The effect of normothermic and hypothermic hypoxia-ischemia on brain hypoxanthine phosphoribosyl transferase activity.
OBJECTIVE
Cerebral hypoxia-ischemia leads to the depletion of ATP. Hypoxanthine, a degradation product of ATP, can be salvaged by hypoxanthine phosphoribosyl transferase (HPRT) and used to reform high-energy purines. Hypothermia conserves ATP in hypoxia-ischemia, possibly by preserving HPRT activity. We hypothesized that cerebral hypoxia-ischemia would decrease the activity of this enzyme, and that this reduction would be attenuated by moderate hypothermia.


METHODS
Three groups of rabbits were evaluated. Normothermic rabbits were exposed to 8 minutes of hypoxia, 8 minutes of cerebral ischemia, and 30 minutes or 4 hours of cerebral reperfusion. Hypothermic rabbits were cooled to a brain temperature of 33-34 degrees C throughout identical injury and reperfusion periods. Control rabbits underwent the same preparation, without hypothermia or injury. HPRT activity in the cortex, hippocampus, thalamus, caudate, and cerebellum was measured spectrophotometrically.


RESULTS
There were no significant differences (p>0.05) in enzymatic activity when comparing the three groups of animals, regardless of reperfusion time or brain temperature. Within the control group, some regional differences in enzyme activity were noted.


CONCLUSIONS
The results indicate that brain HPRT activity is unaffected by hypoxia-ischemia, even after 4 hours of reperfusion and regardless of brain temperature. This study supports the importance of this enzyme in the conservation of brain purines after neurologic injury.
Cherin
Tony
T
Department of Pediatrics, Division of Pediatric Critical Care, Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
Catbagan
Maria
M
Treiman
Stephen
S
Mink
Richard
R
D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D004195:Disease Models, Animal; D007035:Hypothermia; D007041:Hypoxanthine Phosphoribosyltransferase / Q000378:metabolism*; D020925:Hypoxia-Ischemia, Brain / Q000201:enzymology* / Q000473:pathology* / Q000503:physiopathology; D011817:Rabbits; D015424:Reperfusion / Q000379:methods; D013053:Spectrophotometry / Q000379:methods; D013696:Temperature; D013997:Time Factors
D007041:Hypoxanthine Phosphoribosyltransferase