Korean J Pediatr.  2006 Mar;49(3):317-325. 10.3345/kjp.2006.49.3.317.

Effects of NG-monomethyl-L-arginine and L-arginine on cerebral hemodynamics and energy metabolism during reoxygenation-reperfusion after cerebral hypoxia-ischemia in newborn piglets

• Ko SY
• Kang S
• Chang YS
• Park EA
• Park WS

• KMID: 2278592
• DOI: http://doi.org/10.3345/kjp.2006.49.3.317

Abstract

PURPOSE: This study was carried out to elucidate the effects of nitric oxide synthase(NOS) inhibitor, NG-monomethyl-L-arginine(L-NMMA) and nitric oxide precursor, L-arginine(L-Arg) on cerebral hemodynamics and energy metabolism during reoxygenation-reperfusion(RR) after hypoxia-ischemia(HI) in newborn piglets.
METHODS
Twenty-eight newborn piglets were divided into 4 groups; Sham normal control(NC), experimental control(EC), L-NMMA(HI & RR with L-NMMA), and L-Arg(HI & RR with L-Arg) groups. HI was induced by occlusion of bilateral common carotid arteries and simultaneously breathing with 8 percent oxygen for 30 mins, and followed RR by release of carotid occlusion and normoxic ventilation for one hour. All groups were monitored with cerebral hemodynamics and cytochrome aa3 (Cyt aa3) using near infrared spectroscopy(NIRS). Na+, K(+)-ATPase activity, lipid peroxidation products, and tissue high energy phosphate levels were determined biochemically in the cerebral cortex.
RESULTS
In experimental groups, mean arterial blood pressure, PaO2, and pH decreased, and base excess and blood lactate level increased after HI compared to NC group(P<0.05). These variables subsequently returned to baseline after RR except pH. There were no differences among the experimental groups. In NIRS, oxidized hemoglobin(HbO2) decreased and hemoglobin(Hb) increased during HI(P<0.05) but returned to base line immediately after RR; 40 min after RR, the HbO2 had decreased significantly compared to NC group(P<0.05). Changes of Cyt aa3 decreased significantly compared to NC after HI and recovered at the end of the experiment. Significantly reduced cerebral cortical cell membrane Na+, K(+)-ATPase activity and increased lipid peroxidation products(P<0.05) were not improved with L-NMMA or L-Arg.
CONCLUSION
These findings suggest that NO is not involved in the mechanism of HI and RR brain damage during the early acute phase of RR.

Keyword

NG-monomethyl-l-arginine; L-arginine; Hypoxia; Ischemia; Perfusion; Injury; Energy metabolism; Brain

MeSH Terms

Anoxia
Arginine*
Arterial Pressure
Brain
Carotid Artery, Common
Cell Membrane
Cerebral Cortex
Electron Transport Complex IV
Energy Metabolism*
Hemodynamics*
Humans
Hydrogen-Ion Concentration
Hypoxia-Ischemia, Brain*
Infant, Newborn*
Ischemia
Lactic Acid
Lipid Peroxidation
Nitric Oxide
omega-N-Methylarginine*
Oxygen
Perfusion
Respiration
Ventilation
Arginine
Electron Transport Complex IV
Lactic Acid
Nitric Oxide
Oxygen
omega-N-Methylarginine