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1 J. Exp. Biomed. Sci. 10 (2004) Effect of Hemofiltration in Adults Undergoing Cardiac Operations with Cardiopulmonary Bypass Seok Cheol Choi Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan , Korea The use of hemofiltration has been proposed to reduce excessive body fluid and inflammatory mediators produced during cardiac surgery with cardiopulmonary bypass (CPB) in infants and children. This study was undertaken to evaluate the efficacy of hemofiltration in adult cardiac surgery using CPB. Twenty adult patients scheduled for elective cardiac surgery were randomly assigned to control group without hemofiltration (n=10) or hemofilter group with hemofiltration during CPB (n=10). CBC and serum levels of interleukin-6 (IL-6), D-dimer, endothelin-1 (ET-1), and cortisol were measured at before the initiation and immediately after the termination of CPB (Pre-CPB and End-CPB, respectively). Clinical data were assessed at postoperative period. In hemofilter group hematocrit was significantly higher (30.04±2.63% vs 23.30±2.71%, P=0.0014) whereas total leukocyte count was lower than in control group (7.71 ± /mm 3 vs 16.01± /mm 3, P=0.021) at End-CPB. Increased rate of IL-6 (311.56±97.31% vs ± %, P=0.012) and D-dimer levels (154.55±89.04% vs ±157.64%, P=0.026) at End-CPB were significantly less in hemofilter group than in control group. Postoperative blood transfusion in hemofilter group was low compared with that of control group (741.00±38.07 ml vs 1,137.50± ml, P=0.037). There were no significant differences between two groups in platelet count, ET-1, cortisol, pulmonary index, mechanical ventilation, postoperative blood loss, ICU-stay and hospitalization. Hemofiltration technique applied in the present study provided partly beneficial effect in adult cardiac surgery. Key Words: Cardiac surgery, Cardiopulmonary bypass, Hemofiltration 서 심장수술시적용하는체외순환 (cardiopulmonary bypass) 은수술동안심장과폐의기능을대신하는임상기법으로서현재이를대신할다른방법이없을만큼매우중요한테크닉이다. 그러나체외순환은여러가지유해한효과를유발하여수술후합병증발생의주요원인이되기도한다. 특히그가운데혈액희석과염증반응은체외순환의대표적인유해효과들이다. 혈액희석은교질삼투압의감소를가져와간질액의축적, 조직을통한산소운반능의손상, 여러장기의부종을유도한다. 체외순환시인공심폐기시스템의합성이물질표면에대한환자혈액의접촉은키닌계 (kinins), 혈액 론 * 논문접수 : 2004 년 9 월 9 일수정재접수 : 2004 년 11 월 13 일 교신저자 : 최석철, ( 우 ) , 부산광역시금정구부곡 3 동 9, 부산가톨릭대학교보건과학대학임상병리학과 Tel: , Fax: scchoi@cup.ac.kr 응고인자 XII, 보체계를포함한여러체액성인자들의활성화및염증반응을유도하여관류후증후군 (postperfusion syndrome) 의원인이된다 (Chenoweth DE et al., 1981; Kirklin et al., 1987; Andreasson et al., 1993; Casey LC, 1993; Journois et al., 1994). 최근여러연구자들 (Andreasson et al., 1993; Journois et al., 1994) 은심장수술시헤모필터 (hemofilter) 를이용하여환자의혈액으로부터여분의체액및염증성물질들을제거해줌으로써수술후환자의회복에도움이된다고보고한바있다. 그러나이들연구의대부분은소아환자를대상으로한연구인까닭에성인심장수술환자들에게그대로적용하기위해서는전향적연구가필요하다. 따라서저자는체외순환을동반한성인심장수술에있어헤모필터의사용에따른임상효과를규명하기위해무작위적전향적연구를시행하게되었다. 재료및방법 1. 연구대상 2003년 1월부터 2003년 9월까지부산시소재 P병원에서

2 Table 1. Demographic data in study population Variable Control Group Hemofilter Sample size (number) Gender (male: female) 7:3 6:4 Age (year) 46.44± ±8.71 Body weight (kg) 62.11± ±8.93 BSA (m 2 ) a 1.69± ±0.21 Perfusion rate (L/min/m 2 ) 2.0± ±0.2 NT ( ) b 31.28± ±4.17 ACCT (min) c 78.44± ±12.27 TBT (min) d ± ±20.75 He-Vol (ml) e ± * Data were expressed as the mean ± standard deviation (SD). *, P< (compared with control group). a, body surface area; b, nasopharyngeal temperature during operation; c, aortic crossclamping time; d, total bypass time; e, volume of hemofiltration 체외순환을동반하여판막수술을시행할성인심장병환자 20명을연구대상으로하여연구의목적에따라무작위로대조군 (n=10) 과헤모필터사용군 (n=10) 으로분류하였다. 환자들중수술전비정상적출혈경향이있거나연구에영향을줄만한심각한선행질병이있는경우와재수술환자는연구대상에서제외시켰다. 기본적변수는두군사이에유의한차이가없었다 (Table 1). Fig. 1. Combined diagram of cardiopulmonary bypass system and hemofilter device for cardiac operation. A, arterial blood; AL, arterial line; HB, hemofiltrated blood; V, venous blood; VL, venous line. 2. 체외순환 체외순환에사용된인공심폐기는비박동성 5-head roller pump (Stöckert Co., Germany) 이며, 모든환자들에게동일회사의막형산화기 (Baxter Healthcare Co., USA), 동맥혈필터및순환회로 (GISH Co., USA) 를사용함으로써연구결과의오차발생을최소화하였다. 체외순환회로를환자의심장에연결하기전 heparin (3 mg/kg) 을투여하여혈액응고활성시간이최소 450초이상유지되도록하였다. 인공심폐기충전액으로 Hartman 용액, 15% mannitol (6 ml/kg), sodium bicarbonate (1 meq/kg), calcium chloride (0.6 g), ascorbic acid (1.0 g) 등을사용하여적혈구용적률을 20~25% 정도로유지하였다. 수술시심정지유도및심근보호를위해냉각 HTK (histidine-tryptophan-ketoglutarate, Dr. Franz Kohler Chemie GMBH, Germany) 심정지액을상행대동맥의기시부에주입하거나좌우관상동맥에직접주입하였으며냉각수를이용한심근의국소냉각법을병용하였다. 체외순환시작과함께모든환자들에대해열교환장치를이용하여체온 ( 비인두온도기준 ) 을 29.5~31.8 범위로저하시켰고혈류는 2.0~2.4 l/min/m 2 로유지하였다. 체외순환시동맥혈액을온도비보정의 α-stat 방식으로측정하여 PaCO 2 를 35~40 mmhg 범위로유지하였다. 체외순환종료시모든환자의직장체온이 36 가되게충분히가온하였다. 체외순환종료후 protamine을수술전투여한 heparin 양의 1.5배투여하여혈액활성응고시간이정상치로회복되게하였다. 3. 혈액여과헤모필터를이용한혈액여과는대조군의경우실시하지않았고헤모필터군의경우상품화된 Pan hemofilter (Asahi Medical Co., Tokyo, Japan) 를사용하여실시하였다. 헤모필터는사용전멸균된생리식염수 1500 ml로내부를씻어낸뒤인공심폐기시스템과환자의대동맥사이의동맥혈액순환회로에연결하여서사용하였다 (Fig. 1). 혈액여과는심장수술의주요과정이끝나갈무렵재가온의시작과함께실시하여대동맥교차차단해제직전까지실시하였다. 헤모필터의가동동안약 1000 ml의생리식염수를인공심폐기시스템에첨가하였고전체적으로약 1,897± ml 정도의체액을걸러내었다. 4. 측정변수체외순환시작전과체외순환종료직후의두시기에요

3 골동맥으로부터채취한말초혈액에서다음과같은변수들을측정하였다. 1) 혈액학적변수총백혈구수, 헤마토크리트, 혈소판수를측정하여양군간에비교하였다. 2) Interleukin-6 농도의변화율채취한혈액의혈청을분리하여 interleukin-6 (IL-6) 의체외순환전측정치를 100% 기준으로정하고체외순환종료시의농도를백분율로환산한후양군간에비교하였다. IL-6 농도는 EIA (enzyme immunoassay) 방법에따라상품화된분석시약인 Quantikine HS human IL-6 (R & D System, USA) 를이용하여 Emax precision microplate reader (Molecular Device, USA) 로측정하였다. 3) D-dimer 농도의변화율채취한혈액을 3.2% sodium-citrate 용액이함유된진공튜브에넣고잘혼합한후분리한혈장에서 D-dimer 농도를측정하였는데체외순환전측정치를 100% 기준으로정하고체외순환종료시의농도를백분율로환산한후양군간에비교하였다. D-dimer는상품화된 kit인 Nycocard D-dimer (Axisshield, Norway) 를이용하여 Nycocard reader II (Nycocard, Norway) 분석장비로측정하였다. 4) Endothelin-1 농도의변화율상기의시기에채취한혈액을혈청으로분리하여혈관반응표지자인 endothelin-1 (ET-1) 의농도를측정하여체외순환전측정치를 100% 로하여체외순환종료시의농도를백분율로환산한후양군간에비교하였다. ET-1 농도는상품화된 kit인 Quanti Glo human ET-1 (R & D System, USA) 을이용하여 Luminometer (Digene, USA) 분석장비로측정하였다. 5) Cortisol 농도의변화율상기의시기에채취한혈액을혈청으로분리하여스트레스표지자인 cortisol 농도를측정하여체외순환전측정치를 100% 로하여체외순환종료시의농도를백분율로환산한후양군간에비교하였다. Cortisol 농도는 RIA 방법에따라상품화된 kit인 Coat-A-Count Cortisol (DPC, USA) 을이용하여 Gamma-counter (Packard Co. USA) 분석장비로측정하였다. 6) 폐기능평가양군모두수술후에혈압감시용요골동맥카테터로부터혈액 2 ml를각각채취하여동맥혈액가스분석을하여폐기능지수 (PaO 2 / FiO 2 ) 를구한후실험군간에비교평가하였다. 7) 수술후변수심장수술종료후 24시간및총출혈량, 혈액사용량, 기계호흡보조시간, 중환자실치료기간및재원일수등을조사하여양군간에비교분석하였다. 5. 자료의분석및통계처리각그룹내의연속측정변수들 ( 총백혈구수, 헤마토크리트, 혈소판수, IL-6, D-dimer, ET-1, cortisol) 은 Wilcoxon signedrank test로통계적검정을하였고조사분석한모든변수들의양군간의비교에는 Mann-Whitney test를적용하여그차이를검정하였다. 자료분석은전문통계프로그램인 SAS 를이용하였고 P<0.05일때유의한차이가있는것으로판단하였으며가능한모든자료의값은평균 ± 표준편차로표시하였다. 결 과 1. 혈액학적변수 체외순환종료직후총백혈구수는대조군의경우수술전에비해유의한증가가있었으나헤모필터군의경우유의한 Table 2. Hematological data in two groups Fig. 2. Comparison between control and hemofilter groups in increased rate of serum interleukin-6 (IL-6) concentration. Increased rate of IL-6 at End-CPB was less in hemofilter group than controle group ( * P=0.012 when compared with control roup). Pre- CPB, before CPB; End-CPB, immediately after the termination of CPB. Variable WBC ( 10 3 /mm 3 ) a 7.26± 4.98 Hct (%) b 39.64± 6.30 PLT ( 10 3 /mm 3 ) c ± Pre-CPB Control Hemofilter 6.06± ± ± End-CPB Control Hemofilter 16.01± ± ± ± 1.78 * 30.04± 2.63 ** ± Data were expressed as the mean ± SD. *, P=0.0014; **, P=0.021 (compared with control group). a, total leukocyte count; b, hematocrit; c, platelet count

4 Fig. 3. Comparison between control and hemofilter groups in increased rate of serum D-dimer concentration. Hemofilter group had lower increased rate of D-dimer level compared with controle group at the End-CPB ( * P=0.026 when compared with control group). Table 3. Postoperative clinical data in two groups Variable 상승이없었다. 양군간의비교에서는체외순환종료직후헤모필터군이대조군보다유의하게낮았다. 체외순환종료후헤마토크리트는양군모두체외순환전에비해저하되었고군간의비교에서는헤모필터군이대조군보다유의하게높았다. 혈소판수역시양군모두체외순환종료후유의하게낮았으나군간에는유의한차이가없었다 (Table 2). 2. Interleukin-6 변화율 Control Group Hemofilter PI a ± ± BL (ml) b ± ± T-BL (ml) c ± ± Transfusion (ml) d ± ±38.07 * MV (hr) e 17.43± ±6.73 ICU-stay (hr) 82.71± ±35.82 Hospitalization (day) 20.38± ±5.35 Data were expressed as the mean ± SD. *, P=0.037 (compared with control group). a, pulmonary index (PaO 2 / FiO 2 ); b, volume of blood loss after 24hr postoperatively; c, total volume of postoperative blood loss; d, amount of packed red cell transfusion; e, mechanical ventilation 체외순환종료직후 IL-6의농도는양군모두체외순환전보다유의한증가를보였고군간의비교에서는헤모필터군의증가율이대조군의경우보다유의하게낮았다 (Fig. 2). Fig. 4. Comparison between control and hemofilter groups in increased rate of serum endothelin-1 (ET-1) concentration. There was no significant difference between two groups. 3. D-dimer 변화율 체외순환종료직후 D-dimer 의농도는양군모두체외순환전보다유의한증가를보였고군간의비교에서는헤모필터군의증가율이대조군의경우보다유의하게낮았다 (Fig. 3). 4. Endothelin-1 변화율 체외순환종료직후 ET-1의농도는양군모두체외순환전보다유의한증가를보였으나군간에는유의한차이가없었다 (Fig. 4). 5. Cortisol 변화율 체외순환종료직후 cortisol의농도는양군모두체외순환전보다유의한증가를보였으나군간에는유의한차이가없었다 (Fig. 5). 6. 기타변수 수술종료후폐지수, 24시간및총출혈량, 기계호흡보조시간, 중환자실치료기간, 재원일수등은군간에유의한차이가없었으나혈액사용량은헤모필터군이대조군보다유의하게더적었다 (Table 3). 고 체외순환은 Tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), IL-6, IL-8, 지질및아라키돈산 (arachidonate) 대사물, 혈소판활성인자등과같은염증성매개물질을생성하여전신염증반응을유도한다 (Haeffner-Cavaillon et al., 1989; Kirklin, 찰

5 Fig. 5. Comparison between control and hemofilter groups in increased rate of serum cortisol concentration. There was no significant difference between two groups. 1991; Kawamura et al., 1993; Hattler et al., 1995). 체외순환으로인한전신염증반응은심장수술후상당수의환자들에있어장기기능장애를발생시켜회복을지연시키고이환율및사망률의주요원인이된다 (Kirklin et al., 1987; Kirklin, 1991; Edmunds, 1995). 이러한염증반응의유해효과를완화시키기위해여러방법들이임상에적용되어수술후환자의회복에도움이되고있으며그중헤모필터는부작용이거의없고다목적기능때문에최근들어주목받고있다. 초창기헤모필터는신부전증환자들에있어투석요법의대안으로개발및사용되었으나 1984년 Magilligan 등 (Magilligan et al., 1984) 에의해심장수술에도입되었다. 이들은헤모필터가체외순환시혈액희석을위해투여한다량의충전액을효율적으로제거해주어수술종료시환자의혈액을농축시키고정상체액및전해질균형을회복시켜수술후부종발생률을감소시켜준다고보고하였다. 그러나초창기심장수술에적용된헤모필터에의한전통적혈액여과방법은체외순환실시동안실시해야하므로혈액용적이많은성인환자에게는문제가없으나상대적으로총혈액량이적은소아및어린이환자의경우혈액여과시혈액용적의감소로인한추가적동종혈액의사용이불가피하고헤모필터의충분한가동이어렵다. 특히소아환자들의경우체외순환시스템가동을위해사용하는동종혈액과충전액의양이체중에대비해성인의경우보다상대적으로매우높아소아자신의혈액총량을훨씬능가한다. 따라서체외순환을동반한심장수술후소아환자가성인환자보다더심한부종이발생하게되어유병률및사망률의가장주요한원인이되고있다. 1991년 Naik 등 (Naik et al., 1991a) 에의해개발된변법혈액여과법 (modified ultrafiltration) 은체외순환종료직후환자 의대동맥으로부터혈액을뽑아내어헤모필터를통해수분을어느정도제거한후환자의우심방으로넣어줌으로써전통적체외순환의단점을보완할수있었다. 여러연구자들은심장수술시헤모필터를체외순환시스템에병용함으로써수술후부종발생의감소뿐만아니라염증성매개체의제거, 출혈의감소및기계보조호흡시간의단축, 전신동맥혈압및심박출지수의향상, 폐기능을개선시켜주어유병률및사망률의감소를가져왔다고보고하였다 (Magilligan, 1985; Naik et al., 1991a; Naik et al., 1991b; Andreasson et al., 1993; Journois et al., 1994; Edmunds, 1995; Journois et al., 1996; Draaisma et al., 1997; Koutlas et al., 1997). 그러나이러한연구의대부분이소아및어린아이환자들에대한분석자료이고성인심장수술에대한연구자료는매우극소수인까닭에헤모필터의임상효과를동일선상에서이해하기어렵다. 한편저자의현재연구에서시행된혈액여과법은이미언급한전통적방식과영균형혈액여과법 (Zero-balanced ultrafiltration) 을함께혼용한기법이다. 영균형혈액여과법은혈액여과시링거액이나생리식염수를일정량첨가하면서동량의수분을제거해주는방식으로서혈액의세척효과와함께염증성물질들을제거해주는효과가있다 (Journois et al., 1996). 저자의연구에서체외순환종료시헤모필터군의헤마토크리트수치는대조군에비해유의하게높았고이것은중환자실에있어혈액사용량을감소시키는바람직한계기가되었다. 주지의사실과같이수술후반복적수혈은환자의의료수가를상승시킬뿐만아니라수혈부작용및각종감염의중요한원인이될수있다. 염증성반응의대표적표지자인총백혈구수와 IL-6의변화율은헤모필터군이대조군에비해유의하게낮은수치및낮은증가율을보임으로써헤모필터의유익한효과를확인할수있었다. 이와같은연구결과들은최근발표된 Tassani 등 (Tassani et al., 1999) 과 Grünenfelder 등 (Grünenfelder et al., 2000) 의연구결과와도일치한다. IL-6는분자량이 20~30 kda 정도의단백물질로서전신염증반응의중요한관여체이다. IL-6는관상동맥우회수술을시행한환자들과허혈성심정지를필요로하는심장수술시해당환자들의심장이재관류될때심근에서혈중으로분비되어나온다. 허혈상태의심근은 IL-6의 mrna expression을 up-regulation 시킴으로써 IL-6 생성의주요근원지가된다. IL- 6는각종염증반응뿐만아니라 'stunned myocardium' 의주요원인물질이다 (Nijsten et al., 1987; Finkel et al., 1993). IL-6에의한전신염증반응은말초혈액내백혈구수의증가및활성화를가져오며활성화된백혈구는장기기능장애의원인으로작용한다 (Park et al., 2000). 본연구에서사용한헤모필터는물질제거분자량이약 40~ 60 kda 사이인막 (membrane) 을재질로사용하였기때문에분자량이상대적으로작은심장수술동안생성된 IL-6가일정

6 하게제거된것으로보이며결국염증성물질이제거됨으로써염증반응의완화와함께총백혈구수의상대적감소라는바람직한결과가나타난것으로판단된다. 섬유소의분해산물인 D-dime 증가율역시체외순환종료시헤모필터군이대조군보다유의하게덜하였는데혈중 D-dimer 농도의증가는수술후출혈증가의주요원인이되며, 생성된 D-dimer 가각종염증반응에관여하게된다. 이와같이헤모필터군에있어상대적으로낮은 D-dimer 의농도에관해두가지관점에서의이해적접근이필요하다. 첫째, 헤모필터가대표적염증성사이토카인 (cytokine) 인 IL- 6를상당량제거해줌으로써이차적인섬유소용해계의활성이보다덜일어남으로서 D-dimer의농도가낮았던것으로생각할수있고, 둘째, 이미생성된 D-dimer 역시헤모필터에의해일정부분제거됨으로써대조군보다낮을수있다. 그러나스트레스표지자인 cortisol과혈관반응표지자인 endothelin-l (ET-1) 의변화율은양군간에유의한차이가없었는데, 저자가본연구에서이용한분석방법만으로는이부분에대한해석이어려웠다. 이러한결과가분자량의크기가상이함에따른제거율의차이인지혹은또다른요인에기인한것인지에관해향후더많은연구를통한규명이필요할것이다. 최근 Huang 등 (Huang et al., 2003) 은소아심장수술환자를대상으로실시한연구에서헤모필터를사용하더라도 ET-1은제거되지않았다고보고함으로써저자의연구결과와유사하였다. ET-1은 21 amino acid residues를가진강력한혈관수축성 polypeptide 로서폐고혈압이있는환자의경우혈중농도가증가되며체외순환역시혈관내피손상을일으켜 ET-1 을상승시킨다 (Komai et al., 1993; Tassani et al., 1999). 저자의연구에서조사된수술후임상자료들역시수혈량을제외한나머지변수들인폐지수, 24시간및총출혈량, 기계호흡보조시간, 중환자실치료기간및재원일수등도양군간에유의한차이가없음으로써기존의여러연구결과들과다소상반되는결과를보였다. 이변수들에대한결과의차이가소아와성인환자간의차이인지, 사용한혈액여과방식의차이에기인한것인지는현재로서는알수없으며다만저자의연구에서대상이된환자수가다른연구자들보다상대적으로적었으므로향후더많은환자를대상으로한지속적연구가필요할것으로판단되며헤모필터가어떤종류의사이토카인과물질들을어느정도걸러주는지에대한부분역시또다른연구과제가되어야할것이다. 이상의연구결과를요약해보면성인심장수술시헤모필터의사용은혈액을농축시켜수술후혈액사용량의감소를제공해주고염증성사이토카인을일정량제거시켜염증반응의발생을완화시켜주었다. REFERENCES Andreasson S, Gothberg S, Berggren H, Bengtsson A, Eriksson E, Risberg B. Hemofiltration modifies complement activation after extracorporeal circulation in infants. Ann Thorac Surg : Casey LC. Role of cytokines in the pathogenesis of cardiopulmonary-induced multisystem organ failure. Ann Thorac Surg : Chenoweth DE, Cooper SW, Hugli TE, Stewart RW, Blackstone EH, Kirklin JW. Complement activation during cardiopulmonary bypass: Evidence for generation of C3a and C5a anaphylatoxins. N Engl J Med : Draaisma AM, Hazekamp MG, Frank M. Modified ultrafiltration after cardiopulmonary bypass in pediatric cardiac surgery. Ann Thorac Surg : Edmunds LH. Why cardiopulmonary bypass makes patients sick: Strategies to control the blood synthetic surface interface. Adv Cardiac Surg : Elliott MJ. Ultrafiltration and modified ultrafiltration in pediatric open heart operations. Ann Thorac Surg : Finkel MS, Hoffman RA, Shen L. Interleukin-6 (IL-6) as a mediator of stunned myocardium. Am J Cardiol : Grünenfelder J, Zund G, Schoeberlein A, Maly FE, Schurr U, Guntli S, Fischer K, Turina M. Modified ultrafiltration lowers adhesion molecule and cytokine levels after cardiopulmonary bypass without clinical relevance in adults. Eur J Cardio-thorac Surg : Haeffner-Cavaillon N, Roussellier N, Ponzio O. Induction of interleukin-1 production in patients undergoing cardiopulmonary bypass. J Thorac Cardiovasc Surg : Hattler BG, Zeevi A, Oddis CV, Finkel MS. Cytokine induction during cardiac surgery: Analysis of TNF-alpha expression preand postcardiopulmonary bypass. J Card Surg : Huang H, Yao T, Wang W, Zhu D, Zhang W, Chen H, Fu W. Continuous ultrafiltration attenuates the pulmonary injury that follows open heart surgery with cardiopulmonary bypass. Ann Thorac Surg : Journois D, Israel Biet D, Pouard P. High-volume, zero-balanced hemofiltration to reduce delayed inflammatory response to cardiopulmonary bypass in children. Anesthesiology : Journois D, Pouard P, Greeney WJ, Mauriat P, Vouhe P, Safran D

7 Hemofiltration during cardiopulmonary bypass in pediatric cardiac surgery: Effects on hemostasis, cytokines and complement components. Anesthesiology : Kawamura T, Wakusawa R, Okada K, Inada S. Elevation of cytokines during open-heart surgery with cardiopulmonary bypass: Participation of interleukin-8 and-6 in reperfusion injury. Can J Anaesth : Kirklin JK. Prospects for understanding and eliminating the deleterious effects of cardiopulmonary bypass. Ann Thorac Surg : Kirklin JK, Blackstone EH, Kirklin JW. Cardiopulmonary bypass: studies on its damaging effects. Blood Purif : Komai H, Adatia IT, Elliott MJ, de Leval MR, Hawrth SG. Increased plasma levels of endothelin-1 after cardiopulmonary bypass in patients with pulmonary hypertension and congenital heart disease. J Thorac Cardiovasc Surg : Koutlas TC, Gaynor JW, Nicolson SC. Modified ultrafiltration reduces postoperative morbidity after cavopulmonary connection. Ann Thorac Surg : Park KH, Choi SC, Han IY, Choi KL, Choi KJ, Cho KH. Relationship between interleukin-6 production and inflammatory response during cardiopulmonary bypass. Korean J Thorac Cardiovasc Surg : Magilligan DJ, Oyama C. Ultrafiltration during cardiopulmonary bypass: Laboratory evaluation and initial clinical experience. Ann Thorac Surg : Magilligan DJ. Indications for ultrafiltration in the cardiac surgical patient. J Thorac Cardiovasc Surg : Naik SK, Knight A, Elliott MJ. A prospective randomized study of a modified technique of ultrafiltration during pediatric openheart surgery. Circulation (suppl): III422-III431. Naik SK, Knight A, Elliott M. A successful modification of ultrafiltration for cardiopulmonary bypass in children. Perfusion : Nijsten MW, De Greet ER, Tenduis HJ. Serum levels of interleukin 6 and acute phase responses. Lancet : 921. Tassani P, Richter JA, Eising GP, Barankay A, Braun SL, Haehnel CH, Spaeth P. Influence of combined Zero-Balanced and modified ultrafiltration on the systemic inflammatory response during coronary artery bypass grafting. J Cardiothorac Vasc Anesth : Yoshibayashi M, Nishioka K. Plasma endothelin concentrations in patients with pulmonary hypertension associated with congenital heart defects. Circulation :

황지웅

황지웅 Comparison of Laparoscopy and Exploration in the Distal Pancreatectomy BACKGROUND: To determine the benefits of laparoscopic surgery compared with exploration, the clinical outcomes of open and laparoscopic