J. Exp. Biomed. Sci. 10 (2004) 237 243 A Comparative Study Between On-Pump and Off-Pump Coronary Artery Bypass Grafting on Clinical Outcomes Seong-Min Moon and Seok-Cheol Choi Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, 9 Pugok 3-dong, Keumjeong-gu, Busan 609-757, Korea In recent, many cardiac centers have preferred off-pump coronary artery bypass grafting (CABG) to on-pump CABG to prevent the adverse effects of cardiopulmonary bypass. The present study was performed to prove beneficial effects of off-pump CABG. Sixty adult patients scheduled for elective CABG were randomly assigned to group (n=30) or group (n=30). Arterial blood samples were drawn before and after the operation (Pre-OP and Post-OP, respectively) for measuring CBC, prothrombin time, activated thromboplastine time, blood gas analysis, creatine kinase-mb (CK-MB) level, and lactate dehydrogenase (LDH) level. Perioperative parameters including heparin and protamine usages, complications, blood components usages, blood loss, ventilation and ICU-staying time, and hospitalization were also evaluated. Platelet count at Post-OP was high in group whereas CK-MB and LDH levels were low compared with group. group had significantly lower heparin and protamine usages, lower total leukocyte count, higher hematocrit and hemoglobin levels, less blood loss, lower usages of blood components, shorter ventilation and ICU-staying time, and lower incidence of pleural effusion than group. Other variables did not significantly differ between two groups. These results showed that CABG was a satisfactory technique with less inflammatory reaction, less cardiac damage, less postoperative complications, and less cost. Key Words: Coronary artery bypass grafting,,, CK-MB, LDH 서 전통적인관상동맥우회술은체외순환 (cardiopulmpnary bypass; CPB) 을동반하여대동맥교차차단하에수술이진행된다. 그러나체외순환을동반하는관상동맥우회술은수술시대동맥교차차단과심정지액에의하여불가피하게심근허혈이초래되고수술후혈액성분의기계적손상, 용혈, 부종, 발열, 혈액응고장애, 전신염증반응, 신경장애, 다장기기능부전등과같은관류후증후군 (postperfusion syndrome) 을야기시킨다 (Hope et al., 1981; Brasil et al., 1998; Kim et al., 2000; Kelly et al., 2001; Park et al., 2001). 이러한전통적관상동맥우회수술의부작용을완화시키기위해 1970년대 Ankeney와 Trapp 등에의해체외순환을동반하지않은관상동맥우회술 ( CABG) 이시도되어 1980년대 Benetti와 * 논문접수 : 2004 년 8 월 6 일수정재접수 : 2004 년 9 월 17 일 교신저자 : 최석철, ( 우 ) 609-757, 부산광역시금정구부곡 3 동 9, 부산가톨릭대학교보건과학대학임상병리학과 Tel: 051-510-0564, 0569, Fax: 051-510-0568 e-mail: scchoi@cup.ac.kr 론 Buffalo에의해제한적이나마시행되었으나, 체외순환기법및기구, 심정지액의발전등으로인해이후별로주목을받지못하였다. 그러나 1990년대중반심장보조기구개발및체외순환과심정지액에관한문제점들이보고되면서체외순환비적용관상동맥우회술은다시각광을받기시작하였다 (Kim et al., 2000; Park et al., 2001; Yoo et al., 2002). 체외순환을동반하지않은관상동맥우회술은수술중심근경색빈도, 수술후사망률, 이식혈관의개존율등은전통적인관상동맥우회술과차이가없으나, 산화적손상 (oxidative stress) 과염증반응을감소시킬수있고, 수술후부정맥, 호흡기계및신경계의합병증발생률, 색전증, 감염의위험률등이현저히줄어들고, 수혈의필요성도감소되며, 수술후강심제보조와인공호흡기의존도의감소, 재원시간의단축, 수술비용의감소등도가능하다고보고되고있다 (Brasil et al., 1998; Matata et al., 2000; David et al., 2001; Kelly et al., 2001; Martin et al., 2001; Park et al., 2001; Yoo et al., 2002). 그러나기존연구들의대부분은후향적조사이므로전향적접근을통한연구분석이필요하다. 본연구는체외순환을동반하지않은관상동맥우회술의임상적유용성을규명하기위해수술전후의여러변수들에대해체외순환적용 - 237 -
Table 1. Demographic characteristics in study population Characteristics 관상동맥우회술과전향적으로비교조사하였다. 1. 연구대상 재료및방법 2000년 1월부터 2002년 6월동안관상동맥우회술을시행할성인환자 60명을무작위로체외순환적용관상동맥우회술군 ( 이하체외순환군, n=30) 과체외순환비적용관상동맥우회술군 ( 이하비체외순환군, n=30) 으로분류하였다. 양군공히삼혈관질환 (3 vessels disease) 환자만을대상으로하였고, 수술전신부전환자및응급수술증례, 판막질환이나심근경색후심실중격결손등의다른심장질환을동반한경우는본연구에서제외하였다. 양군사이에체외순환관련부분 ( 체온, 대동맥교차차단시간, 총체외순환시간, 헤파린및프로타민사용량 ) 을제외한나머지변수들은유의한차이가없었다 (Table 1). 2. 체외순환적용관상동맥우회술 Sample size (number) 30 30 Gender (male : female) 17:13 21:9 Age (year) 20.92±10.16 22.69±12.35 Perfusion rate (L/min/m 2 ) 2.0±0.2 0 NT ( ) a) 29.03±1.07 * 34.6±1.85 ACC (min) b) 81.57±36.13 * 0 TBT (min) c) 136.30±46.03 * 0 OPT (hr) d) 5.61±3.94 5.63±2.25 Angina (case) 24 21 MI (case) e) 6 9 Preoperative LVEF (%) f) 60.73±10.30 60.56±12.74 Heparine usage (mg) 258.33±113.64 * 96.83±32.0 Protamine usage (mg) 304.33±136.51 * 78.66±23.57 Data were expressed as mean ± standard deviation (SD). *: P<0.05 (compared with group). a): nasopharyngeal temperature during operation, b): aortic cross-clamping time, c): total bypass time, d):operation time, e): myocardial infarction, f): left ventricular ejection fraction 체외순환군환자들의경우비박동성 Sarns 9000 Roller pump (3 M Healthcare, USA) 인공심폐기, Sarns TCM II Heat exchanger (3 M Healthcare, USA) 열교환기, Univox oxygenator & reservoir (Edwards-Baxter, USA) 막형산화기, 동일회사의동맥혈필터및순환회로 (Dongnam Co., Korea) 를사용한체외순환실시하에관상동맥우회술을시행하였다. 체외순환회로를환자의심장에연결하기전헤파린 (3 mg/kg) 을투여 하여혈액응고활성시간이최소 500초이상유지되도록하였다. 인공심폐기충전액으로 Hartmann 용액, 15% mannitol (6 ml/kg), sodium bicarbonate (40 meq), calcium gluconate (2 g), ascorbic acid (1 g) 등을사용하여적혈구용적률이약 25% 정도유지되게하였다. 체외순환중적혈구용적률이 20% 이하로떨어질경우신선농축적혈구를첨가하였다. 수술시심장정지유도및심근보호를위해냉각혈액심정지액 (4:1) 을상행대동맥의기시부에주입하였으며냉각수를이용한심근의국소냉각법을병용하였다. 체외순환방법은비박동성의중등도저체온법을적용하였고관류는 1.8~2.4 L/ min/m 2 로유지하였다. 체외순환시동맥혈액의산염기평형및가스는온도비보정의 α-stat 방식으로하되 PaCO 2 를약 40 mmhg 범위로유지시켰다. 체외순환중평균동맥혈압은 50~80 mmhg 범위로가능한유지하였고, 만일 50 mmhg 이하일경우 phenylephrine을, 그리고 80 mmhg 이상일경우 sodium-nitroprusside를각각투여하여혈압을정해진범위내로조절하였다. 체외순환종료후체내잔여 heparin 중화를위해 protamine을수술전투여한 heparin 양의 1~1.2배로투여하여혈액활성응고시간이정상치로회복되게하였다. 3. 체외순환비적용관상동맥우회술비체외순환군은전신마취하에체외순환을실시하지않고심장박동상태에서심장안정고정기인 Octopus (Medtronic, Inc. USA, Minneapolis, MN) 나 CTS (Inc. Cupertino, CA, USA), CO 2 blower, 관상동맥내단락장치 (Medtronic, USA) 를사용하여관상동맥우회술을시행하였다. 4. 수술수기양군모두전신마취하에서정중흉골절개를실시하고이식혈관박리후체외순환군의경우환자체중당 300 unit의 heparin을투여하고캐뉼라삽관을하여체외순환하에수술을시행하였고, 비체외순환군의경우에는 heparin을 8,000~10,000 unit를투여하고심근안정고정기를이용하여수술부위의심근을고정시킨후수술을시행하였다. 5. 분석변수 1) 혈액학적변수양군모두수술전과후에혈압감시용요골동맥카테터로부터혈액 3 cc를각각채취하여총백혈구수, 적혈구수, 혈색소농도, 헤마토크리트, 혈소판수를측정하여실험군간에비교평가하였다. 2) Prothrombin time 및 activated partial thromboplastin time 양군모두수술전과후에혈압감시용요골동맥카테터로부터혈액 4 cc를각각채취하여 prothrombin time (PT) 과 - 238 -
Table 2. Preoerative and postoperative hematological aspects in two groups Preoperative Postoperative Preoperative Postoperative Total leukocyte (10 3 /mm 3 ) 7.20±2.07 13.81±3.61 * 6.43±1.53 10.37±2.91 Red blood cell (10 6 / mm 3 ) 4.21±1.36 2.84±0.86 * 4.03±1.47 3.59±1.38 Hemoglobin (g/dl) 12.20±2.40 8.32±1.07 * 12.57±2.39 11.28±2.04 Hematocrit (%) 36.74±5.72 25.15±1.80 * 37.17±4.91 32.89±2.17 Platelet (10 3 /mm 3 ) 214.33±12.05 146.93±11.30 * 207.13±15.84 190.20±10.13 Prothrombin time (sec) 10.79±1.62 12.15±4.50 10.36±1.43 12.08±1.27 aptt (sec) a) 26.52±3.18 42.47±4.50 25.89±2.11 45.35±3.05 Data were expressed as mean ± SD. *: P<0.05 (compared with group). a): activated partial thromboplastin time 5) 수술후혈액제제사용량양군모두수술후혈액제제 ( 전혈, 농축적혈구, 신선냉동혈장, 농축혈소판 ) 사용량을조사하여실험군간에비교평가하였다. 6) 기타변수수술시사용한헤파린및프로타민총량, 수술후출혈량, 기계호흡보조시간, 중환자실치료기간, 재원일수, 수술후 intraaortic balloon pump (IABP) 적용유무, 기타합병증등을조사하여실험군간에비교평가하였다. 6. 자료의분석및통계처리 Fig. 1. Changes of creatine kinase-mb (CK-MB) levels in Onpump and group. The CK-MB level at postoperative period was higher in group than in group (*, P<0.05 when compared with group). activated partial thromboplastin time (aptt) 을각각측정하여실험군간에비교평가하였다. 3) 심근평가효소양군모두수술전과후에혈압감시용요골동맥카테터로부터혈액 2 cc를각각채취하여혈청으로원심분리후심근기능평가효소인 creatine kinase isoenzyme인 CK-MB 농도와 lactate dehydrogenase 농도를측정하여실험군간에비교평가하였다. CK-MB는 Enzyme immuno-inhibition method에의해 CK-MB catridge kit를이용하여 Vitros 950 장비 (Johnson & Johnson, USA) 로측정하였고, LDH는 Enzyme method에의해 LD catridge kit를사용하여상기의동일장비로측정하였다. 4) 폐기능평가양군모두수술후에혈압감시용요골동맥카테터로부터혈액 2 cc를각각채취하여동맥혈액가스분석을하여폐기능을실험군간에비교평가하였다. 양군간모든변수들의비교에는 unpaired t-test와 χ 2 test 를이용하여검정하였다. 자료분석은전문통계프로그램인 SPSS를사용하였고 P<0.05일때유의한차이가있는것으로판단하였으며모든자료의값은평균 ± 표준편차로표시하였다. 결과 1. 혈액학적변수수술후총백혈구수는비체외순환군이체외순환군보다유의하게더낮았고 (10.37±2.91 10 3 /mm 3 vs 13.81±3.60 10 3 /mm 3, P=0.04) 혈소판수, 적혈구수, 혈색소, 헤마토크리트는비체외순환군이체외순환군보다유의하게더높았다 (P<0.05, Table 2). 나머지변수인 PT와 aptt는수술후양군간유의한차이가없었다 (P>0.05, Table 2). 2. 심근효소수술후 CK-MB 농도는비체외순환군이체외순환군보다유의하게덜증가되었고 (28.46±10.38 vs 37.26±12.70 U/L, P=0.04, Fig. 1), LDH 농도역시비체외순환군이상대적으로더낮았다 (533.53±89.04 vs 856.40±114.62 U/L, P=0.03, Fig. 2). - 239 -
Table 4. Volumes of postoperative blood usage and blood loss in two groups Variable Whole blood (pint) 0.03±0.0 * 0.06±0.0 Packed cell (pint) 1.03±0.01 * 0.87±0.0 Fresh frozen plasma (pint) 2.23±0.02 * 0.6±0.0 Platelet (pint) 1.67±0.01 * 0 Blood loss (ml) 857.83±352.70 * 478.01±85.61 Data were expressed as mean ± SD. *: P<0.05 (compared with group) Fig. 2. Changes of lactate dehydrogenase (LDH) levels in Onpump and group. group had significantly higher LDH level than group at postoperative period (*, P<0.05 when compared with group). Table 3. Postoperative blood gas analysis in two groups Variable 3. 동맥혈액가스 수술후동맥혈액가스분석결과는양군간유의한차이가없었다 (P>0.05, Table 3). 4. 수술후혈액제제사용량및출혈량 수술후혈액제제사용량은비체외순환군이체외순환군보다유의하게적었고출혈량역시유의하게더적었다 (P<0.05, Table 4). 5. 기타변수 ph 7.48±0.01 7.41±0.01 pco 2 (mmhg) 36.64±7.52 38.21±5.124 po 2 (mmhg) 105.16±19.97 103.21±17.75 O 2 sat (%) a) 97.45±11.30 97.52±10.08 BE (meq/l) b) 3.24±0.70 0.06±0.0 Bicarbonate (mmol/l) 26.67±7.28 25.49±6.51 c) TCO 2 27.65±5.62 25.49±4.37 Data were expressed as mean ± SD. a): oxygen saturation, b): base excess, c): total CO 2 content 수술시헤파린및프로타민사용량은비체외순환군이체외순환군보다유의하게적었고 (P<0.05, Table 1), 수술후기계호흡보조시간및중환자실치료기간은비체외순환군이체외순환군보다유의하게짧았고흉막삼출사례역시비체외순환군이상대적으로적었다 (P<0.05, Table 5). 재원일수는양군간에유의한차이가없었고, 부정맥, 심막삼출, 발 Variable Table 5. Postoperative outcomes in two group 열, 심각한출혈증, 수술부위감염, 신장기능부전, 다장기기능부전, 협심증, IABP 적용례등은비체외순환군이체외순환군보다적었으나통계적유의함이없었다 (P>0.05, Table 5). 고 심장수술시보편적으로적용하는체외순환은모세혈관투과성의증가로인한간질액의축적, 발열반응, 백혈구수의증가, 출혈경향, 저혈압, 그리고간, 신장, 심장, 폐와같은주요장기의기능장애를포함하여수술초기에생리학적및면역학적변화를초래하는것으로인식되고있으며이러한일련의병태생리학적변화들은체외순환시사용하는수액제제와시스템에기인한다 (Kirklin, 1991). 체외순환시심폐기충전에따른혈액희석으로혈장단백질이희석되어 찰 Ventilation time (hr) 33.77±15.42 * 22.33±10.71 ICU-stay (hr) 106.23±37.06 * 70.48±21.50 Hospitalization (day) 20.13±8.40 20.73±5.24 Arrhythmias (case) 7 6 Pericardial effusion (case) 2 0 Pleural effusion (case) 3 * 0 Fever (case) 1 0 Bleeding-reop (case) a) 2 0 Wound infection (case) 1 0 Renal failure (case) 1 0 Multiorgan failure (case) 1 0 Angina symptom (case) 1 0 IABP insertion (case) b) 1 0 Data were expressed as mean ± SD. *: P<0.05 (compared with group). a): reoperation due to postoperative bleeding, b): intraaortic balloon pump - 240 -
교질삼투압이감소하여간질성부종이발생된다. 또한 histamine, serotonin, lysosomal enzyme 등과같은 vasoactive amine의유리와 kinin의생성으로모세혈관투과성이증가되고혈장내삼투압이감소되며간질내삼투압이증가됨으로써간질성부종이더욱증가하게된다. 또한인공심폐기의작동으로인해혈구성분들이물리적손상을받게되고이로인한용혈이일어나고체외순환회로및산화기와같은인공합성물질의비내피적표면에대한혈액의접촉으로인해혈장단백질, 섬유소원, 혈소판등의흡착이일어나게된다. 이러한비내피적표면에대한혈액의접촉은비특이적인전신염증반응의원인이되는데, 먼저혈장단백질들의활성화가일어나며그결과로 coagulation cascade, complement cascade, kallikrein과같은용해성염증매개체의활성화및유리기산소와같은세포독성물질생성을유도한다 (Westaby, 1987). 게다가체외순환은혈장단백질의변성과지방변성을일으키며, 뇌혈류의감소, 미세물질색전증, 공기색전증으로인한뇌세포장애를유발시키기도한다. 이러한유해한효과들을예방하기위해 heparin-coated circuit, steroid, aprotinin, 혈액여과법등을사용하고있으나근본적인해결책은되지못한다 (Park et al., 2001). 결국이와같은상황들이여러연구그룹들로하여금체외순환을적용하지않는심혈관수술기법에관한활발한실험및연구를유도하게되었다. 체외순환없이심장박동상태하에서시행하는관상동맥우회술은수술수기상의몇몇어려운문제점들을갖고있다. 심장박동으로인해혈관사이의정교한문합이어렵고문합을위하여절개한관상동맥으로부터흘러나오는혈류로인하여수술시야의확보가어려울뿐만아니라심장의뒤쪽에위치한관상동맥분지의문합을하기위하여심장을들어올리면혈압이감소한다 (Fritz et al., 1999; Kim et al., 2000). 그러나, 최근특별히고안된기계적고정기구인 CTS stabilizer와 Octopus tissue stabilizer의개발과 IABP (intraarotic balloon pump: 대동맥내풍선펌프 ) 등의사용등으로이러한문제점들이많이해소되었다. Keith 등 (Keith et al., 1997) 은체외순환비적용관상동맥우회술이체외순환을동반한전통적술식에비해수술후심방세동발생률, 호흡기의존시간, 수혈량, 심장의회복기간, 병원체류시간이현저하게낮았다고보고하였고, Brasil 등 (Brasil et al., 1998) 은체외순환비적용관상동맥우회술이전통적인술식보다 tumor necrosis factor-α 농도, 총백혈구수, 적혈구침강률이더적었다고보고하였다. 이외에도최근의많은연구들은체외순환비적용관상동맥우회술환자군이전통적수술기법인체외순환동반관상동맥우회술환자군보다혈중 C3a 농도, IL-8 레벨, se-selectin 레벨, elastase 레벨, 유리산소기로인한산화성스트레스, 뇌 손상표지단백인 S-100 protein 레벨등이유의하게더낮았다고보고함으로써이새로운수술기법의임상적유용성을지지하였다 (Matata et al., 2000; Wandschneider et al., 2000). 한편본연구자들이전향적으로조사한결과를보면혈액학적변수중체외순환군이비체외순환군보다총백혈구수는유의하게높고혈소판수, 적혈구수, 헤마토크리트, 혈색소농도등은더낮음으로써체외순환으로인한전신염증반응의발생정도와혈구성분의손상정도가더심하였음을알수있었다. 체외순환으로인한혈소판수의급격한저하의요인으로는충전액으로인한혈액희석, 사용한헤파린및프로타민이나헤파린-프로타민복합체 (heparin-protamine complex) 에의한혈소판응집, 용혈된적혈구로부터유리된 ADP 등으로인한혈소판응집, 산화기및인공순환회로에대한혈소판부착, 간이나비장내의혈소판격절 (sequestration) 등을들수있고기능적손상역시동반된다 (Hope et al., 1981; Campbell, 1991). 체외순환군에있어상대적으로심한전신염증반응은수술후환자의회복을어렵게하는합병증발생의원인이될수도있으며, 체외순환실시로인한혈소판수의감소와기능적손상은수술후출혈의주요한원인이되어재수술이나혈액제제사용량의증가를가져올수있고혈액희석으로인한적혈구용적률및혈색소농도의저하는전신산소운반률의감소를동반할수있다. 이러한체외순환의유해한효과가본연구에있어수술후체외순환군이통계적으로유의하게더높은출혈률과더많은혈액제제의사용결과로이어졌다. 심장수술시많은혈액제제의사용은수술후호흡기계감염, 종격동염, 창상감염, 알레르기반응등과같은세균성감염을증가시킬수있으며, 체외순환을적용하지않는관상동맥우회술이전체적인혈액사용량을줄일수있어수혈로인한세균성감염예방에유리하다 (Chelmer et al., 2002). 저자들의연구에서수술후출혈로인해재수술을시행한사례는체외순환군에 2명있었으나비체외순환군은전혀없었다. 비록양군간에통계적으로유의한차이가없었다고는하나의학적관점에있어재수술은환자에게매우위험하고치명적일수도있다. 수술후출혈로인한재수술은환자의유병률및사망률증가의중요한예측인자가되며재수술을받지않은환자에비해수술사망률이약 4.8배나더높다 (Moulton et al., 1996). 본연구에서관상동맥우회술시행동안사용한헤파린및프로타민총량역시체외순환군이비체외순환군보다훨씬높았는데, 이두가지약물은이미전술한부작용외에도헤파린의경우프로타민으로중화시켜도환자에따라서는수술후 rebounding 현상으로심각한출혈의주요원인이될수도있고, 프로타민의경우헤파린과함께복합체를형성 - 241 -
하여고전경로를통한보체계를활성화시킴으로써급작스런저혈압및쇼크의원인이된다 (Kirklin et al., 1986). 따라서헤파린과프로타민의사용량이상대적으로더많은체외순환군이비체외순환군보다이러한잠재적위험요인에처할가능성이훨씬높을것이다. 한편심근효소분석결과를보면수술후 CK-MB와 LDH 농도둘다체외순환군이비체외순환군보다유의하게높음으로써체외순환시비록적절한심근보호기법을사용할지라도관상동맥교차차단에따른허혈성심근손상이필연적으로발생함이시사되었다. 최근관상동맥우회술환자의고령화와기존의다른질환합병가능성을고려해볼때수술중보다심한심근손상은환자회복의중요한변수로작용할수있다. 그외수술후변수들중호흡기의존시간과중환자실치료기간역시체외순환군이비체외순환군보다유의하게길어짐에따라이와관련된의료비용증가가능성과체외순환의손상적효과가시사되었다. 본연구의이러한결과들은체외순환을동반하지않은관상동맥우회술이체외순환동반관상동맥우회술보다의료비용관점에서경제적이고효율적이라는최근의연구보고 (Ascione et al., 1999) 와일치한다. 기타나머지합병증과관련된변수들의경우비체외순환군은거의발생되지않았는데비해체외순환군의경우 1명혹은 2명정도의발생률을보였으나통계적유의함은없었다. 이상의연구결과를요약해볼때체외순환을동반하지않은관상동맥우회술은체외순환으로인한염증반응, 혈구손상, 심근손상, 수술후합병증발생등의문제와의료비용을줄일수있는바람직하고이상적인술식으로생각된다. 그러나비체외순환관상동맥우회술이체외순환관상동맥우회술보다수술후혈관개통률이상대적으로낮다는연구보고 (Gundry et al., 1998) 가있음에따라향후더많은환자를대상으로한보다장기적인추적을통해이식혈관개통률에대한지속적연구조사가필요하리라판단된다. REFERENCES Ascione R, Lloyd CT, Underwood MJ, Lotto AA, Pitsis AA, Angelini GD. Economic outcome of off-pump coronary artery bypass surgery: A prospective randomized study. Ann Thorac Surg. 1999. 68: 2237-2242. Brasil LA, Gomes WJ, Salomão R, Buffolo E. Inflammatory response after myocardial revascularization with or without cardiopulmonary bypass. Ann Thorac Surg. 1998. 66: 56-59. Campbell FW. The contribution of platelet dysfunction to postbypass bleeding. J Cardiothorac Anesth. 1991. 5: 8-12. Chelmer SB, Prato BS, Jr Cox PM, O'Connor GT, Morton JR. Association of bacterial after coronary bypass surgery. Ann Thorac Surg. 2002. 73: 138-142. David AB, Leigh AN, James CS. Coronary artery bypass grafting with cardiopulmonary bypass versus off-pump cardiopulmonary bypass grafting: Does eliminating the pump reduce morbidity and cost? Ann Thorac Surg. 2001. 71: 170-175. Fritz JB, Ali G, Eli RC. Technical aspects of total revascularizatuion in off-pump coronary bypass via sternotomy approach. Ann Thorac Surg. 1999. 67: 1653-1658. Gundry SR, Romono MA, Shattuck OH, Razzouk AJ, Bailey LL. Seven year follow-up of coronary artery bypasses performed with and without cardiopulmonary bypass. J Thorac Cardiovasc Surg. 1998. 115: 1273-1278. Hope AF, Heyns AD, Loter MG. Kinetics and sites of sequestration of indium 111-labeled human platelets during cardiopulmonary bypass. J Thorac Cardiovasc Surg. 1981. 81: 880-886. Keith BA, Robert GM, Robert JR. Minimally invasive versus conventional reoperative coronary artery bypass. Ann Thorac Surg. 1997. 64: 616-622. Kelly CK, Ruth AA, Joseph JS. Coronary artery bypass grafting with and without cardiopulmonary bypass: A comparison analysis. JECT. 2001. 33: 86-90. Kim KB, Lim HG, Huh JH, Ahn H, Ham BM. coronary artery bypass grafting. Kor J Thorac Cardiovasc Surg. 2000. 33: 38-44. Kirklin JK. Prospects for understanding and eliminating the deleterious effects of cardiopulmonary bypass. Ann Thorac Surg. 1991. 51: 529-531. Kirklin JK, Chenoweth DE, Naftel DC. Effects of protamine administration after cardiopulmonary bypass on complement, blood elements, and the hemodynamic state. Ann Thorac Surg. 1986. 41: 193-199. Martin C, Harald B, Juliane K. Complete revascularization in coronary artery bypass grafting with and without cardiopulmonary bypass. Ann Thorac Surg. 2001. 71: 165-169. Matata BM, Sosnowski AW, Galiñanes M. bypass graft operation significantly reduces oxidative stress and inflammation. Ann Thorac Surg. 2000. 69: 785-791. Moulton MJ, Creswell LL, Mackey ME. Reexploration for adverse outcomes after cardiac operations. J Thorac Cardiovasc Surg. 1996. 111: 1037-1046. Park CB, Kwon JB, Park K, Won YS. Coronary artery bypass grafting with cardiopulmonary bypass versus without cardiopulmonary bypass. Kor J Thorac Cardiovasc Surg. 2001. 34: - 242 -
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