Increased production of nitric oxide, a free radical with a potential for tissue damage, in cerebral tissue during hypoxia-ischemia (HI) and reperfusion has been demonstrated previously. The present study tests thehypothesis that inhibition of nitric oxide synthase (NOS) during cerebral HI reduces hypoxia-induced lactate production and changes in intracellular pH (pHi), phosphocreatine/ inorganic phosphate(PCr/Pi) ratios in cortical tissue of newborn piglets. Methods: Following anesthesia, 8 newborn piglets aged 1-3 days were instrumented, including placement of inflatable carotid occluders, and ventilated. The animals were placed in a 4.7 T magnet for examination of cerebral metabolism using 31P and 1H-MRS. Measurements were performed every 15 min throughout the experiment. One hour after the i.v. administration of 40 mg/kg Nω-nitro-L- arginine (n=4, NNLA-Hx group) or normal saline (n=4, Hx group), HI was induced by decreasing the FiO2 to 0.08 and carotid occlusion. After one hour, occluders were deflated, and resuscitation was started with an FiO2 sufficient to obtain PaO2 levels of 80-100 mmHg. pHi, PCr/Pi and lactate/N-acetylaspartate (Lac/NAA) ratios were calculated.Results: baseline pHi, PCr/Pi and Lac/NAA ratios(mean ± S.D.) were 7.22 ± 0.08, 2.80 ± 0.32, 0 in the Hx group and 7.12 ± 0.05, 2.46 ± 0.41, and 0 in the NNLA-Hx group, respectively (group differences not significant). After 1 hour of HI pHi, PCr/Pi and Lac/NAA were 6.79 ± 0.26, 1.13± 0.67, 1.10 ± 0.40 in the Hx group and 6.24 ± 0.31, 0.09± 0.06, and 2.07 ± 1.07 in the NNLA-Hx group. These differences are significant (P<0.05). Following 1 hour of resuscitation, pHi, PCr/Pi and Lac/NAA of the Hx group were 7.24 ± 0.18, 2.62 ± 0.36, and 0.34 ± 0.49, whereas in the NNLA-Hx group these values were 6.72 ± 0.44, 0.73 ± 0.93, and 1.11 ± 0.32, respectively. These differences are also significant (P<0.05).Conclusion: inhibition of NOS by NNLA during HI and reperfusion deteriorated cerebral energy metabolism in newborn piglets, which is in contrast with our hypothesis. We speculate that NO mediated effects on cerebral perfusion are important for cerebral energy metabolism following HI and reperfusion. Supported by the Wilhelmina Children's Hospital Research Fund
