Histidine-tryptophan-ketoglutarate Versus Blood Cardioplegic Solutions: A Prospective, Myocardial Ultrastructural Study

선천성 심장기형의 수술 후 Histidine-tryptophan-ketoglutarate 심정지액과 혈성 심정지액의 전자현미경적 심근 구조의 비교 관찰

  • Kim, Si-Ho (Department of Cardiothoracic Surgery, College of Medicine, Dong A University) ;
  • Lee, Young-Seok (Department of Pediatric, College of Medicine, Dong A University) ;
  • Woo, Jong-Soo (Department of Cardiothoracic Surgery, College of Medicine, Dong A University) ;
  • Sung, Si-Chan (Department of Cardiothoracic Surgery, College of Medicine, Pusan University) ;
  • Choi, Pil-Jo (Department of Cardiothoracic Surgery, College of Medicine, Dong A University) ;
  • Cho, Gwang-Jo (Department of Cardiothoracic Surgery, College of Medicine, Dong A University) ;
  • Bang, Jung-Heui (Department of Cardiothoracic Surgery, College of Medicine, Dong A University) ;
  • Roh, Mee-Sook (Department of Pathology, College of Medicine, Dong A University)
  • 김시호 (동아대학교 의과대학 흉부외과학교실) ;
  • 이영석 (동아대학교 의과대학 소아과학교실) ;
  • 우종수 (동아대학교 의과대학 흉부외과학교실) ;
  • 성시찬 (부산대학교 의과대학 흉부외과학교실) ;
  • 최필조 (동아대학교 의과대학 흉부외과학교실) ;
  • 조광조 (동아대학교 의과대학 흉부외과학교실) ;
  • 방정희 (동아대학교 의과대학 흉부외과학교실) ;
  • 노미숙 (동아대학교 의과대학 병리학교실)
  • Published : 2007.01.05

Abstract

Background: We performed a prospective clinical study to evaluate the ultrastructural integrity of the myocardium after using Histidine-Tryptophan-Ketoglutarate (HTK) solution in comparison with blood cardioplegic solution during congenital heart surgery. Material and Method: Twenty two patients with acyanotic heart disease, who were scheduled for elective open heart surgery, were randomized into two groups. The HTK Group (n=11) received HTK cardioplegic solution; the blood group (n=11) received conventional blood cardioplegic solution during surgery. The preoperative diagnoses included ventricular septal defect (n=9) and atrial septal defect (n=2) in each group. A small biopsy specimen was taken from the right ventricle's myocardium, and this was processed for ultrastructural examination at the end of 30 minutes of reperfusion. Semiquantitative electron microscopy was carried out 'blindly' in 4 areas per specimen and in 5 test fields per area by 'random systematic sampling' and 'point and intersection counting'. The morphology of the mitochondrial membrane and cristae were then scored. The interstitial edema of the myocardium was also graded. Result: The semiquantitative score of the mitochondrial morphology was $19.65{\pm}4.75$ in the blood group and $25.25{\pm}5.85$ in the HTK group (p=0.03). 6 patients (54.5%) in the blood group and 3 patients (27.3%) in the HTK group were grade 3 or more for the interstitial edema of the myocardium. Conclusion: The ultrastructural integrity was preserved even better with HTK solution than with conventional blood cardioplegic solution.

배경: 선천성 심장기형의 수술적 교정 시, Histidine-Tryptophan-Ketoglutarate (HTK) 심정지액과 혈성심정지액의 심근 보호에 관한 비교를 위해 술 후 심근에 대한 전자현미경적 고찰을 시행하였다. 대상 및 벙법: 개심술을 계획하고 있는 선천성 심기형 환아 22명의 환자를 대상으로 하였고 이들은 무작위로 두 집단으로 나누어 전향적으로 연구를 진행하였다. 22명 중 11명(HTK 집단)은 개심술 시 HTK 심정지액을, 다른 11명(혈성 심정지액 집단)은 혈성 심정지액을 사용하였다. 술 중 재관류 30분 후 우심실에서 작은 조직을 채취하여 전자현미경적 관찰을 시행하였다. 전자현미경에 의한 심근 초미세구조에 대한 평가는 무작위 체계적 표본 추출법에 의한 반정량적 평가법을 사용하였다. 1명의 병리조직학자에 의해 사전정보의 제공 없이 시행되었다. 결과: 미토론드리아의 보존 형태에 대한 반정량적 평가는 혈성 심정지액 집단이 $19.65{\pm}4.75$ 그리고 HTK 집단이 $25.25{\pm}5.85$ (p=0.03)였다. 혈성심정지액 집단 중 6명의(54.5%) 환아에서 그리고 HTK 집단 중 3명(27.3%)에서 3도 이상의 사이질의 부종을 보였다. 결론: 전자현미경적 초미세구조의 보존은 HTK 심정지액이 더 우수한 결과를 보였다. 그러나 임상적 그리고 수술 중의 다양한 요인을 고려한 술 중 심근 보호에 대한 우월성에 대한 비교는 계속적인 관찰과 연구를 요한다.

Keywords

References

  1. Hearse DJ, Bolli R. Reperfusion induced injury: manifestations, mechanism and clinical relevance. Cardiovasc Res 1992; 26:101-8 https://doi.org/10.1093/cvr/26.2.101
  2. Careaga G, Arguero R, Chavez-Negrete A, et al. Control of myocardial reperfusion injury with hypertonic-hyperosmotic solution in isolated rabbit heart. Eur Surg Res 1995;27: 269-76 https://doi.org/10.1159/000129409
  3. Kober IM, Obermayer RP, Brull T, Ehsani N, Schneider B, Spieckermann PG. Comparison of the solutions of Bretschneider, St. Thomas' Hospital and the National Institutes of Health for cardioplegic protection during moderate hypothermic arrest. Eur Surg Res 1998;30:243-51 https://doi.org/10.1159/000008583
  4. Hendry PJ, Labow RS, Keon WJ. A comparison of intracellular solutions for donor heart preservation. J Thorac Cardiovasc Surg 1993;105:667-73
  5. Gebhard MM. Pathophysiologie der globalen Ischamie desHerzens [Pathophysiology of global ischemia of the heart]. Z Kardiol 1987;76(Suppl 4):115-29
  6. Pulis RP, Wu BM, Kneteman NM, Churchill TA. Conservation of phosphorylation state of cardiac phosphofructokinase during in vitro hypothermic hypoxia. Am J Physiol Heart Circ Physiol 2000;279:H2151-8
  7. Stringham JC, Southard JH, Hegge J, Triemstra L, Fields BL, Belzer FO. Limitations of heart preservation by cold storage. Transplantation 1992;53:287-94 https://doi.org/10.1097/00007890-199202010-00007
  8. Flameng W, Dyszkiewicz W, Minten J. Energy state of the myocardium during long-term cold storage and subsequent reperfusion. Eur J Cardiovasc Surg 1988;2:244-55 https://doi.org/10.1016/1010-7940(88)90079-6
  9. Bretschneider HJ. Uberlebenszeit und Weiderbelebungszeit des Herzens bei Normo- und Hypothermie. Verh Dtsch Ges Kreislaufforschung 1964;30:11-34
  10. Bretschneider HJ, Hubner G, Knoll D, Lohr B, Nordbeck H, Spieckermann PG. Myocardial resistance and tolerance to ischemia: physiological and biochemical basis. J Cardiovasc Surg 1975;16:241-60
  11. Hachida M, Ookado A, Nonoyama M, Koyanagi H. Effect of HTK solution for myocardial preservation. 1996;37:269-74
  12. Careaga G, Salazar D, Tellez S, Sanchez O, Borrayo G, Arguero R. Clinical impact of Histidine-Ketoglutarate- Tryptophan (HTK) cardioplegic solution on the perioperative period in open heart surgery patients. Arch Med Res 2001;32:296-9 https://doi.org/10.1016/S0188-4409(01)00296-X
  13. Ku K, Oku H, Alam MS, Saitoh Y, Nosaka S, Nakayama K. Prolonged hypothermic cardiac storage with histidine- tryptophan- ketoglutarate solution. Transplantation 1997;64:971-5 https://doi.org/10.1097/00007890-199710150-00006
  14. Tait GA, Booker PD, Wilson GJ, Coles JG, Steward DJ, MacGregor DC. Effect of multidose cardioplegia and cardioplegic solution buffering on myocardial tissue acidosis. J Thorac Cardiovasc Surg 1982;83:824-9
  15. Sakata J, Morishita K, Ito T. Comparison of clinical outcome between histidine-tryptophan-ketoglutarate solution and cold blood cardioplegic solution in mitral valve replacement. J Card Surg 1998;13:43-7 https://doi.org/10.1111/j.1540-8191.1998.tb01053.x
  16. Buckberg GD. Studies of controlled reperfusion after ischemia, I. When is cardaic muscle damaged irreversibly? J Thorac Cardiovasc Surg 1986;92:483-7
  17. Viten-Johansan J, Johnson WE, Millis SA, Faust KB, Geisinger KR, DeMasi RJ, et al. Reperfusion injury after temporary coronary occlusion. J Thorac Cardiovasc Surg 1988;95:960-8
  18. Schaper J, Hehrlein F, Schlepper M, Thiedemann KU. Ultrastructural alterations during ischemia and reperfusion in human hearts during cardiac surgery. J Mol Cell Cardiol 1977;9:175-89 https://doi.org/10.1016/0022-2828(77)90028-1