Bupivacaine에 의해 억제된 심근수축력에 대한 대사기질의 영향

박승준(Seung-Joon Park),정주호(Joo-Ho Chung),정지창(Jee-Chang Jung),고계창(Kye-Chang Ko) 대한약리학회 1992 대한약리학잡지 Vol.28 No.1

국소마취제인 bupivacaine의 심근억제작용에 관한 기전을 규명하기 위하여, bupivacaine에 의해 수축력이 감소된 흰쥐 적출심장에 대한 각종 대사기질의 영향을 관찰한 바 다음과 같은 결과를 얻었다. 1. Krebs-Ringer glucose medium에 현수한 적출심방의 수축력은 0.01% bupivacaine에 의해 약 50% 감소되었다. 2. Pyruvate, acetate 및 fructose는 bupivacaine 억제심방의 수축력을 증가시켰으나, 정상 Krebs-Ringer medium에서의 수축력에는 현저한 영향이 없었다. 3. Glucose는 bupivacaine 억제심방의 수축력에는 별 영향이 없었으나, 정상 Krebs-Ringer medium에서의 수축력은 증가시켰다. 4. Pyruvate, acetate 및 fructose는 hypertonic medium에 의해 억제된 심방의 수축력에 영향이 없었으나, glucose는 약간의 수축력 증가를 보였다. 5. 각종 대사기질중 pyruvate가 bupivacaine 억제심방의 수축력을 최대로 증가시켰다. 이상의 결과는 bupivacaine이 심근의 glucose 섭취를 억제하거나, 해당과정을 통한 glucose의 이용을 억제하였음을 시사한다. 나아가서, bupivacaine에 의한 대사억제는 심근의 해당과정에서의 phosphofructokinase step이전의 단계에서 작용함을 시사하고 있다. A concentration of 0.01 mM bupivacaine was necessary to maintain approximately 50% depression of contractility of rat atria suspended in a modified Krebs-Ringer bicarbonate glucose medium, pH 7.4 at 30˚C. Sodium pyruvate, sodium acetate, and fructose partially restored the contractility of the bupivacaine-depressed atria. However, 20 mM glucose had no effect on the bupivacaine-depressed atria, although this concentration of glucose markedly increased the contractility of normal atria not to be exposed to bupivacaine. Contractility of normal atria was not significantly influenced by sodium pyruvate, sodium acetate, and fructose. The results suggested that at least part of the negative inotropic action of bupivacaine is the result of inhibition of glucose uptake or utilization in the glycolytic pathway, and further pinpoint the blockade as an early step in the glycolytic sequence prior to the phosphofructokinase step.

Lipid emulsion inhibits vasodilation induced by a toxic dose of bupivacaine by suppressing bupivacaine-induced PKC and CPI-17 dephosphorylation but has no effect on vasodilation induced by a toxic dose of mepivacaine

Cho, Hyunhoo,Ok, Seong Ho,Kwon, Seong Chun,Lee, Soo Hee,Baik, Jiseok,Kang, Sebin,Oh, Jiah,Sohn, Ju-Tae The Korean Pain Society 2016 The Korean Journal of Pain Vol.29 No.4

Background: The goal of this in vitro study was to investigate the effect of lipid emulsion on vasodilation caused by toxic doses of bupivacaine and mepivacaine during contraction induced by a protein kinase C (PKC) activator, phorbol 12,13-dibutyrate (PDBu), in an isolated endothelium-denuded rat aorta. Methods: The effects of lipid emulsion on the dose-response curves induced by bupivacaine or mepivacaine in an isolated aorta precontracted with PDBu were assessed. In addition, the effects of bupivacaine on the increased intracellular calcium concentration ($[Ca^{2+}]_i$) and contraction induced by PDBu were investigated using fura-2 loaded aortic strips. Further, the effects of bupivacaine, the PKC inhibitor GF109203X and lipid emulsion, alone or in combination, on PDBu-induced PKC and phosphorylation-dependent inhibitory protein of myosin phosphatase (CPI-17) phosphorylation in rat aortic vascular smooth muscle cells (VSMCs) was examined by western blotting. Results: Lipid emulsion attenuated the vasodilation induced by bupivacaine, whereas it had no effect on that induced by mepivacaine. Lipid emulsion had no effect on PDBu-induced contraction. The magnitude of bupivacaine-induced vasodilation was higher than that of the bupivacaine-induced decrease in $[Ca^{2+}]_i$. PDBu promoted PKC and CPI-17 phosphorylation in aortic VSMCs. Bupivacaine and GF109203X attenuated PDBu-induced PKC and CPI-17 phosphorylation, whereas lipid emulsion attenuated bupivacaine-mediated inhibition of PDBu-induced PKC and CPI-17 phosphorylation. Conclusions: These results suggest that lipid emulsion attenuates the vasodilation induced by a toxic dose of bupivacaine via inhibition of bupivacaine-induced PKC and CPI-17 dephosphorylation. This lipid emulsion-mediated inhibition of vasodilation may be partly associated with the lipid solubility of local anesthetics.

The Effects of Metabolic Substrates on Contractility of Isolated Rat Atria Depressed with Bupivacaine

박승준,정주호,정지창,고계창,Park, Seung-Joon,Chang, Joo-Ho,Jung, Jee-Chang,Ko, Kye-Chang The Korean Society of Pharmacology 1992 대한약리학잡지 Vol.28 No.1

국소마취제인 bupivacaine의 심근억제작용에 관한 기전을 규명하기 위하여, bupivacaine에 의해 수축력이 감소된 흰쥐 적출심장에 대한 각종 대사기질의 영향을 관찰한 바 다음과 같은 결과를 얻었다. 1. Krebs-Ringer glucose medium에 현수한 적출심방의 수축력은 0.01% bupivacaine에 의해 약 50% 감소되었다. 2. Pyruvate, acetate 및 fructose는 bupivacaine 억제심방의 수축력을 증가시켰으나, 정상 Krebs-Ringer medium에서의 수축력에는 현저한 영향이 없었다. 3. Glucose는 bupivacaine 억제심방의 수축력에는 별 영향이 없었으나, 정상 Krebs-Ringer medium에서의 수축력은 증가시켰다. 4. Pyruvate, acetate 및 fructose는 hypertonic medium에 의해 억제된 심방의 수축력에 영향이 없었으나, glucose는 약간의 수축력 증가를 보였다. 5. 각종 대사기질중 pyruvate가 bupivacaine 억제심방의 수축력을 최대로 증가시켰다. 이상의 결과는 bupivacaine이 심근의 glucose 섭취를 억제하거나, 해당과정을 통한 glucose의 이용을 억제하였음을 시사한다. 나아가서, bupivacaine에 의한 대사억제는 심근의 해당과정에서의 phosphofructokinase step이전의 단계에서 작용함을 시사하고 있다. A concentration of 0.01 mM bupivacaine was necessary to maintain approximately 50% depression of contractility of rat atria suspended in a modified Krebs-Ringer bicarbonate glucose medium, pH 7.4 at $30^{\circ}C$. Sodium pyruvate, sodium acetate, and fructose partially restored the contractility of the bupivacaine-depressed atria. However, 20 mM glucose had no effect on the bupivacaine-depressed atria, although this concentration of glucose markedly increased the contractility of normal atria not to be exposed to bupivacaine. Contractility of normal atria was not significantly influenced by sodium pyruvate, sodium acetate, and fructose. The results suggested that at least part of the negative inotropic action of bupivacaine is the result of inhibition of glucose uptake or utilization in the glycolytic pathway, and further pinpoint the blockade as an early step in the glycolytic sequence prior to the phosphofructokinase step.

Crocin alleviates neurotoxicity induced by bupivacaine in SH-SY5Y cells with inhibition of PI3K/AKT signaling

Lin Lili,Chen Zhen,Li Jun,Peng Jianye,Wang Jian,Feng Mingjun,Liu Tiancheng,Zhang Mengli,Wu Xian,Ai Fen,Shen Caijie 한국유전학회 2024 Genes & Genomics Vol.46 No.1

Background Bupivacaine, a common local anesthetic, can cause neurotoxicity and permanent neurological disorders. Crocin has been widely reported as a potential neuroprotective agent in neural injury models. Objective The aim of this study was to investigate the role and regulatory mechanism of crocin underlying bupivacaine-induced neurotoxicity. Method Human neuroblastoma SH-SY5Y cells were treated with bupivacaine and/or crocin for 24 h, followed by detecting cell viability using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. The effect of crocin or bupivacaine on SH-SY5Y cell proliferation was measured by Ki67 immunofluorescence assay. The levels of apoptosis-related proteins and the markers in the PI3K/Akt signaling pathway were examined using western blot analysis. The activities of caspase 3, catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) were tested using respective commercial assay kits. Flow cytometry analysis was executed for detecting SH-SY5Y cell apoptosis. Result Crocin attenuated bupivacaine-induced neurotoxicity in SH-SY5Y cells. Meanwhile, crocin inhibited SH-SY5Y cell apoptosis induced by bupivacaine via repressing the activity of caspase-3, reducing Bax expression, and elevating Bcl-2 expression. Moreover, crocin mitigated oxidative stress in SH-SY5Y cells by increasing the content of CAT, SOD, GSH-Px and reducing the content of MDA. Additionally, crocin protected against bupivacaine-induced dephosphorylation of Akt and GSK-3β. The protective effects of crocin against bupivacaine-induced neurotoxicity in SH-SY5Y cells were counteracted by the Akt inhibitor. Conclusion These results suggested that crocin may exert a neuroprotective function by promoting cell proliferation and suppressing apoptosis and oxidative stress in SH-SY5Y cells. Thus, crocin might become a promising drug for the treatment of bupivacaine-induced neurotoxicity. Background Bupivacaine, a common local anesthetic, can cause neurotoxicity and permanent neurological disorders. Crocin has been widely reported as a potential neuroprotective agent in neural injury models. Objective The aim of this study was to investigate the role and regulatory mechanism of crocin underlying bupivacaine-induced neurotoxicity. Method Human neuroblastoma SH-SY5Y cells were treated with bupivacaine and/or crocin for 24 h, followed by detecting cell viability using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. The effect of crocin or bupivacaine on SH-SY5Y cell proliferation was measured by Ki67 immunofluorescence assay. The levels of apoptosis-related proteins and the markers in the PI3K/Akt signaling pathway were examined using western blot analysis. The activities of caspase 3, catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) were tested using respective commercial assay kits. Flow cytometry analysis was executed for detecting SH-SY5Y cell apoptosis. Result Crocin attenuated bupivacaine-induced neurotoxicity in SH-SY5Y cells. Meanwhile, crocin inhibited SH-SY5Y cell apoptosis induced by bupivacaine via repressing the activity of caspase-3, reducing Bax expression, and elevating Bcl-2 expression. Moreover, crocin mitigated oxidative stress in SH-SY5Y cells by increasing the content of CAT, SOD, GSH-Px and reducing the content of MDA. Additionally, crocin protected against bupivacaine-induced dephosphorylation of Akt and GSK-3β. The protective effects of crocin against bupivacaine-induced neurotoxicity in SH-SY5Y cells were counteracted by the Akt inhibitor. Conclusion These results suggested that crocin may exert a neuroprotective function by promoting cell proliferation and suppressing apoptosis and oxidative stress in SH-SY5Y cells. Thus, crocin might become a promising drug for the treatment of bupivacaine-induced neurotoxicity.

요추부 내측분지차단술에서 Lidocaine과 Bupivacaine의 비교

문상호,노장호,이송,김지형,신원식 대한척추외과학회 2014 대한척추외과학회지 Vol.21 No.1

Study Design: This is a retrospective clinical study. Objectives: To compare the efficacy of lidocaine and bupivacaine for the ultrasound-guided lumbar medial branch block in chronic lowback pain. Summary of Literature Review: There is no study for comparison of the efficacy between lidocaine and bupivacaine for the medialbranch block. Materials and Methods: From August 2011 to May 2013, 186 patients were assigned 0.5% lidocaine(n=136) or 0.25%bupivacaine(n=45) for the ultrasound-guided lumbar medial branch block. All procedures have been performed by the same operator, and23G, 10 cm needle was placed and drug was injected under ultrasound guide. To target medial branches from lumbar spinal nerve, thegroove at the root of transverse process and the base of superior articular process has been identified on transverse scan. Patients wereevaluated by pre- and post-interventional(1 hour) Visual Analog Scale and analyzed statistically. Results: Reduction of VAS score in bupivacaine group is significantly greater than that in lidocaine group and post-interventional VASscore in bupivacaine group is significantly lower than that in lidocaine group through analysis of covariance test with adjusted preinterventionalVAS score. In multivariate analysis, while age, sex and treatment level were not significant factors, pre-interventionalVAS score and the kind of drug were significant factors. Severe pain before treatment and bupivacaine was indicator of better result. Bupivacaine group reduced pain score in the VAS 2.285 more than lidocaine group with adjustment with other factors. Conclusions: Bupivacaine is more effective than lidocaine in the reduction of pain after ultrasound-guided lumbar medial branch blocksin posterior facet joint syndrome. 연구 계획: 후향적 임상 연구목적: 만성 요통 환자에서 초음파 유도하 내측 분지 차단술을 시행한 환자 중 lidocaine을 사용한 군과 bupivacaine을 사용한 군을 비교하여 어느 약제가우수한가를 분석하고자 하였다. 선행문헌의 요약: 내측 분지 차단술에서 lidocaine과 bupivacaine을 비교한 보고는 없다. 대상 및 방법: 2011년 8월에서 2013년 5월까지 시행한 186명의 내측 분지 차단술 환자들 중 0.5% lidocaine을 주입한 136명과 0.25% bupivacaine을주입한 45명을 비교 분석하였다. 한 명의 의사가 모든 증례를 시술하였으며 초음파 유도하에 23G, 10 cm 주사 바늘을 삽입하고 약제를 주사하였다. 요추 신경의 내측 분지를 목표로 하기 위하여 횡축 영상에서 상 관절 돌기와 횡 돌기의 교차점에 바늘이 놓이도록 하였다. 차단술 전과 시술 후 1시간이경과한 시점에서 Visual Analog Scale (VAS) score를 측정하여 통증 정도를 통계학적으로 비교 분석하였다. 결과: 두 군간의 균질성 분석 상 시술 전 양군의 통증의 VAS에 유의한 차이가 있었기에 이를 보정하고자 ANCOVA test를 시행하여 시술전 VAS의 영향을 교정한 후의 분석에서 bupivacaine군이 유의하게 시술전, 후 VAS의 감소 정도가 많았고 시술 후 VAS도 유의하게 낮았다. 다변량 분석으로 나이, 성별, 처치 level, 시술 전 VAS, 투여 약제 등을 분석하였을 때, 시술전, 후 VAS의 감소 정도는 시술 전 VAS와 투여 약제에 대해서만 의미 있는 결과를 보였다. 즉 시술전 VAS가 높을수록 VAS의 감소 정도가 컸다. 또한 다른 변수의 영향을 보정한 후에도 bupivacaine이 lidocaine보다 2.285만큼 VAS를 유의하게 향상시켰다. 결론 : 후방 관절 증후군에서 초음파 유도하 내측 분지 차단술의 약제 중 bupivacaine이 lidocaine보다 통증 감소면에서 더 우수하였다.

Bupivacaine-induced Vasodilation Is Mediated by Decreased Calcium Sensitization in Isolated Endothelium-denuded Rat Aortas Precontracted with Phenylephrine

Ok, Seong Ho,Bae, Sung Il,Kwon, Seong Chun,Park, Jung Chul,Kim, Woo Chan,Park, Kyeong Eon,Shin, Il Woo,Lee, Heon Keun,Chung, Young Kyun,Choi, Mun Jeoung,Sohn, Ju Tae The Korean Pain Society 2014 The Korean Journal of Pain Vol.27 No.3

Background: A toxic dose of bupivacaine produces vasodilation in isolated aortas. The goal of this in vitro study was to investigate the cellular mechanism associated with bupivacaine-induced vasodilation in isolated endothelium-denuded rat aortas precontracted with phenylephrine. Methods: Isolated endothelium-denuded rat aortas were suspended for isometric tension recordings. The effects of nifedipine, verapamil, iberiotoxin, 4-aminopyridine, barium chloride, and glibenclamide on bupivacaine concentration-response curves were assessed in endothelium-denuded aortas precontracted with phenylephrine. The effect of phenylephrine and KCl used for precontraction on bupivacaine-induced concentration-response curves was assessed. The effects of verapamil on phenylephrine concentration-response curves were assessed. The effects of bupivacaine on the intracellular calcium concentration ($[Ca^{2+}]_i$) and tension in aortas precontracted with phenylephrine were measured simultaneously with the acetoxymethyl ester of a fura-2-loaded aortic strip. Results: Pretreatment with potassium channel inhibitors had no effect on bupivacaine-induced relaxation in the endothelium-denuded aortas precontracted with phenylephrine, whereas verapamil or nifedipine attenuated bupivacaine-induced relaxation. The magnitude of the bupivacaine-induced relaxation was enhanced in the 100mM KCl-induced precontracted aortas compared with the phenylephrine-induced precontracted aortas. Verapamil attenuated the phenylephrine-induced contraction. The magnitude of the bupivacaine-induced relaxation was higher than that of the bupivacaine-induced $[Ca^{2+}]_i$ decrease in the aortas precontracted with phenylephrine. Conclusions: Taken together, these results suggest that toxic-dose bupivacaine-induced vasodilation appears to be mediated by decreased calcium sensitization in endothelium-denuded aortas precontracted with phenylephrine. In addition, potassium channel inhibitors had no effect on bupivacaine-induced relaxation. Toxic-dose bupivacaine-induced vasodilation may be partially associated with the inhibitory effect of voltage-operated calcium channels.

슬관절경수술 후 Morphine, Bupivacaine 그리고 Epinephrine을 함유한 Bupivacaine의 관절내 주사가 술 후 진통에 미치는 효과

정락경,한종인,김종학,김치효,이귀용,이춘희,조연진 梨花女子大學校 醫科大學 醫科學硏究所 1996 EMJ (Ewha medical journal) Vol.19 No.2

목적 : 슬관절경 수술 후 관절강내 morphime bupivacaine epinephrine을 첨가한 bupivacaine을 주사하여 통증 억제 효과 및 수술 소요시간과 종류가 술 후 통증에 미치는 영향을 비교분석하여 효과적으로 임상에 적용하기 위하여 본 연구를 시행하였다. 방법 : 1994년 8월부터 1995년 7월까지 이화대학부속 목동병원에서 계획수술로 슬관절경 수술이 시행된 19~61세 사이의 남녀 40명을 대상으로 하여 전신마취하 슬관절경 수술 후 생리적 식염수 20ml 투여한 대조군, 생리식염수 20ml고 morphine 1mg 혼합투여군, 0.25%bupi-vacaine 20ml 투여군, 0.25% bupivacaine과 200㎍ epinephrine 혼합 투여군으로 분류하여 술 후 1,2,3, 4 및 24시간동안 VAS 를 이용하여 통증을 비교하였다. 결과 : 1) 통계학적인 의의는 없었으나 대조군에 비하여 bu-pivacaine 및 bupivacaine과 epinephrine혼합투여군이 술 후 1시간 이후부터 24시간까지, morphine 투여군은 술 후 3시간 이후부터 통증 억제 효과를 나타내는 경향을 보였다. 2) 수술시간이 60분 미만의 비교적 간단한 수술인 진단적 슬관절경술등 보다 120분 이상의 마모성 관절성형술에서 술 후 통증은 더 심한 경향을 보였다. 결론 : 본 연구에서 전신마취하 슬관절경 수술 후 술 후 통증을 효과적으로 제거하기 위하여 생리식염수, 생리식염수와 morphine 1mg, 0.25% bupivacaine 50mg, epinephrine 200ug고 0.25% bupivacaine을 각각 20ml 관절강내 투여하여 술 후 1,2,3,4 및 24시간 동안 통증이 정도를 비교하여 bupivacaine및 ep-inephrine과 bupivacaine의 혼합용약을 관절강내 주사한 경우 통증억제 효과를 나타내는 경향을 보였고, morphine은 지연된 통증억제 효과를 나타내는 경향을 보였으나, 통계학적으로 의의있는 차이를 발견할 수 없어 앞으로 morphine과 bupivacaine의 관절강내 투여시 용량 및 용적과 통증 관찰 시기를 적절하게 조절하여 더욱 연구해야 할 것으로 사료된다. Objectives : There are controversies about the analgesic effects of intraaarticular morphine and local anethetics bupivacaine. This study sought to compare the effects of saline with mor-phine, bupivacaine with or without epinephrine, administrated intraarticularly upon pos-toperative pan following arthroscopic knee surgery under general anesthesia. Methods : In a double-blined, randommized manner, 40 patients received one of saline(20ml, n=10), morphine(1mg in 20ml NaCl, n=10), bupivacaine(0.25%, 20ml, n=10), bu-pivacaine with epinephrine(0.25%, 20ml, 200ug of epinephrine, n=10) intaarticularly at the completion of surgery. The pain scores by VAS were determined after 1,2,3,4 and 24 hours after intraarticular administration. Results : There were no significant statistical differences between four groups in the pain score. The maximal pain scores were 37.5 in control group, 48.0 in morphine group, 33.6 in bupivacaine group postoperative 1 hour and 32.9 in bupivacaine with epinephrine group pos-toperative 2 hours. The pain scores were decreased as the time went by and were minimin as 21.4 in control group, 17.6 in morphine group, 11.2 in bupivacaine group and 12.3 in bu-pivacaine with epinephrine group 24 hour postoperatively. Conclusion : Though there were no significant statistical significances with those doses, there were tendencies that the bupivacaine group with or without epinephrine had the postoperative analgesic effect rather than control group, and morphine group had a slow onset of analgesic ef-fect. So, we should study to decide the dose or volume of the drugs and appropriate time to evaluate for the anagesic effects after knee arthroscopy further.

Lipid emulsion inhibits vasodilation induced by a toxic dose of bupivacaine by suppressing bupivacaine-induced PKC and CPI-17 dephosphorylation but has no effect on vasodilation induced by a toxic dose of mepivacaine

( Hyunhoo Cho ),( Seong Ho Ok ),( Seong Chun Kwon ),( Soo Hee Lee ),( Jiseok Baik ),( Sebin Kang ),( Jiah Oh ),( Ju-tae Sohn ) 대한통증학회 2016 The Korean Journal of Pain Vol.29 No.4

Background: The goal of this in vitro study was to investigate the effect of lipid emulsion on vasodilation caused by toxic doses of bupivacaine and mepivacaine during contraction induced by a protein kinase C (PKC) activator, phorbol 12,13-dibutyrate (PDBu), in an isolated endothelium-denuded rat aorta. Methods: The effects of lipid emulsion on the dose-response curves induced by bupivacaine or mepivacaine in an isolated aorta precontracted with PDBu were assessed. In addition, the effects of bupivacaine on the increased intracellular calcium concentration ([Ca2+]i) and contraction induced by PDBu were investigated using fura-2 loaded aortic strips. Further, the effects of bupivacaine, the PKC inhibitor GF109203X and lipid emulsion, alone or in combination, on PDBu-induced PKC and phosphorylation-dependent inhibitory protein of myosin phosphatase (CPI-17) phosphorylation in rat aortic vascular smooth muscle cells (VSMCs) was examined by western blotting. Results: Lipid emulsion attenuated the vasodilation induced by bupivacaine, whereas it had no effect on that induced by mepivacaine. Lipid emulsion had no effect on PDBu-induced contraction. The magnitude of bupivacaine-induced vasodilation was higher than that of the bupivacaine-induced decrease in [Ca2+]i. PDBu promoted PKC and CPI-17 phosphorylation in aortic VSMCs. Bupivacaine and GF109203X attenuated PDBu-induced PKC and CPI-17 phosphorylation, whereas lipid emulsion attenuated bupivacaine-mediated inhibition of PDBu-induced PKC and CPI-17 phosphorylation. Conclusions: These results suggest that lipid emulsion attenuates the vasodilation induced by a toxic dose of bupivacaine via inhibition of bupivacaine-induced PKC and CPI-17 dephosphorylation. This lipid emulsion-mediated inhibition of vasodilation may be partly associated with the lipid solubility of local anesthetics. (Korean J Pain 2016; 29: 229-38)

Bupivacaine이 개심장 Purkinje섬유에서 세포내 Na 이온활성도에 미치는 영향

주찬웅,김원호,고재기,이상귀,채수완 대한순환기학회 1997 Korean Circulation Journal Vol.27 No.8

신생 백서 배양 심근세포에 대한 Bupivacaine의 독성 및 회복에 관한 연구

김양일,김양일 대한해부학회 1994 Anatomy & Cell Biology Vol.27 No.4