Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
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Near-Infrared Spectroscopy for Monitoring Cerebral Hemodynamics in Hyperbilirubinemia-induced Newborn Piglets

고빌리루빈혈증이 유도된 신생자돈에서 근적외석 발광기를 이용한 뇌 혈역학적 변화에 대한 연구

  • Hwang, Jong Hee (Department of Pediatrics, Samsung Medical Center, College of Medicine, Sungkyunkwan University) ;
  • Choi, Chang Won (Department of Pediatrics, Samsung Medical Center, College of Medicine, Sungkyunkwan University) ;
  • Chang, Yun Sil (Department of Pediatrics, Samsung Medical Center, College of Medicine, Sungkyunkwan University) ;
  • Park, Won Soon (Department of Pediatrics, Samsung Medical Center, College of Medicine, Sungkyunkwan University)
  • 황종희 (성균관대학교 의과대학 삼성서울병원 소아과) ;
  • 최창원 (성균관대학교 의과대학 삼성서울병원 소아과) ;
  • 장윤실 (성균관대학교 의과대학 삼성서울병원 소아과) ;
  • 박원순 (성균관대학교 의과대학 삼성서울병원 소아과)
  • Received : 2004.12.30
  • Accepted : 2005.03.09
  • Published : 2005.06.15
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Abstract

Purpose : The present study examined how changes in cerebral hemodynamics in newborn piglets with bilirubin infusion can be evaluated by near infrared sepctroscopy(NIRS). Methods : Seventeen newborn piglets were randomly divided into the following three experimental groups : six in the control group(CG); seven in the bilirubin infusion group(BG), and four in the bilirubin infusion with 7-nitroindazole group(NG). To achieve the concentration of bilirubin above 20 mg/dL, we injected a bolus of 40 mg/kg of bilirubin intravenously, followed by 30 mg/kg/hr of bilirubin continuous intravenous infusion. All groups were monitored with cerebral hemodynamics using near infrared spectroscopy(NIRS) and their brain cortexes were harvested and the activities of $Na^+$, $K^+$-ATPase, level of conjugated dienes, ATP and phosphocreatine(PCr) were determined biochemically. Results : No changes took place in CG. In BG and NG, base excess, pH, and MABP decreased, and lactate level in blood increased. Cerebral $Na^+$, $K^+$-ATPase activity and ATP, PCr level in BG significantly decreased and conjugated dienes increased compared to CG. These abnormalities observed in the BG were significantly improved in the NG. In continuous NIRS monitoring, [$HbO_2$], [HbT], and [HbD] in BG were significantlly decreased compared to CG. However these abnormalities between NG and CG were not significantly different. There were no significant differences in $ScO_2$ between the study groups. Conclusion : Our study suggests cerebral hemodynamic changes could be monitored by non-invasive NIRS in newborn piglets with bilirubin infusion.

목 적 : 본 연구는 고빌리루빈혈증이 유도된 신생자돈에서 비 침습적인 NIRS을 통한 뇌의 혈역학적 변화에 대해 알아보고자 하였다. 방 법 : 17 마리의 신생자돈을 대상으로 정상 대조군(CG, n=6), 고빌리루빈혈증군(BG, n=7마리), 7-NI를 투여한 고빌리루빈 혈증군(NG, n=4)으로 무작위 구분하였다. 고빌리루빈혈증의 유도는 40 mg/kg의 빌리루빈을 농축괴로 정주한 후 곧 이어 30mg/kg/hr로 4시간 동안 지속 정주하여 혈중 빌리루빈 농도를 20 mg/dL 이상으로 유지하였고 7-NI는 빌리루빈을 농축괴로 투여한 전과 후에 50 mg/kg을 복막투여 하였다. 모든 실험군은 실험 기간 동안 뇌의 혈역학적 변화를 위해 NIRS로 감시하였고 뇌 조직을 적출하여 생화학적인 변화를 관찰하였다. 결 과 : 동맥혈의 base excss, pH, 평균 동맥압은 BG군과 NG군에서 CG군에 비해 유의하게 감소하였다. BG군에서 유의하게 뇌 조직의 $Na^+$, $K^+$-ATPase activity, ATP, PCr은 유의하게 감소하고 conjugated dienes는 유의하게 증가하였으나 NG 군은 이런 이상소견이 유의하게 완화되었다(P<0.05). 뇌 혈역학적 검사상 [$HbO_2$], [HbT], 및 [HbD]는 BG군에서 CG군에 비해 유의하게 감소하였고(P<0.05) NG군은 CG군과 차이가 없었다. 실험 종료시 $ScO_2$는 세 군간에 유의한 차이가 없었다. 결 론 : 고빌리루빈혈증이 유도된 신생자돈에서 뇌의 혈역학적인 변화를 비침습적인 NIRS의 감시를 통해 유용하게 관찰할 수 있었다.

Keywords

Acknowledgement

Supported by : 대한소아과학회

References

  1. Park WS, Chang YS, Lee M. Effect of 7-nitroindazole on bilirubin-induced changed in brain cell membrane function and energy metabolism in newborn piglets. Biol Neonate 2002;82:61-5 https://doi.org/10.1159/000064154
  2. Ochoa ELM, Wennberg R, An Y, Tandon T, Takashima T, Nguyen T, et al. Interactions of bilirubin with isolated presynaptic nerve terminals : functional effects on the uptake and release of neurotransmitters. Cell Mol Biol 1993;13:69-86
  3. Grojean S, Lievre V, Koziel V, Vert P, Daval J. Bilierubin exert additional toxic effects in hypoxic cultured neuron from the developing rat brain by the recruitment of glutamate neurotoxicity. Pediatr Res 2001;49:507-13 https://doi.org/10.1203/00006450-200104000-00012
  4. Brann BS, Stonestreet BS, Oh W, Cashore WJ. The in vivo effect of bilirubin and sulfisoxazole on cerebral oxygen, glucose, and lactate metabolsin in newborn piglets. Pediatr Res 1987;22:135-41 https://doi.org/10.1203/00006450-198708000-00006
  5. Hoffman DJ, Zanelli. SA, Kubin J, Mishra OP, Delivoriapapadopoulos. M. The in vivo effect of bilirubin on the Nmethyl-D-aspartate receptor/ion channel complex in the brains of newborn piglets. Pediatr Res 1996;40:804-8 https://doi.org/10.1203/00006450-199612000-00005
  6. Park WS, Chang YS, Chung SH, Seo DW, Hong SH, Lee M. Effect of hypothermia on bilirubin-induced alteration in brain cell membrane function and energy metabolism in newborn piglets. Brain Res 2001;922:276-81 https://doi.org/10.1016/S0006-8993(01)03186-9
  7. Hogg N, Kalyanaraman B. Nitric oxide and lipid peroxidation. Biochem Biophys Acta 1999;1411:378-84 https://doi.org/10.1016/S0005-2728(99)00027-4
  8. Dalkara T, Yoshida T, Irikura K. Moskowitz MA. Dual role of nitric oxide in pathophysiology of focal cerebral ischemia. Brain Pathol 1994;4:49-57 https://doi.org/10.1111/j.1750-3639.1994.tb00810.x
  9. Park WS. Clinical application of near infrared spectroscopy. J Korean Pediatr Soc 1996;39:595-602
  10. Park WS, Chang YS, Lee M. Kim KS, Shin SM, Choi JH. Delayed cerebral energy failure after acute hypoxic-ischemia in newborn piglet under 48hours of continuous monitoring using near-infrared spectroscopy. J Korean Pediatr Soc 1998;41:1198-1208
  11. Wyatt JS, Cope M, Delpy DT. Quantification of cerebral blood volume in human infants by near infrared spectroscopy. J Appl Physiol 1990;68:1086-91
  12. Wray SC, Cope M, Deply DT, Wyatt JS, Reynolds EOR. Characterization of the near infrared absorption spectra of cytochrome aa3 and hemoglobin for the non-invasive monitoring of cerebral oxygenation. Biochem Biophys Acta 1988; 933:184-92 https://doi.org/10.1016/0005-2728(88)90069-2
  13. Chang YS, Park WS, Lee M, Kim KS, Shin SM, Choi JH. Effect of hyperglycemia on brain cell membrane function and energy metabolism during hypoxic-ischemia in newborn piglets. Brain Res 1998;798:271-80 https://doi.org/10.1016/S0006-8993(98)00470-3
  14. Astrup J, Sorensen P, Sorensen H. Oxygen and glucose consumption related to $Na^+\;-K^+$ transport in canine brain. Stroke 1981;12:726-30 https://doi.org/10.1161/01.STR.12.6.726
  15. Schenker S, McCandless DW, Zollman PE. Studies of cellular toxicity of unconjugated bilirubin in kernicteric brain. J Clin Invest 1966;45:1210-3
  16. Lees GJ. Inhibition of sodium-potassium-ATPase : a potentially ubiquitous mechanism contributing to central nervous system neuropathology. Brain Res Rev 1991;16:283-300 https://doi.org/10.1016/0165-0173(91)90011-V
  17. Brown GC. Nitric oxide and mitochondrial respiration. Biochem Biophys Acta 1999;1411:351-69 https://doi.org/10.1016/S0005-2728(99)00025-0
  18. Tsuji M, Dulpessis A, Taylor G, Crocker R, Volpe J. Near infrared spectroscopy defects cerebral ischemic during hypotension in piglets. Pediatr Res 1998;44:591-5 https://doi.org/10.1203/00006450-199810000-00020
  19. Sienbenthal K, Bernert G, Casaer P. Near infrared spectroscopy in newborn infants. Brain Dev 1992;14:135-43 https://doi.org/10.1016/S0387-7604(12)80252-X
  20. Madsen PL, Skak C, Rasmussen A, Secher NH. Interference of ceebral near infrared oximetry in patients with icterus. Anesthesia and Analgesia 2000;90:489-95 https://doi.org/10.1097/00000539-200002000-00046
  21. Madsen PL, Secher NH. Near infrared oximetry in the brain. Progress in Neurobiology 1999;58:541-60 https://doi.org/10.1016/S0301-0082(98)00093-8
  22. Ives NK, Bolas NM, Gardnier RM. The effects of bilirubin on brain energy metabolism during hyperosmolar opening of the blood-brain barrier : an in vivo study using $^{31}P$ nuclear magnetic resonance spectroscopy. Pediatr Res 1989;26:356-61 https://doi.org/10.1203/00006450-198910000-00014