Effect of Global Ischemic Preconditioning After Cardioplegic Arrest -Langendorff Isolated Heart Study-

단기간의 심근허혈이 심근보호에 미치는 영향 -적출 쥐 심장의 연구-

  • Cheon, Young-Jin (Department of Thoracic and Cardiovascular Surgery, Medical College, Korea University) ;
  • Lee, In-Sung (Department of Thoracic and Cardiovascular Surgery, Medical College, Korea University) ;
  • Kim, Yeon-Soo (Department of Thoracic and Cardiovascular Surgery, Medical College, Korea University) ;
  • Choi, Young-Ho (Department of Thoracic and Cardiovascular Surgery, Medical College, Korea University) ;
  • Kim, Kwang-Taik (Department of Thoracic and Cardiovascular Surgery, Medical College, Korea University) ;
  • Kim, Hyoung-Mook (Department of Thoracic and Cardiovascular Surgery, Medical College, Korea University) ;
  • Kim, Hark-Jei (Department of Thoracic and Cardiovascular Surgery, Medical College, Korea University) ;
  • Lee, Gun (Department of Thoracic and Cardiovascular Surgery, Heart Center, Pundang CHA General Hospital, Collage of Medicine, Pochon CHA University)
  • 전영진 (고려대학교 의과대학 흉부외과학교실) ;
  • 이인성 (고려대학교 의과대학 흉부외과학교실) ;
  • 김연수 (고려대학교 의과대학 흉부외과학교실) ;
  • 최영호 (고려대학교 의과대학 흉부외과학교실) ;
  • 김광택 (고려대학교 의과대학 흉부외과학교실) ;
  • 김형묵 (고려대학교 의과대학 흉부외과학교실) ;
  • 김학제 (고려대학교 의과대학 흉부외과학교실) ;
  • 이건 (포천중문의과대학 분당차병원 흉부외과)
  • Published : 1998.02.01

Abstract

Ischemic preconditioning is known to have protective effect on myocardial function at prolonged ischemic insult but the mechanism of the effect is not clearly known. The effect of the preconditioning on the global ischemia using cardioplegic solution is not well known. To evaluate the effect of global myocardial preconditioning on the functional recovery after cardioplegic arrest and two hours of hypothermic storage, we used the isolated rat heart and two hours cardioplegic arrest time at $0^{\circ}C$. In the experimental group(n=10), after baseline functional data was obtained, ischemic preconditioning was induced with 1 min of global normothermic ischemia for three times before the arrest period. In the control group(n=10), hearts underwent no ischemic precondi- tioning. After 2 hrs of cardioplegic arrest and storage in the $0^{\circ}C$ cardioplegic solution reperfusion was done and hemodynamic data were collected at post-reperfusion 20 min. Heart with ischemic preconditioning showed improved functional recovery at post reperfusion 20 min in peak developed pressure and dP/dT. In percent change of the peak pressure, preconditioning group showed 93.20$\pm$15.7% recovery rate compared to baseline data, and control group showed 67.3$\pm$15.6% recovery rate. In percent change of the dP/dT, control group showed 54.7$\pm$18.2% recovery rate and preconditioning group showed 78.1$\pm$15.1% recovery rate. Percent changes in heart rate and coronary flow showed no significant difference between two groups and there was no significant differences in amount of cardioplegic delivery between groups. Our data suggest ischemic preconditioning may have protective effect on recovery state after cardioplegic arrest and 2 hr ischemic storage of isolated rat heart and its mechanism is not related to the amount of the cardioplegic delivery amount.

짧은 기간의 허혈은 뒤에 오는 장시간의 허혈 및 재관류시에 심근의 손상방지에 효과가 있는 것으로 보고되고 있으나 그 기전에 대해서는 논란이 많다. 본 연구에서는 심근에 단기간의 허혈조건을 부여한 후 심근보호액을 이용하여 심정지를 유도하였고 다시 재관류하였을 때 심근 기능의 회복에 미치는 영향을 연구하기 위해 적출 쥐 심장모델을 이용하여 2 시간의 저장기를 이용하여 재관류시의 기능을 비교하였다. 10 마리의 실험군에서는 심근보호액을 이용한 심정지전에 1 분간의 전체 허혈기를 가지고 5 분간의 재관류를 3 번 반복하는 방법으로 허혈조건부여를 하였으며 대조군에서는 위와 같은 조건부여 없이 2 시간의 심근보호액을 이용한 심정지 및 저장기를 가졌다. 2 시간의 저장기를 $0^{\circ}C$의 심근보호액에서 가진 후 재관류를 하여 두 군간의 회복시의 기능을 비교하였다. 재관류 20 분후의 회복기 기능의 비교에서 허혈 조건부여를 한 실험군에서 대조군에 비하여 좌심실 발생압 및 좌 심실압 순간 변화율에서 우수한 회복율을 보였다. 심정지전의 수치를 100으로 본 경우의 재관류시의 좌심실 발생압의 회복율에서 허혈 조건부여를 준 실험군에서는 93.20$\pm$15.7%의 회복율을 보인 반면 대조군에서는 67.3$\pm$15.6%의 회복율을 보여 차이가 있었다. 좌심실압 순간 변화율의 회복율에서 대조군은 54.7$\pm$18.2%의 회복율을 보인 반면 실험군에서는 78.1$\pm$15.1% 의 회복율을 보였다. 심박동수 및 관동맥 관류량에서는 양 군에서 통계적으로 유의한 차이를 발견하지 못하였으며 같은 압력으로 관류한 심근보호액의 관류량에서도 유의한 차이를 보이지 않았다. 이상의 결과 허혈 조건부여는 적출 쥐 심장에서 심근보호액을 이용한 심정지 및 2 시간의 저장 후 재관류시의 심근 기능 회복에 재관류시 심근기능 회복에 도움이 된다고 생각되며 이는 심근보호액의 관류량 및 관류저항과는 다른 기전에 의한 것으로 생각된다.

Keywords

References

  1. Circulation v.82 Mechanism of myocardial stunning Roberto Bolli R
  2. J Clin Invest v.56 Regional myocardial functional and electrophysiological alterations after brief coronary artery occlusion in conscious dogs Heyndrickx GR;Millard RW;McRithie RJ;Maroco PR;Vatner SF
  3. Cardiovasc Res v.18 Repetitive episodes of brief ischemia do not produce a cumulative depletion of high energy phosphate compounds Swain JL;Sabina RL;Hines JJ;Greenfield JC;Holms EW
  4. Am J Physiol v.261 Four brief periods of myocardial ischemia cause no cumulative ATP loss or necrosis Reimer KA;Murry CE;Yamasawa I;Hill ML;Jennings RB
  5. Circulation v.74 Preconditioning with ischemia : a delay of lethal cell injury in ischemic myocardium Murry CE;Jeinning RB;Reimer KA
  6. Am Heart J v.123 The transient nature of the effect of ischemic preconditioning on myocardial ion- faect size and ventricular arrythmia Yuwei L;Whittaker P;Kliner RA
  7. 대흉외지 v.27 적출 쥐 심장에서 허혈성 전조건화가 심정지후 좌심실 기능에 미치는 영향 조대윤
  8. Ann Thorac Surg v.58 Ischemic preconditioning improves preservation wiht crystalloid cardioplegia Illes RW;Wright JK;Mcbride KI;Yang CJ;Tristan A
  9. Circ Res v.38 Mitochondrial structure and function in acute myocardial ischemic injury Jennings RB;GAnote CE
  10. Circulation v.84 Protection against infacrction afforded by preconditioning is mediated by Al adenosine receptors in the rabbit heart Liu GS;Thornton J;Van Winkle DM;Stanley AWH;Olsson RA;Downey JM
  11. Circulation v.82 Myocardial protection with preconditioning Li GC;Vasquez JA;Gallager KP;Lucchesi BR
  12. Circ Res v.66 Ischemic preconditioning reduces invarct size in swine myocardium Schott RJ;Rohmann S;Braun ER;Schaper W
  13. Circ Res v.68 Effect of preconditioning ischemia on reperfusion arrythmias afteroronary artrery occlusion and reperfusion in thee rat Hegar JM;HAle DJ;Kloner RA
  14. Heart Circ physiol v.32 Role of endothelium derived nitric oxide in myocardial reactive hypermia Yamabe H;Okumura K;Ishizaka H;Tsuchiya T;Yasue H
  15. 대흉외지 v.29 NO억제제가 허혈전처치의 심장보호효과에 미치는 영향 유호진;조은용;장인엽;전제열;최철희;임동윤
  16. J Mol Cardiol v.24 no.SUP.Ⅰ Ischemic preconditioning is not prevented by inhibition of endothelial derived nitric oxide Patel VC;Woolfson RG;Singh KJ;Yellon DM
  17. J Thorac Cardiovasc Surg v.109 Endothelium dependent contraction of canine coronary artery is enhanced by crystalloid cardioplegic solution Lin PJ;Chang CH;Yao PC;Liu HP;Hsieh HC
  18. Circ Res v.66 Control of coronary vascular tone by nitric oxide Kelm M;Schrader J
  19. Circulation v.89 Ischemic preconditioning protects against coronary endothelial dys-function induced by ischemia and reperfusion Richard V;Kaeffer N;Tron C;Thuillez C
  20. Ann Thorac Surg v.61 Hyperkalemia alters endothelium dependent relaxation through non nitric oxide and noncyclooxygenase pathway : A mechanism for coronary dys-function due to cardioplegia He GW;Yang CQ
  21. Circ Res v.70 Role of nitric oxide in reactive hyperemia of the guinea pig heart Kostic MM;Scharader J
  22. J Mol Cardiol v.23 Energy metabolism in preconditioned and controled myocardium : Effect of total ischemia Jennings RB;Murry CE;Reimer KA
  23. Circ Res v.63 Heat shock response is associated with enhanced post ischemic ventricular recovery Currie RW;Karmazyn M;Kloc M;Mailer K
  24. Circulation v.82 no.Ⅲ Whole body heat stress protects the isolated perfused rabbit heart Yellon DM;Pasini E;Ferrari R;Downey JM;Latchman DS
  25. Circulation v.91 Mechanism of ischemic preconditioning in rat myocardium-Role of adenosine, cellular energy state, and mitochondrial FIF2-ATPase Vuorinen K;Ylitalo K;Peuhkurinen K;Raatikainen P;Ala-Rami A;Hassinen IE
  26. Transplantation v.60 Ischemic preconditioning improves cardiac functional recovery following preservation with Unuversity of Wisconsin solution Saitoh Y;Gu K;Kin S(et al.)