The Changes of Cerebral Metabolic Parameters, Serum Levels of Neuron-Specific Enolase and S-100$\beta$ Protein During Retrograde Cerebral Perfusion Under Profound Hypothermic Total Circulatory Arrest

초저체온하 완전순환정지 시에 이용되는 역행성 뇌관류의 시간에 따른 뇌대사 지표, 혈청 내 neuron-specific enolase, 및 S-100 베타단백의 변화

  • 김경환 (흉부외과, 서울대학교 의과대학 흉부외과학교실)
  • Published : 2001.09.01

Abstract

Background: Retrograde cerebral perfusion(RCP) is one of the methods used for brain protection during aortic arch surgery. The author previously published the data, however, for the safety of it, there still remains many controversies. The author performed RCP and checked various parameters to clarify the possibility of early detection of cerebral injury. Material and Method: The author used pigs(Landrace species) weighing 25 to 30kg and performed RCP for 120 minutes. After weaning of cardiopulmonary bypass, we observed pigs for another 120 minutes. Rectal temperature, jugular venous oxygen saturation, central venous pressure were continuously monitored, and the hemodynamic values, histological changes, and serum levels of neuron-specific enolose(NSE) and S100$\beta$ protein were checked. Central venous pressure during RCP was maintained in the range of 20 to 25 mmHg. Result: Flow rates(ml/min) during RCP were 224.3$\pm$87.5(20min), 227.1$\pm$111.0(40min), 221.4$\pm$119.5(60min), 230.0$\pm$136.5(80min), 234.3$\pm$146.1(100min), and 184.3$\pm$50.5(120min). Serum levels of NSE did not increase after retrograde cerebral perfusion. Serum levels of S100$\beta$ protein(ng/ml) were 0.12$\pm$0.07(induction of anesthesia), 0.12$\pm$0.07(soon after CPB), 0.19$\pm$0.12(20min after CPB), 0.25$\pm$0.06(RCP 20min), 0.29$\pm$0.08(RCP 40min), 0.41$\pm$0.05(60min), 0.49$\pm$0.03(RCP 80min), 0.51$\pm$0.10(RCP 100min), 0.46$\pm$0.11(RCP 120min), 0.52$\pm$0.15(CPBoff 60min), 0.62$\pm$0.15(60min after rewarming), 0.76$\pm$0.17(CPBoff 30min), 0.81$\pm$0.20(CPBoff 60min), 0.84$\pm$0.23(CPBoff 90min) and 0.94$\pm$0.33(CPBoff 120min). The levels of S100$\beta$ after RCP were significantly higher than thosebefore RCP(p<0.05). The author could observe the mitochondrial swellings using transmission electron microscopy in neocortex, basal ganglia and hippocampus(CA1 region). Conclusion: The author observed the increase of serum S100$\beta$ after 120 minutes of RCP. The correlation between its level and brain injury is still unclear. The results should be reevaluated with longterm survival model also considering the confounding factors like cardiopulmonary bypass.

배경 : 역행성 뇌관류는 대동맥궁 수술에서 이용되는 뇌보호법중의 하나이다. 저자는 이에 대한 연구결과를 이미 발표한 바 있으나, 그 안전성 여부에 대하여는 아직 논의가 필요한 부분이다. 역행성 뇌관류 연구를 진행하면서, 조기 뇌손상을 시사한다고 알려진 여러 인자들을 조사하였다. 대상 및 방법 : 25~30kg 돼지를 이용하여 120분간 역행성 뇌관류를 시행하였다. 심폐기 이탈을 시행하고 2시간 동안 생존을 유도하였으며, 전기간에 걸쳐 직장체온, 내경정맥 산소포화도, 중심정맥압 등을 관찰하였다. 조직학적 소견을 관찰하였고, 혈중 neuron-specific enolose(NSE) 및 S100베타 단백치를 측정하였다. 역행성 뇌관류 시행 중 중심정맥압은 20~25mmHg를 유지하였다. 결과 : 역행성 뇌관류 속도 (ml/min)는 224.3$\pm$87.5(20분), 227.1$\pm$111.0(40분), 221.4$\pm$119.5(60분), 230.0$\pm$136.5(80분), 234.3$\pm$146.1(100분), 184.3$\pm$50.5(120분)으로 나타났으며 혈중 NSE 농도는 역행성 뇌관류 후에 관류전에 비해 유의한 증가를 보이지 않았다. 혈중 S100 베타 단백치(ng/ml)는 0.12$\pm$0.07(마취시작), 0.12$\pm$0.07(심폐바이패스직후), 0.19$\pm$0.12(심폐기가동 20분), 0.25$\pm$0.06(역행성뇌관류 20분), 0.29$\pm$0.08(40분), 0.41$\pm$0.05(60분), 0.49$\pm$0.03(80분), 0.51$\pm$0.10(100분), 0.46$\pm$0.11(120분), 0.52$\pm$0.15(심폐기 재가동 30분), 0.62$\pm$0.15(60분), 0.76$\pm$0.17(심폐기이탈 30분), 0.81$\pm$0.20(60분), 0.84$\pm$0.23(90분) and 0.94$\pm$0.33(120분)를 보였고 이는 역행성 뇌관류 전에 비해 유의하게 증가된 소견이었다(p<0.05). 뇌신피질, 기저핵, 해마에서 전자현미경 조직 소견을 관찰하였으며 마이토콘드리아의 부종을 관찰할 수 있었다. 결론 : 역행성 뇌관류 120분 후에 S100 베타 단백의 유의한 증가를 관찰할 수 있었으며 뇌조직 손상과의 관련성은 좀 더 연구되어야 할 부분으로 생각된다. 장기 생존 모델을 통한 재평가가 필요하다고 사료되며 심폐바이패스 시행 등의 교란 인자도 고려해야 할 것이다.

Keywords

References

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