Brain Oxidative Metabolism of the Newborn Dog: Correlation between31P NMR Spectroscopy and Pyridine Nucleotide Redox State

Abstract

The effects of both anoxia and short- and long-term hypoxia on brain oxidative metabolism were studied in newborn dogs. Oxidative metabolism was evaluated by two independent measures: in vivo continuous monitoring of mitochondrial NADH redox state and energy stores as calculated from the phosphocreatine (PCr)/Pilevels measured by31P nuclear magnetic resonance (NMR) spectroscopy. The hemodynamic response to low oxygen supply was further evaluated by measuring the changes in the reflected light intensity at 366 nm (the excitation wavelength for NADH). The animal underwent surgery and was prepared for monitoring of the two signals (NADH and PCr/Pi). It was then placed inside a Phosphoenergetics 260-80 NMR spectrometer magnet with a 31-cm bore. Each animal (1–21 days old) was exposed to short-term anoxia or hypoxia as well as to long-term hypoxia (1–2 h). The results can be summarized as follow: (a) In the normoxic brain, the ratio between PCr and Piwas > 1 (1.2–1.4), while under hypoxia or asphyxia a significant decrease that was correlated to the levels was recorded. (b) A clear correlation was found between the decrease in PCr/Pivalues and the increased redox state developed under decreased o2supply to the brain. (c) Exposing the animal to moderately long-term hypoxia led to a stabilized low-energy state of the brain with a good recovery after rebreathing normal air. (d) Under long-term and severe hypoxia, the microcirculatory autoregulatory mechanism was damaged and massive vasoconstriction was optically recorded simultaneously with a significant decrease in PCr/Pivalues. (e) The two techniques used simultaneously were complementary to each other and provided an excellent practical tool for brain energy metabolism evaluation.