한국산 잡견에서 백혈구 제거 충진액이 체외순환 중 위점막 이산화탄소 농도와 IL-8 수준에 미치는 영향

The Effects of Leukocyte Depleted Priming Solution on the Gastric Mucosal $Co_{2}$ Partial Pressure and Serum IL-8 Level during Cardiopulmonary Bypass in Korean Mongrel Dogs

  • 박건 (가톨릭대학교 의과대학 흉부외과학교실) ;
  • 이종호 (가톨릭대학교 의과대학 흉부외과학교실) ;
  • 김진호 (가톨릭대학교 의과대학 흉부외과학교실) ;
  • 진웅 (가톨릭대학교 의과대학 흉부외과학교실) ;
  • 권종범 (가톨릭대학교 의과대학 흉부외과학교실) ;
  • 김치경 (가톨릭대학교 의과대학 흉부외과학교실) ;
  • 왕영필 (가톨릭대학교 의과대학 흉부외과학교실)
  • Park Kuhn (Department of Thoracic and Cardiovascular Surgery, The Catholic University of Korea College of Medicine) ;
  • Lee Jong Ho (Department of Thoracic and Cardiovascular Surgery, The Catholic University of Korea College of Medicine) ;
  • Kim Jin Ho (Department of Thoracic and Cardiovascular Surgery, The Catholic University of Korea College of Medicine) ;
  • Jin Ung (Department of Thoracic and Cardiovascular Surgery, The Catholic University of Korea College of Medicine) ;
  • Kwon Jong Bum (Department of Thoracic and Cardiovascular Surgery, The Catholic University of Korea College of Medicine) ;
  • Kim Chi Kyeong (Department of Thoracic and Cardiovascular Surgery, The Catholic University of Korea College of Medicine) ;
  • Wang Young Pil (Department of Thoracic and Cardiovascular Surgery, The Catholic University of Korea College of Medicine)
  • 발행 : 2005.12.01

초록

배경: 체외순환은 심정지를 필요로 하는 모든 심장 수술에서 정지된 심장의 기능을 대신하여 환자의 말초 장기의 혈액순환을 유지하기 위한 필수적인 과정이다. 그러나 체외순환은 필연적으로 인공도관을 관류하는 특성상 신체의 혈관계를 흐르는 혈류와 달리 혈액손상에 따른 전신성 염증반응을 피할 수 없으며, 이러한 전신성 염증반응과 함께 말초혈관의 미세혈관 순환장애가 체외순환동안에 원발장기의 손상을 초래하는 것으로 생각된다. 저자들은 전신성 염증반응을 일으키는 주된 혈액성분인 백혈구를 제거한 충진액을 사용하여 전신성 염증반응을 줄일 수 있는가를 확인하고, 체외순환도중 위점막의 산도를 측정함으로써 위점막의 미세혈류에 대한 백혈구 제거 충진액의 효과를 확인하기 위하여 실험을 진행하였다. 대상 및 방법: 실험군은 15마리의 한국산 잡견을 충진액의 성분에 따라 비혈액성 충진액군, 백혈구 제거 혈액성 충진액군, 백혈구 비제거 혈액성 충진액군으로 각각 5마리씩 세 군으로 나누었다. 세 군 모두에서 2시간의 체외순환 및 연속된 4시간의 마취유지를 시행하였으며, 체외순환 전과 체외순환 후 1시간, 2시간, 체외순환 종료 후 2시간 4시간에 위점막 이산화탄소 농도와 산도, 동맥혈 이산화탄소 분압 과 호기말 이산화탄소 분압을 측정하고, 염증반응의 지표검사를 위하여 동맥혈을 채혈하였다. 전신성 염증반응의 정도는 채취한 동맥혈에서 ELISA (enzyme linked immunosorbent assay)법을 이용하여 IL-8의 수준을 검사하였다. 결과: 1, 위점막의 이산화탄소 농도는 백혈구 제거 혈액성 충진액군이 백혈구 비제거 혈액성 충진액군과 비혈액성 충진액군에 비하여 유의하게 낮았다(p=0.02, 0.01). 2. 위점막의 산도는 백혈구 제거 혈액성 충진액군과 백혈구 비제거 혈액성 충진액군간에 유의한 차이를 보였다(p=0.01). 3. 전신성 염증반응의 정도를 확인하기 위하여 측정한 IL-8의 수준은 백혈구 제거 혈액성 충진액군과 비혈액성 충진액군이 백혈구 비제거 혈액성 충진액군에 비하여 유의하게 낮았다(p=0.01, 0.01). 결론: 백혈구를 제거한 혈액성 충진액을 사용하는 것이 체외순환중 위점막의 미세순환 장애를 방지하고 전신성 염증반응을 감소시킬 수 있음을 확인하였다.

Background: Cardiopulmonary bypass is an essential process to maintain circulation for saving life during the cardiac surgery, But it is a process in which systemic inflammation was evoked inevitably because of the exposure of blood to foreign surface. The injuries to distal organs during the cardiopulmonary bypass were resulted from systemic inflammation and the disturbances of micro-circulations in the organs. We designed this study to research the effects of leukocyte depletion from pump-oxygenator priming solution on the systemic inflammation, and the micro-circulation of gastric mucosa that is suggested by the gastric mucosal $CO_{2}$ partial pressure and acidity. Material and Method: The dogs were divided into three groups according to the different pump-oxygenator priming solutions; non-hemic crystalloid solution; leukocyte-depleted homologous blood; and non leukocyte-depleted homo-logous blood. Each priming solution group contained five dogs. In all three groups, 2 hours of cardiopulmonary bypass, and 4 consecutive hours of general anesthesia was maintained on the mechanical ventilation. Each dog was evaluated for the gastric mucosal pH, $CO_{2}$ partial Pressure, arterial pH, $CO_{2}$ partial pressure, the exhaled air $CO_{2}$ partial pressure and the level of IL-8 on before the cardiopulmonary bypass, 1 hour after the cardiopulmonary bypass, 2 hours after the cardiopulmonary bypass, 2 hours after the restoration of normal circulation, and 4 hours after the restoration of normal circulation after the cardiopulmonary bypass. The levels of IL-8 were measured with ELISA (enzyme linked immunosorbent assay) technique. Result: 1. There were significant differences of gastric mucosal $CO_{2}$ partial pressure between the leukocyte-depleted homologous blood group and other two groups(vs non leukocyte-depleted homologous blood group; P=0.02, vs non-hemic crystalloid solution group; P=0,01). 2. The gastric mucosal pH of leukocyte-depleted homologous blood group was significantly different from non leukocyte-depleted homologous blood group (p=0.01). 3. The levels of IL-8, which examine the systemic inflammation, showed signi- ficantly better results in leukocyte-depleted homologous blood group and non-hemic crystalloid solution group than non leukocyte-depleted homologous blood group (p=0.01, 0.01). Conclusion: Based upon these results, we concluded that the leukocyte depletion from the pump-oxygenator priming solution has a beneficial effects in reducing systemic inflammation and the preserving of gastric mucosal micro-circulation.

키워드

참고문헌

  1. Kennedy TP, Rao N, Hopkins C, Tolley E, Hoidal J. Reperfusion injury occurs in the lung by free radical mechanisms. Chest 1988;93:149-55 https://doi.org/10.1378/chest.93.1.149
  2. Weiss SJ. Tissue destruction by neutrophils. N Engl J Med 1989;320:365-76 https://doi.org/10.1056/NEJM198902093200606
  3. Kim WK, Rho JR. 심폐바이패스의 이론과 실제. 서울: 고려의학, 1996. 359-73
  4. Steinberg BM, Grossi EA, Schwartz DS, et al. Heparin bonding of bypass circuits reduces cytokine release during cardiopulmonary bypass. Ann Thorac Surg 1995;60:525-9 https://doi.org/10.1016/0003-4975(95)00482-Z
  5. Hill GE, Whitten CW, Landers DF. The influence of cardiopulmonary bypass on cytokines and cell-cell communication. J Cardiothorac Vasc Anesth 1997;11:367-75 https://doi.org/10.1016/S1053-0770(97)90107-5
  6. Bolling KS, Halldorsson A, Allen BS, et al. Prevention of the hypoxic reoxygenation injury with the use of a leukocyte- depleting filter. J Thorac Cardiovasc Surg 1997;113:1081-9 https://doi.org/10.1016/S0022-5223(97)70295-2
  7. Gott JP, Cooper WA, Schmidt FE Jr, et al. Modifying risk for extracoporeal circulation: trial of four antiinflammatory strategies. Ann Thorac Surg 1998;66:747-54 https://doi.org/10.1016/S0003-4975(98)00695-X
  8. Bando K, Pillai R, Cameron DE, et al. Leukocyte depletion ameliorates free radical-mediated lung injury after cardiopulmonary bypass. J Thorac Cardiovasc Surg 1990;99:873-7
  9. Schmid Ra, Yamashita M, Audo K, Tauaka Y, Cooper Jb, Patterson GA. Lidocaine reduces reperfusion injury and neutrophil migration in canine lung allograft. Ann Thorac Surg 1996;61:949-55 https://doi.org/10.1016/0003-4975(95)01182-X
  10. Bonser RS, Fragomeni LS, Edwards BJ. Allopurinol and deferoxamine improve canine lung preservation. Transplant Proc 1990;22:557-8
  11. Morioka K, Muraoka R, Chiba Y, et al. Leukocyte and platelet depletion with a blood cell separator: effects on lung injury after cardiac surgery with cardiopulmonary bypass. J Thorac Cardiovasc Surg 1996;111:45-54 https://doi.org/10.1016/S0022-5223(96)70400-2
  12. Sawa Y, Taniguchi K, Kadoba K, et al. Leukocyte depletion attenuates reperfusion injury in patients with left ventricular hypertrophy. Circulation 1996;93:1640-6 https://doi.org/10.1161/01.CIR.93.9.1640
  13. Button LN, DeWolf WC, Newburger PE. The effects of irradiation on blood components. Transfusion 1981;21:419-26 https://doi.org/10.1046/j.1537-2995.1981.21481275998.x
  14. Buescher Es, Holland PV, Gallin JI. Radiation induced defective assessed by nitroblue tetrazolium (NBT) reduction (abstract). Clin Res 1983;31:309-14
  15. Schmidt FE Jr, MacDonald MJ, Murphy CO, Brown WM 3rd, Gott JP, Guyton RA. Leukocyte depletion of blood cardioplegia attenuates reperfusion injury. Ann Thorac Surg 1996;62:1691-6 https://doi.org/10.1016/S0003-4975(96)00736-9
  16. Baldwin ML, Jefferies LC. Irradiation of Blood Components. American Association of Blood Banks, Bethesda, Maryland. 1992;51-75