Abstract
Newborn and 1-mo-old swine were exposed to identical durations (18 min) and degrees of hypoxia (O2 content = 4 mL/dL), to examine the effects of hypoxia on cerebral energy metabolism and intracellular pH (pHi)in vivo, using 31P and 1H nuclear magnetic resonance spectroscopy. Hypoxia produced the same extent of reductions in phosphocreatine (PCr) (63 ± 28% and 65 ± 10%, newborns and 1-mo-olds, respectively) and pHi (6.93 ± 0.06 and 6.89 ± 0.06, respectively) for either age group. The magnitude of changes in PCr, lactate, and pHi was larger for subgroups of data collected when cardiovascular instability was present, suggesting that hypotension and possibly reduced cerebral perfusion contributed to cerebral energy failure and lacticacidosis for either age group. There were no correlations between the blood plasma glucose concentration at 18 min of hypoxia and the extent of change in PCr, lactate, or pHi for either age group. During a subsequent period of complete ischemia induced via cardiac arrest after 20 min hypoxia, the decline in PCr and nucleoside triphosphate (NTP), and increase in lactate followed similar rates compared with previously studied age-matched animals that were normoxic before ischemia. The rate constants for the change in PCr, NTP, and lactate during ischemia showed no correlation with the blood plasma glucose concentration measured immediately before cardiac arrest. These results suggest that cerebral glycolytic rates and energy utilization during ischemia are unaffected by a preceding interval of hypoxia and that hyperglycemia does not delay cerebral energy failure during hypoxia or combined hypoxic-ischemia.
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Abbreviations
- AGR:
-
initial agonal glycolytic rate during complete ischemia
- Fio2:
-
fraction of inspired oxygen
- [glucose]plasma:
-
arterial blood plasma glucose concentration
- HR:
-
heart rate
- 1H NMR:
-
proton nuclear magnetic resonance
- klac:
-
first order rate constant for lactate accumulation
- Km:
-
blood plasma glucose concentration where glycolytic rate is half-maximal
- [lactate]final:
-
final postmortem brain lactate concentration
- [lactate]hypoxia:
-
brain lactate concentration at the end of hypoxia
- [lactate]plasma:
-
blood plasma lactate concentration
- MAP:
-
mean arterial blood pressure
- O2con:
-
blood oxygen content
- PCr:
-
phosphocreatine
- Pi:
-
inorganic phosphate
- Vmax:
-
maximum initial agonal glycolytic rate during complete ischemia
- FID:
-
free induction decay
- NTP:
-
nucleoside triphosphate
- pHa:
-
arterial pH
- pHi:
-
intracellular pH
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Supported by Grant-in-Aids 90G-075 and 92R-075 awarded by the American Heart Association Texas Affiliate, and Southwestern in Vivo Biotechnology Resource Facility Grant 5-P41-RR02584.
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Corbett, R., Laptook, A., Sterett, R. et al. Effect of Hypoxia on Glucose-Modulated Cerebral Lactic Acidosis, Agonal Glycolytic Rates, and Energy Utilization. Pediatr Res 39, 477–486 (1996). https://doi.org/10.1203/00006450-199603000-00016
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DOI: https://doi.org/10.1203/00006450-199603000-00016
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