Effects of hypoxia-ischemia and inhibition of nitric oxide synthase on cerebral energy metabolism in newborn piglets

The present study was designed to examine the effects of inhibition of nitr ic oxide synthase on cerebral energy metabolism after hypoxia-ischemia in n ewborn piglets. Ten 1- to 3-d-old piglets received N-omega-nitro-L-arginine (NNLA), an inhibitor of nitric oxide synthase (NNLA-hypoxia, n = 5), or no rmal saline (hypoxia, n = 5) 1 h before cerebral hypoxia-ischemia. After th e infusion, hypoxia-ischemia was induced by bilateral occlusion of the caro tid arteries and decreasing Fio(2), to 0.07 and maintained for 60 min. Ther eafter, animals were resuscitated and ventilated for another 3 h. Using H-1 - and P-31-magnetic resonance spectroscopy, cerebral energy metabolism was measured in vivo at 15-min intervals throughout the experiment. Phosphocrea tine to inorganic phosphate ratios decreased from 2.74 +/- 0.14 to 0.74 +/- 0.36 (hypoxia group) and 2.32 +/- 0.17 to 0.18 +/-: 0.10 (NNLA-hypoxia gro up) during hypoxia-ischemia. Thereafter, phosphocreatine to inorganic phosp hate ratios returned rapidly to baseline values in the hypoxia group, but r emained below baseline values in the NNLA-hypoxia group. Intracellular pH d ecreased during hypoxia-ischemia and returned to baseline values on reperfu sion in both groups. Intracellular pH values were lower in the NNLA-hypoxia group (p < 0.001, ANOVA). Lactate was not present during the baseline peri od. After hypoxia-ischemia, lactate to N-acetylaspartate ratios increased t o 1.34 +/- 0.28 (hypoxia group) and 2.22 +/- 0.46 (NNLA-hypoxia group). Lac tate had disappeared after 3 h of reperfusion in the hypoxia group, whereas lactate to N-acetylaspartate ratios were 1.37 +/- 1.37 in the NNLA-hypoxia group. ANOVA demonstrated a significant effect of NNLA on lactate to N-ace tylaspartate ratios (p < 0.001). Inhibition of nitric oxide synthase by NNL A tended to compromise cerebral energy status during and after cerebral hyp oxia-ischemia in newborn piglets.