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 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.
Groenendaal
F
F
Department of Neonatology, Wilhelmina Children's Hospital, Utrecht University, The Netherlands.
de Graaf
R A
RA
van Vliet
G
G
Nicolay
K
K
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
D004791:Enzyme Inhibitors; D010710:Phosphates; D010725:Phosphocreatine; D019335:Nitroarginine; D019344:Lactic Acid; D019001:Nitric Oxide Synthase