• Journal of Chest Surgery
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• v.35 no.10
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• pp.712-723
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• 2002

Substantial alterations in cerebral blood flow(CBF) are known to occur during cardiopulmonary bypass(CPB). Many investigators have speculated that these changes may be responsible for both minor and major cerebral damages after CPB. More recently, these changes in CBF have been observed to be intimately related to the arterial carbon dioxide tension(Pa$CO_2$) maintained during CPB. The present study was prospectively designed to investigate the clinical effects of normocapnic and hypercapnic CPB on the cerebral oxygen metabolism in cardiac surgery Material and Method: Thirty-six adult patients scheduled for elective cardiac surgery were randomized to either normocapnic group (Pa$CO_2$35~40 mmHg, n＝18) or hypercapnic group(Pa$CO_2$, 45~55 mmHg, n＝18) with moderately hypothermic nonpulsatile CPB(nasopharyngeal temperature of 29~3$0^{\circ}C$). In each patient, middle cerebral artery blood flow velocity( $V_{MCA}$), cerebral arteriovenous oxygen content difference (C(a-v) $O_2$), cerebral oxygen extraction(COE), cerebral metabolic rate for oxygen(CMR $O_2$), cerebral oxygen transport( $T_{E}$ $O_2$), $T_{E}$ $O_2$/CMR $O_2$ ratio, cerebral desaturation(internal jugular bulb blood oxygen saturation $\leq$ 50%), and arterial and jugular bulb blood gas were evaluated throughout the operation. Postoperative neuropsychologic complications were assessed in all patients. All variables were compared between the two groups. Result: VMCA(169.13 $\pm$ 8.32 vs 153.11 $\pm$8.98%), TE $O_2$(1,911.17$\pm$250.14 vs 1,757.40$\pm$249.56), $T_{E}$ $O_2$,/CMR $O_2$ ratio(287.38$\pm$28.051 vs 246.77$\pm$25.84), $O_2$ tension in internal jugular bulb (41.66$\pm$9.19 vs 31.50$\pm$6.09 mmHg), and $O_2$saturation in internal jugular bulb(68.97$\pm$10.96 vs 58.12$\pm$12.11%) during CPB were significantly lower in normocapnic group(p＝0.03), whereas hypercapnic group had lower C(a-v) $O_2$(3.9$\pm$0.3 vs 4.9$\pm$0.3 mL/dL), COE(0.3$\pm$0.03 vs 0.4$\pm$0.03), CMR $O_2$(5.8 $\pm$0.5 vs 6.8$\pm$0.6), and arterial blood pH(7.36$\pm$0.09 vs 7.46$\pm$0.07, p＝0.04) during CPB. Hypercapnic group had lower incidence of cerebral desaturation than normocapnic group(3 vs 9 patients, p=0.03). Duration of the neuropsychologic complication(delirium) were shorter in hypercapnic group than in normocapnic group(36 vs 60 hrs, p＝0.009). Conclusion: These findings suggest that hypercapnic CPB may have salutary effects on the cerebral oxygen metabolism and postoperative neurologic outcomes in cardiac surgery.surgery.

• Clinical and Experimental Pediatrics
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• v.45 no.5
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• pp.560-567
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• 2002

주산기 뇌손상은 주로 급격한 저산소-허혈 손상에 의하는데 급격한 산소 공급의 차단은 oxidative phosphorylation을 정지 시켜서 뇌대사를 위한 에너지 공급이 차단되게 된다. 에너지 공급이 차단된 뇌세포는 뇌세포막에서 세포 내외의 이온 농도 차를 유지시키던 ATP-dependent $Na^{+}-K^{+}$ pump의 기능이 정지 되고, 세포 내외의 농도 차에 따라 $Na^{+}$, $Cl^{+}$, $Ca^{{+}{+}}$의 대규모 세포 내로 이동이 일어난다. 세포 내로 calcium 이온의 이동은 glutamate 수용체의 활성화에 의해서도 일나는데, 세포 내 calcium 이온의 증가는 protease, lipase, nuclease 등을 활성화 시켜 세포를 사망에 이르게 하는 연속적이고 다양한 생화학적 반응을 일으키게 된다. Glutamate는 대표적인 신경 전달 물질인데 저산소-허혈 손상 시 glutamate 수용체의 지나친 흥분은 미성숙 뇌에 뇌손상을 유발하는데, NMDA 또는 non-NMDA 수용체와 복합체를 형성하고 있는 calcium 이동 통로를 활성화 시켜 세포 내 calcium 이온을 증가시키고, 그 외에 metabotropic recetor는 G-protein의 활성화 등을 통해 뇌손상을 유발하는 다양한 생화학적 반응을 매개한다. 저산소-허혈 손상 후 재산소화와 재관류가 일어나면서 뇌세포의 지연성 사망(secondary neuronal death)이 일어나는데 이는 초기 손상 후 뒤이어 일어나는 다양한 생화학적 반응에 의하는데 다량의 산소 자유기 발생, nitric oxide의 생성, 염증 반응과 싸이토카인, 신경전도 물질의 과흥분 등이 관여하며, 신경 세포 사망은 세포괴사(necrosis)뿐 아니라 일부는 세포 사멸(apoptosis)로 알려진 의도된 세포 사망(programmed cell death)에 의한 것으로 생각되고 있다(Fig. 2).

• Clinical and Experimental Pediatrics
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• v.52 no.1
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• pp.105-110
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• 2009

Purpose : Perinatal asphyxia is an important cause of neonatal mortality and subsequent lifelong neurodevelopmental handicaps. Although many treatment strategies have been tested, there is currently no clinically effective treatment to prevent or reduce the harmful effects of hypoxia and ischemia in humans. Erythropoietin (Epo) has been shown to exert neuroprotective effects in various brain injury models although the exact mechanisms through which Epo functions are not completely understood. This study investigates the effect of Epo on hypoxic-ischemic (HI) brain injury and the possibility that its neuroprotective actions may be associated with iron-mediated metabolism. Methods : HI brain injury was produced in 7-day-old rats by unilateral carotid artery ligation followed by hypoxia with 8% oxygen for 2 h. At the end of HI brain injury, the rats received an intraperitoneal injection of 5,000 units/kg erythropoietin. Random premedication with iron, deferoxamine, iron-deferoxamine, or saline were performed 23 d before HI brain injury. The severity of the brain injury was assessed at 7 d after HI. Results : Single Epo treatment post-HI brain injury reduced the gross and histopathological findings of brain injury. Iron premedication did not increase the incidence or severity of the injury as measured by the damage score. Deferoxamine administration before HI brain injury improved the brain injury as compared to no treatment or Epo treatment. Conclusion : These findings indicate that Epo provides neuroprotective benefits after HI in the developing brain. These findings suggest that Epos neuroprotective actions may involve reducing iron in tissues that mediate the formation of free radicals.

• Journal of Chest Surgery
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• v.36 no.7
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• pp.472-482
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• 2003

Recent studies have demonstrated that cerebral desaturation during rewarming period of CPB was associated with postoperative neurologic dysfunction. The prevention of cerebral desaturation during CPB may reduce the incidences of neurologic and neuropsychological complications. The present study was prospectively undertaken to compare the clinical effects between two strategies (hypercapnic CPB and high flow CPB) to prevent cerebral desaturation for establishing a proper CPB technique. Material and Method: Thirty-six adult patients scheduled for elective cardiac surgery were randomized into either hypercapnic (Pa$CO_2$ 45~50mmHg, n＝18) or high flow group (flow rate 2.75 L/ $m^2$/min and Pa$CO_2$ 35~40mmHg, n＝18) during rewarming period of CPB. In each patient, middle cerebral artery blood flow velocity ( $V_{MCA}$), cerebral arteriovenous oxygen content difference (C(a-v) $O_2$), modified cerebral metabolic rate for oxygen (MCMR $O_2$), cerebral oxygen transport rate ( $T_{E}$ $O_2$), incidence of cerebral desaturation (internal jugular bulb blood oxygen saturation $\leq$ 50%), increased rate of S-100 $\beta$ concentration, and arterial and internal jugular bulb blood gas were measured during the five phases of the operation; Pre-CPB, CPB-10 min (steady-state CPB, nasopharyngeal temperature 29~3$0^{\circ}C$), Rewarm-1 (rewarming phase, nasopharyngeal temperature 33$^{\circ}C$), Rewarm-2 (nasopharyngeal temperature 37$^{\circ}C$), and CPB-off. Incidence of postoperative delirium and duration were assessed in all patients. All variables were compared between the two groups. Result: $V_{MCA}$ (157.88$\pm$10.87 vs 120.00$\pm$6.18%, p＝0.006), internal jugular bulb $O_2$ saturation (68.01$\pm$2.75 vs 61.28$\pm$2.87%, p＝0.03) and $O_2$ tension (41.01$\pm$2.25 vs 32.02$\pm$ 1,67 mmHg, p＝0.03), and $T_{E}$ $O_2$(110.84$\pm$7.41 vs 81.15$\pm$8.11%, p＝0.003) at rewarming periods were higher in the hypercapnic group than in the high flow group. C(a-v) $O_2$ (4.0$\pm$0.30 vs 4.84$\pm$0.38 mg/dL, p＝0.04), COE (0.36$\pm$0.03 vs 0.42$\pm$0.03, p＝0.04), increased rate of S- 100$\beta$ (391.67$\pm$23.40 vs 940.0$\pm$17.02%, p＝0.003), and incidence of cerebral desaturation (2 vs 4 patients, p＝0.04) at rewarming periods, and duration of postoperative delirium (18 vs 34 hr, p＝0.02) were low in the hypercapnic group compared to the high flow group. Conclusion: These results indicate that hypercapnic CPB may provide relatively diminished cerebral injury and beneficial effects for cerebral metabolism relatively compared to high flow CPB.low CPB.

• Journal of Chest Surgery
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• v.35 no.6
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• pp.420-429
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• 2002

Moderate hypothermic cardiopulmonary bypass (CPB) has commonly been used in cardiac surgery. Several cardiac centers recently practice normothermic CPB in cardiac surgery, However, the clinical effect and safety of normothermic CPB on cerebral metabolism are not established and not fully understood. This study was prospectively designed to evaluate the clinical influence of normothermic CPB on brain metabolism and to compare it with that of moderate hypothermic CPB. Material and Method: Thirty-six adult patients scheduled for elective cardiac surgery were randomized to receive normothermic (nasopharyngeal temperature ＞34.5 $^{\circ}C$, n=18) or hypothermic (nasopharyngeal temperature 29~3$0^{\circ}C$, n=18) CPB with nonpulsatile pump. Middle cerebral artery blood flow velocity (VMCA), cerebral arteriovenous oxygen content difference (CAVO$_{2}$), cerebral oxygen extraction (COE), modified cerebral metabolic rate for oxygen (MCMRO$_{2}$), cerebral oxygen transport (TEO$_{2}$), cerebral venous desaturation (oxygen saturation in internal jugular bulb blood$\leq$50 %), and arterial and internal jugular bulb blood gas analysis were measured during six phases of the operation： Pre-CPB (control), CPB-10 min, Rewarm-1 (nasopharyngeal temperature 34 $^{\circ}C$ in the hypothermic group), Rewarm-2 (nasopharyngeal temperature 37 $^{\circ}C$ in the both groups), CPB-off and Post-CPB (skin closure after CPB-off). Postoperaitve neuropsychologic complications were observed in all patients. All variables were compared between the two groups. Result： VMCA at Rewarm-2 was higher in the hypothermic group (153.11$\pm$8.98%) than in the normothermic group (131.18$\pm$6.94%) (p＜0.05). CAVO$_{2}$ (3.47$\pm$0.21 vs 4.28$\pm$0.29 mL/dL, p＜0.05), COE (0.30$\pm$0.02 vs 0.39$\pm$0.02, p＜0.05) and MCMRO$_{2}$ (4.71 $\pm$0.42 vs 5.36$\pm$0.45, p<0.05) at CPB-10 min were lower in the hypothermic group than in the normothermic group. The hypothermic group had higher TEO$_{2}$ than the normothermic group at CPB-10 (1,527.60$\pm$25.84 vs 1,368.74$\pm$20.03, p＜0.05), Rewarm-2 (1,757.50$\pm$32.30 vs 1,478.60$\pm$27.41, p＜0.05) and Post-CPB (1,734.37$\pm$41.45 vs 1,597.68$\pm$27.50, p＜0.05). Internal jugular bulb oxygen tension (40.96$\pm$1.16 vs 34.79$\pm$2.18 mmHg, p＜0.05), saturation (72.63$\pm$2.68 vs 64.76$\pm$2.49 %, p＜0.05) and content (8.08$\pm$0.34 vs 6.78$\pm$0.43 mL/dL, p<0.05) at CPB-10 were higher in the hypothermic group than in the normothermic group. The hypothermic group had less incidence of postoperative neurologic complication (delirium) than the normothermic group (2 vs 4 patients, p＜0.05). Lasting periods of postoperative delirium were shorter in the hypothermic group than in the normothermic group (60 vs 160 hrs, p<0.01). Conclusion: These results indicate that normothermic CPB should not be routinely applied in all cardiac surgery, especially advanced age or the clinical situations that require prolonged operative time. Moderate hypothermic CPB may have beneficial influences relatively on brain metabolism and postoperative neuropsychologic outcomes when compared with normothermic CPB.

• Journal of Yeungnam Medical Science
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• v.3 no.1
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• pp.13-24
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• 1986

마취과 의사는 신경외과수술시 뇌압이 상승되어 있는 환자의 마취를 자주 접하게 된다. 따라서 이러한 환자에서 뇌압의 상승을 억제시키고 뇌압상승 요인들을 제거하며 적당한 뇌혈류량을 유지시킴으로서 이미 손상된 뇌조직을 보호하고 더 이상의 뇌손상을 가하지 않도록 노력해야 한다. 이를 위하여 마취과적 입장에서 고려해 보아야 할 여러 문제점들, 특히 두개강내 역학 즉 뇌용적, 뇌압, 뇌혈류, 뇌산소대사율의 유기적 관계와 마취과에서 쓰여지는 여러약제 및 기타 뇌압과 관계되는 약제 및 요인들에 관하여 기술해 보았다.

• Clinical and Experimental Pediatrics
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• v.46 no.8
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• pp.789-794
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• 2003

Purpose : We intended to evaluate the effect of hypoxia-ischemia on extracellular striatal monoamine metabolism in neonatal rat brains by in vivo microdialysis. Methods : The right common carotid arteries of five or six-day old rats were surgically ligated, and the probes for microdialysis were inserted into the right striatum with stereotaxic instrument. After stabilization for two hours, artificial cerebrospinal fluid was infused via the probe for microdialysis and samples were collected during hypoxia-ischemia and recovery periods at 20 minute intervals. The concentrations of DA(dopamine), DOPAC(3,4-di-hydroxyphenyl acetic acid), HVA(homovanillic acid), NE(norepinephrine), and 5-HIAA(5-hydroxy indole-acetic acid) were measured by HPLC(high performance liquid chromatography) and the changes were analysed. Results : The striatal levels of dopamine metabolites such as DOPAC and HVA, were significantly decreased during hypoxia-ischemia, and increased to their basal level during reoxygenation(P<0.05). Dopamine mostly increased during hypoxia but statistically not significant(P>0.05). DOPAC showed the most remarkable decrease($23.0{\pm}4.2%$, P<0.05), during hypoxia-ischemia and increase to the basal levels during reoxygenation($120.8{\pm}54.9%$, P<0.05), and HVA showed the same pattern of changes as those of DOPAC during hypoxia-ischemia($35.3{\pm}7.6%$ of basal level, P<0.05) and reoxygenation ($105.8{\pm}32.3%$). However, the level of NE did not show significant changes during hypoxia-ischemia and reoxygenation. The levels of 5-HIAA decreased($74.9{\pm}3.1%$) and increased($118.1{\pm}7.8%$) during hypoxia-ischemia and reoxygenation, respectively(P<0.005). Conclusion : Hypoxia-ischemia had a significant influence on the metabolism of striatal monoamine in neonatal rat brains. These findings suggest that monoamine, especially dopamine, and its metabolites could have a significant role in the pathogenesis of hypoxic-ischemic injury of neonatal rat brains.

• Clinical and Experimental Pediatrics
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• v.49 no.3
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• pp.317-325
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• 2006

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 $aa_3$ (Cyt $aa_3$) 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, $PaO_2$, 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($HbO_2$) decreased and hemoglobin(Hb) increased during HI(P<0.05) but returned to base line immediately after RR; 40 min after RR, the $HbO_2$ had decreased significantly compared to NC group(P<0.05). Changes of Cyt $aa_3$ 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.

• Journal of Yeungnam Medical Science
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• v.11 no.1
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• pp.49-54
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• 1994

Postoperative brain damage is one of most serious complications of cardiopulmonary bypass (CPB). To prevent brain damage during CPB, adequate cerebral perfusion for cerebral oxygen demand should be maintained. This study monitored jugular venous oxyhemoglobin saturation ($SjO_2$), which reflects the overall balance of cerebral oxygen supply and demand, intermittently in 10 patients undergoing cardiac surgery. At the initiation of CPB, in spite of a significant decrease in mean arterial pressure, $SjO_2$ did not change, and it was stable during the hypothermic period of CPB. But a significan reduction in $SjO_2$ was observed during the rewarming period, and $SjO_2$ had an inverse linear correlation with esophageal temperature. Furthermore, the percent decrease of $SjO_2$ was related to rewarming speed. Therefore, therapeutic approaches for $SjO_2$ desaturation include slower rewarming, increasing cerebral blood flow, decreasing the cerebral metabolic rate for oxygen, increasing oxygen content, and increasing perfusion flow rate.

• Journal of Life Science
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• v.31 no.12
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• pp.1066-1071
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• 2021

The aim of this study was to examine the metabolic adjustment of lactate dehydrogenase (EC 1.1.1.27, LDH) isozymes to a change in dissolved oxygen (DO) in bluegill (Lepomis macrochirus). After bluegills were adapted to a constant environment in an aquarium, the DO was changed to investigate the activity of LDH isozyme and the relative ratio of subunits A, B, and C for each tissue. When the DO was decreased from 18 ppm to 6 ppm, LDH in skeletal muscle, heart, and brain tissues recovered to the level of control activity within 12, 12, and 6 hr, respectively. LDH activity changed in accordance with a change in DO. The compensation was performed rapidly and is thought to be an important function of LDH in enabling bluegills to adapt to their environment. In bluegill heart, eye, and brain tissues, the relative ratio of subunit A increased and showed a tendency to recover similarly to the subunit ratio of control groups up to 12 hr. It is thought that the anaerobic metabolism using subunit A was increased in the initial stage when DO was changed. In addition, the results revealed that subunit C was more similar to subunit A than subunit B. In bluegills, subunits A and C of LDH seem to be evolutionarily similar. LDH isozymes, mainly containing subunits A and C, are likely responsible for the function of pyruvate reductase, which plays a role in making the bluegill adapt to a hypoxic environment through anaerobic metabolism.