OBJECTIVES: 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. DISCUSSION: 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.
OBJECTIVES: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. DISCUSSION: 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.
Authors: José Guadalupe Soñanez-Organis; José Pablo Vázquez-Medina; Tania Zenteno-Savín; Andres Aguilar; Daniel E Crocker; Rudy M Ortiz Journal: J Exp Biol Date: 2012-05-01 Impact factor: 3.312