title: Effects of hypoxia-ischemia and inhibition of nitric oxide synthase on cerebral energy metabolism in newborn piglets.
abstract: The present study was designed to examine the effects of inhibition of nitric oxide synthase on cerebral energy metabolism after hypoxia-ischemia in newborn 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 normal saline (hypoxia, n = 5) 1 h before cerebral hypoxia-ischemia. After the infusion, hypoxia-ischemia was induced by bilateral occlusion of the carotid arteries and decreasing FiO2 to 0.07 and maintained for 60 min. Thereafter, animals were resuscitated and ventilated for another 3 h. Using 1H- and 31P-magnetic resonance spectroscopy, cerebral energy metabolism was measured in vivo at 15-min intervals throughout the experiment. Phosphocreatine 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 group) during hypoxia-ischemia. Thereafter, phosphocreatine to inorganic phosphate ratios returned rapidly to baseline values in the hypoxia group, but remained below baseline values in the NNLA-hypoxia group. Intracellular pH decreased during hypoxia-ischemia and returned to baseline values on reperfusion in both groups. Intracellular pH values were lower in the NNLA-hypoxia group (p < 0.001, ANOVA). Lactate was not present during the baseline period. After hypoxia-ischemia, lactate to N-acetylaspartate ratios increased to 1.34 +/- 0.28 (hypoxia group) and 2.22 +/- 0.46 (NNLA-hypoxia group). Lactate 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-acetylaspartate ratios (p < 0.001). Inhibition of nitric oxide synthase by NNLA tended to compromise cerebral energy status during and after cerebral hypoxia-ischemia in newborn piglets.
authors.affiliation: Department of Neonatology, Wilhelmina Children's Hospital, Utrecht University, The Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Groenendaal
authors.forename: R A
authors.initials: RA
authors.lastname: de Graaf
authors.forename: G
authors.initials: G
authors.lastname: van Vliet
authors.forename: K
authors.initials: K
authors.lastname: Nicolay
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000633:toxicity; D006863:Hydrogen-Ion Concentration; D002534:Hypoxia, Brain / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000633:toxicity; D010710:Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D013552:Swine
chemical_list: D004791:Enzyme Inhibitors; D010710:Phosphates; D010725:Phosphocreatine; D019335:Nitroarginine; D019344:Lactic Acid; D019001:Nitric Oxide Synthase