DELAYED (SECONDARY) CEREBRAL ENERGY FAILURE AFTER ACUTE HYPOXIA-ISCHEMIA IN THE NEWBORN PIGLET - CONTINUOUS 48-HOUR STUDIES BY PHOSPHORUS MAGNETIC-RESONANCE SPECTROSCOPY

Phosphorus (P-31) spectra from the brains of severely birth-asphyxiate d human infants are commonly normal on the first day of life. Later, c erebral energy failure develops, which carries a serious prognosis. Th e main purpose of this study was to test the hypothesis that this dela yed (''secondary'') energy failure could be reproduced in the newborn piglet after a severe acute reversed cerebral hypoxicischemic insult. Twelve piglets were subjected to temporary occlusion of the common car otid arteries and hypoxemia [mean arterial Po-2 3.1 (SD 0.6) kPa]. Mea n cerebral phosphocreatine concentration [PCr]/inorganic orthophosphat e concentration [Pi] decreased from 1.40 (SD 0.29) to 0.01 (SD 0.02), and nucleotide triphosphate concentration [NTP]/exchangeable phosphate pool concentration [EPP] decreased from 0.19 (SD 0.02) to 0.06 (SD 0. 04) (p < 0.001 for each decrease). On reperfusion and reoxygenation of the brain, mean [PCr]/[Pi] and [NTP]I[EPP] returned to baseline. Obse rvations continuing for the next 48 h showed that [PCr]/[Pi] again dec reased, in spite of normal arterial Po,, mean arterial blood pressure, and blood glucose, to 0.62 (SD 0.61) at 24 h (p < 0.01) and 0.49 (SD 0.37) at 48 h (p < 0.001). [NTP]/[EPP] also decreased, but to a lesser degree. Intracellular pH remained unchanged. These findings appeared identical with those seen in birth-asphyxiated human infants. No chang es in cerebral metabolite concentrations took place in six control pig lets. The severity of secondary energy failure, as judged by the lowes t [PCr]/[Pi] recorded at 24-48 h, was directly related to the extent o f acute energy depletion, obtained as the time integral of reduction i n [NTP]/[EPP] (p < 0.0001). This animal model of secondary energy fail ure may prove useful for testing cerebroprotective strategies.