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, Sun Young; Kang, Saem; Chang, Yun Sil; Park, Eun Ae; Park, Won Soon

Original Article

Korean Journal of Pediatrics 2006;49(3):317-325.
Published online March 15, 2006.

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

Sun Young Ko¹, Saem Kang², Yun Sil Chang³, Eun Ae Park⁴, Won Soon Park³

¹Department of Pediatrics, Samsung Cheil Hospital, Sungkyunkwan University School of Medicine
²Samsung Biomedical Institute
³Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
⁴Department of Pediatrics, College of Medicine, Ewha Womans University

급성 저산소성 허혈성 뇌손상이 유발된 신생자돈에서 재산소-재관류기 동안 NG-monomethyl-L-arginine과L-arginine이 뇌의 혈역학 및 에너지 대사에 미치는 영향

고선영^¹^, 강샘^²^, 장윤실^³^, 박은애^⁴^, 박원순^³

^¹성균관대학교 의과대학 삼성제일병원 소아과
^²삼성생명과학연구소
^³성균관대학교 의과대학 삼성서울병원 소아과
^⁴이화여자대학교 의과대학 소아과학교실

Correspondence:
Eun Ae Park, Email: pea8639@ewha.ac.kr

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.

Key Words: Infant , Small for gestational age , Growth hormone , Short stature