNA in piglet brain.
OBJECTIVE
Expression of the 72-kD heat-shock protein (HSP72) has served as a useful indicator of ischemic stress after cerebral ischemia. Moderate hypothermia (30 degrees C) has been reported to block the induction of HSP72 after a brief episode of forebrain ischemia. The objective of the present study was to examine the effects of deep hypothermia (15 degrees C) on expression of HSP72 after a prolonged period of cerebral ischemia.


METHODS
Piglets 19 to 23 days old, were placed on cardiopulmonary bypass, and brain temperature was lowered to 23 degrees C (n = 9) or 15 degrees C (n = 9) before circulatory arrest for 1 hour. In an additional group of animals (n = 5), the temperature was lowered to 29 degrees C before arrest for 45 minutes. All animals were reperfused at 37 degrees C for 2 hours, and the regional expression of HSP72 mRNA was assessed using in situ hybridization.


RESULTS
After ischemia at 15 degrees C, expression of HSP72 mRNA was limited to a few scattered regions of cerebral cortex; the percentage of cortex exhibiting HSP72 mRNA was 23 +/- 7% (mean +/- SEM). Ischemia at 23 degrees C triggered expression of HSP72 mRNA in a significantly larger portion of the cortex (68 +/- 8%, P < .001). Ischemia at 29 degrees C failed to induce substantial expression of HSP72 mRNA in the cerebral cortex.


CONCLUSIONS
These results suggest that, relative to ischemia at 23 degrees C, deep hypothermia (15 degrees C) diminishes ischemic alterations leading to induction of HSP72 mRNA. The lack of cortical expression of HSP72 mRNA following ischemia at 29 degrees C may be secondary to inadequate recovery of energy metabolism.
Shaver
E G
EG
Division of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Welsh
F A
FA
Sutton
L N
LN
Mora
G
G
Gennarelli
L M
LM
Norwood
C R
CR
D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism; D001831:Body Temperature; D001921:Brain / Q000502:physiology; D002545:Brain Ischemia / Q000378:metabolism*; D002315:Cardiopulmonary Bypass; D002540:Cerebral Cortex / Q000378:metabolism; D004734:Energy Metabolism; D005786:Gene Expression Regulation; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism; D007036:Hypothermia, Induced; D017403:In Situ Hybridization; D015347:RNA Probes; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D015424:Reperfusion; D013552:Swine
D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D015347:RNA Probes; D012333:RNA, Messenger