CEREBRAL METABOLIC RECOVERY FROM DEEP HYPOTHERMIC CIRCULATORY ARREST AFTER TREATMENT WITH ARGININE AND NITRO-ARGININE METHYL-ESTER

Recent studies suggest that nitric oxide is important in the pathogene sis of ischemic brain injury and also has a role in controlling cerebr ovascular tone, This study examines the net effects of nitric oxide on cerebral metabolic recovery after deep hypothermic circulatory arrest , Methods: Two-week-old piglets ere supported by cardiopulmonary bypas s and cooled to 15 degrees C followed by 1 hour of deep hypothermic ci rculatory arrest, 45 minutes of reperfusion and rewarming, and then 3 hours of normothermic perfusion, Groups of 10 piglets received one of four treatments before bypass: L-nitro-arginine methyl ester, inhibito r of nitric oxide synthesis, 10 mg/kg intravenous; L-arginine, to enha nce nitric oxide synthesis, 30 mg/kg intravenously before bypass and t hen 10 mg/kg per minute during the first hour of reperfusion; a combin ation of L-nitro-arginine methyl ester plus L-arginine at these same d oses; and no pretreatment (controls), Cerebral high-energy phosphates and pH were measured by magnetic resonance spectroscopy in half the an imals, Cerebral blood flow, metabolic rates for oxygen and glucose, an d the oxidation/reduction state of cytochrome aa3 and oxygenated and d eoxygenated hemoglobin measured by near-infrared spectroscopy were ass essed in the other half of the piglets, Results: L-nitro-arginine meth yl ester significantly increased cerebral vascular resistance and mark edly reduced recovery of high-energy phosphates, pH, and oxidation sta te of cytochrome aa3, L-arginine increased cerebral blood how, cerebra l glucose and oxygen consumption, and recovery of cytochrome aa3 oxida tion and high-energy phosphates, L-Arginine did not reverse completely the effects of L-nitro-arginine methyl ester on cerebral metabolic re covery, Conclusion: In a piglet model of deep hypothermic circulatory arrest, L-nitro-arginine methyl ester has a deleterious effect and L-a rginine has a beneficial effect on cerebral metabolic recovery, The de leterious metabolic effects of L-nitro-arginine methyl ester are only partially reversed by L-arginine. This fact suggests that there may be mechanisms in addition to inhibition of nitric oxide synthesis contri buting to the neurotoxicity of L-nitro-arginine methyl ester in this m odel.