Journal of Chest Surgery

The Korean Society for Thoracic and Cardiovascular Surgery (대한심장혈관흉부외과학회)
권호 표지

Protective Effects of Trimetazidine in a Rabbit Model of Transient Spinal Cord Ischemia

허혈성 척수 손상의 동물실험모델에서 Trimetazidine의 척수 보호효과

  • 장운하 (성균관대학교 의과대학 강북삼성병원 흉부외과) ;
  • 최주원 (성균관대학교 의과대학 강북삼성병원 흉부외과) ;
  • 김미혜 (성균관대학교 의과대학 강북삼성병원 흉부외과) ;
  • 오태윤 (성균관대학교 의과대학 강북삼성병원 흉부외과) ;
  • 한진수 (삼성생명과학연구소 실험동물연구실) ;
  • 김종성 (삼성생명과학연구소 실험동물연구실) ;
  • 이수윤 (이화여자대학교 의과대학 의학과)
  • Published : 2002.04.01
Download PDF
⟨ Previous Next ⟩

Abstract

Paraplegia remains unresolved as the most dreaded operative complication with surgical treatment of descending thoracic and thoracoabdominal aortic diseases. In this study, the neuroprotective effect of trimetazidine that has been used clinically for ischemic heart disease was investigated in a rabbit spinal cord ischemia model. Material and Method: Thirty-three New Zealand white rabbits were randomized as follows: control group undergoing abdominal aortic occlusion but receiving no pharmacologic intervention(Group 1, n= 17); TMZ group(Group 2, n= 16) receiving 3 mg/kg trimetazidine intravenously before the occlusion of the aorta. Ischemia was induced by clamping the abdominal aorta just distal to the left renal artery for 30 minutes. Neurologic status was assessed at 2, 24, and 48 hours after the operation according to the modified Tarlov scale, then the lumbosacral spinal cord was processed for histopathologic examinations 48 hours after the final assessment. Result: The average motor function score was significantly higher in the TMZ group(3.20 $\pm$ 0.77 vs 1.13 $\pm$ 1.25 at 2 hours, 3.50 $\pm$ 0.76 vs 1.45 $\pm$ 1.57 at 24 hours, and 3.91 $\pm$ 0.30 vs 1.86 $\pm$ 1.86 at 48 hours after operation; p value$\leq$0.05). Histologic observations were correlated with the motor scores. Conclusion: The results suggested that trimetazidine reduced spinal cord injury during aortic clamping and that it may have clinical utility for the thoracoabdominal aortic surgery:

배경: 흉부 및 흉복부 대동맥 수술시에 발생하는 척수의 허혈성 손상에 의한 신경학적 합병증은 발병 전의 예측이 어려울 뿐만 아니라 중증의 장애를 남기게 된다. 본 연구에서는 허혈성 심근 질환 치료에 쓰이고 있는 Trimetazidine(이하 TMZ)의 척수의 허혈성 손상에 대한 보호 효과를 동물실험모델에서 실험하였다. 대상 및 방법: 다 자란 New-Zealand White Rabbits 33마리를 대조군(Group 1, N-17)과 실험군(Group 2, N=16)으로 나누어 실험하였다. 수술은 대조군에서는 전신마취 후 정중개복하여 좌측 신동맥 기시 직하부위에서 복부대동맥을 혈관 점자로 30분간 폐쇄하여 척수 허혈을 유발하였으며, 실험군에서는 TMZ 3mg/kg을 대동맥 겸자전 투여하였다. 수술 2시간 후, 24시간 후, 48시간 후에 Modified Talrov scale에 의한 운동능력을 평가하였으며 술 후 48시간에 요천추부 척수를 적출하여 조직검사를 시행하였다. 결과: 대조군과 실험군에서 각각 7 마리(17마리 중 10마리 사망)와 11마리(16마리 중 5마리 사망)가 실험 종료가지 생존하여 척수 조직을 채취하였다. Modified Talrov scale은 대조군과 실험군에서 각각 수술 2시간 후 1.13 $\pm$ 1.25와 3.20 $\pm$ 0.77, 24시간 후 1.45 $\pm$ 1.57와 3.50 $\pm$ 0.76, 48시간 후 1.86 $\pm$ 1.86와 3.91 $\pm$ 0.30이었다(p$\leq$0.05). 척수의 조직학적 검사에서는 신경학적 결손이 큰 대조군(Group 1)의 척수조직에서 허혈성 손상이 더 심하게 일어난 것이 관찰되었다. 결론: TMZ은 동물실험에서 척수의 일과성 허혈성 손상에 대하여 통계적으로 유의한 척수 보호효과를 나타내었다.

Keywords

References

  1. J Thorac Cardiovasc Surg v.33 Reappraisal of adjuncts to avoid ischemia in the treatment of aneurysms of descending thoracic aorta. Crawford ES;Rubio PA.
  2. 제13차 대한흉부외과학회 춘계학술대회 초록집 하행 대동맥류의 수술 최종범
  3. Ann Thorac Surg v.71 Protection of the spinal cord with pentobarbital and hypothermia Shigeru K;Yutaka M;Masaki N. https://doi.org/10.1016/S0003-4975(00)02546-7
  4. Eur J Vasc Endovasc Surg v.22 no.2 An intraaortic solution trial to prevent spinal cord injury in a rabbit model Tetik O;Islamoglu F;Yagdi T. https://doi.org/10.1053/ejvs.2001.1428
  5. Ann Thorac Surg v.42 no.3 Prevention of reperfusion injury of the ischemic spinal cord: use of recombinant superoxide dismutase. Lim KH;Connolly M;Rose D. https://doi.org/10.1016/S0003-4975(10)62735-X
  6. Eur J Cardiothorac Surg v.18 no.2 Ischemic spinal cord injury induced by aortic cross-clamping: prevention by riluzole Lang-Lazdunski L;Heurteaux C;Mignon A. https://doi.org/10.1016/S1010-7940(00)00430-9
  7. J Thorac Cardovasc Surg v.119 no.3 Hypothermic retrograde venous perfusion with adenosine cools the spinal cord and reduces the risk of paraplegia after thoracic aortic clamping Ross SD;Kern JA;Gangemi JJ. https://doi.org/10.1016/S0022-5223(00)70141-3
  8. Resp Exp Med v.200 Protective effects of trimetazidine in transient spinal cord ischemia. Baltalarli A;Coskun E;Ortac R;Onem G;Goksin I;Sirin BH.
  9. Circ Res v.86 no.5 The antianginal drug trimetazidine shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation by inhibiting mitochondrial long-chain 3-ketoacyl coenzyme A thiolase. Kantor PF;Lucien A;Kozak R;Lopaschuk GD. https://doi.org/10.1161/01.RES.86.5.580
  10. Am J Cardiol v.82 no.5A Trimetazidine-induced enhancement of myocardial glucose utilization in normal and ischemic myocardial tissue: an evaluation by position emission tomograhy. Mody FV;Singh BN;Mohiuddin IH. https://doi.org/10.1016/S0002-9149(98)00758-9
  11. Am J Cardiol v.82 no.5A Is the cytoprotective effect of trimetazidine associated with lipid metabolism? Sentex E;Sergiel JP;Lucien A;Grynberg A. https://doi.org/10.1016/S0002-9149(98)00718-8
  12. Am J Cardiol v.76 no.6 Limitation of infarct size by trimetazidine in the rabbit. Noble MI;Belcher PR;Drake-Holland AJ. https://doi.org/10.1016/0002-9149(95)90063-2
  13. J. Cardiovasc Pharmacol v.24 no.1 Effects of trimetazidine on ischemic contracture in isolated perfused rat hearts. Boucher FR;Hearse DJ;Opie LH. https://doi.org/10.1097/00005344-199407000-00008
  14. J Am Coll Cardiol v.409 A201 Ti scintigraphic evidence of Trimetazidine-mediated improvement of coronary micorcirculation in patients with chronic stable angina. Di Girolamo E;Potere F;Sabatini P.
  15. Ann Thorac Surg v.68 Measurement of troponin T to detect cardioprotective effect of trimetazidine during coronary artery bypass grafting. Tunerir B;Colak O;Alatas O;Besogul Y;Kural T;Aslan R. https://doi.org/10.1016/S0003-4975(99)01126-1
  16. J Cardiovasc Surg v.32 Cardioprotective effect of trimetazidine during coronary artery graft surgery. Fabiani JN;Ponzio O;Emerit I.
  17. Carciovasc Drugs Ther v.4 Antiischemic effect of trimetazidine: enzymatic and electric response in a model of in-vitro myocaardial ischemia. Libersa C;Honore E;Adamantidis M;Rouet E;Dupuis B.
  18. Cardiovasc Res v.47 no.4 Changes in intracellular sodium and pH during ischaemia-reperfusion are attenuated by trimetazidine. Comparison between low and zero-flow ischaemia. El Banani H;Bernard M;Baetz D. https://doi.org/10.1016/S0008-6363(00)00136-X
  19. Adv Exp Med Biol v.264 Antioxidant properties of and antitischaemic agent; trimetazidine. Clauser P;Harpey C. https://doi.org/10.1007/978-1-4684-5730-8_39
  20. Arch Int Pharmacodyn Ther v.237 Simultaneous assessment of the effects and trimetazidine on myocardium and coronary vasculature of the dog. Yanagisawa T;Satoh K;Taira N.
  21. Cardiovasc Drug Rev v.6 Trimetazidine, a cellular anti-ischemic agent. Harpey C;Clauser P;Labrid C;Freyria JL;Poirier JP https://doi.org/10.1111/j.1527-3466.1988.tb00381.x
  22. J Nissei Hosp v.9 Effect of trimetazidine granules(Vastare 20mg) in platelet adhesiveness and aggregation in patients with ischemic heart disease. Response to exercise. Higuchi H;Hayachi M;Sano I.
  23. Chest v.109 Spinal cord protection during surgical procedures on descending thoracic and throcoabdominal aorta: review of current techniques. Gharagozloo F;Larson J;Dausmann MJ;Neville RF Jr. https://doi.org/10.1378/chest.109.3.799