Effect of Pyruvate and Aspartate Enriched University of Wisconsin Solution on Myocardial Protection

피루브산염과 아스파라진산염을 첨가한 위스콘신대학 용액의 심근보호 효과

  • 이정렬 (서울대학교 의과대학, 흉부외과학교실, 서울대학교병원 임상의학연구소) ;
  • 김준석 (서울위생병원 흉부외과) ;
  • 한재진 (이화여자대학교 의과대학, 흉부외과학교실) ;
  • 강문철 (서울대학교 의과대학, 흉부외과학교실, 서울대학교병원 임상의학연구소)
  • Published : 2002.01.01

Abstract

Background: Ischemia-reperfusion myocardial injury is an important factor to determine the early and the late mortality of transplanted patients. Recently, modulation of the cytosolic NADH/NAD+ ratio by Pyruvate and aspartate was tested to Protect the heart from ischemia-reperfusion injury. Material and Method: We added pyruvate and aspartate to the University of Wisconsin solution, and evaluated their effect on myocardial protection. We used 16 piglet(age 1 to 3 days) hearts. Eight hearts were arrested with and stored in the University of Wisconsin solution(UW solution) for 24 hours(control group), and the other eight hearts were arrested with and stored in the modified UW solution added pyruvate(3mmol/L) and aspartate(2 mmol/L)(test group). All hearts underwent modified reperfusion with blood cardioplegic solution followed by conversion to a left-sided working model with perfusion from a support pig. And then, we measured stroke work index(SWI), high-energy phosphate stores, and myocardial water content of the hearts. SWI was calculated at left ventricular end-diastolic pressures of 3, 6, 9, and 12 mmHg after 60 and 120 minutes reperfusion, respectively, Result: At 60 minutes and 120 minutes after reperfusion, SWI was higher in the test group than in the control group significantly. The levels of AMP, ADP, ATP of the test group were also higher. But, the creatine phosphate level and myocardial water content were similar in the two groups. Conclusion: From these results, we could Prove that pyruvate and aspartate enhance cardiac contractility and high-energy phosphate stores after ischemia.

배경: 심장이식에 있어서 허혈-재관류 손상은 이식심장의 기능회복이나 장기생존을 좌우하는 중요한 요소이다. 본 연구에서는 세포질내의 NADH/NAD$^{+}$ 비율의 조절에 관여하는 피루브산염과 아스파라진산염을 현재 일반적으로 흔히 쓰이고 있는 장기 보존액인 위스콘신대학 용액에 첨가하여 심근을 보호하고 재관류 후의 심장 보존능의 효과를 증명하고자 하였다. 대상 및 방법: 생후 3일 이내의 신생돈의 심장을 4$^{\circ}C$ 위스콘신대학 용액(대조군, n=8)과 피루브산염과 아스파라진산염을 첨가한 위스콘신대학 용액(실험군, n=8)으로 심정지를 유도하여 적출하고 4$^{\circ}C$ 동일한 용액에서 24시간 동안 허혈상태로 보존한 후, 성돈을 교차순환 재관류혈 공급원으로 사용하여 좌심단순작업성 관류모델(left-sided working heart model)로 재관류 시킨 다음, 관류심장에서 일정한 시간 간격으로 박출작업계수(stroke work index)를 측정하였고, 관류가 끝난 후, 고 에너지 인산함유량(high-energy Phosphate stores), 심근의 수분 함유량(myocardial water content)을 측정하여 두 군을 비교하였다. 결과: 재관류가 시작되고 60분과 120분이 경과된 후에 좌심실 확장기말 압력(LVEDP)이 3, 6, 9, 및 12mmHg일 때 각각 박출작업계수를 측정하였는데, 60분이 경과된 후에 측정한 박출작업계수는 실험군에서 통계적으로 유의하게 높았고 [n=8, p<0.05, 대조군(16.3 $\pm$8.3$\times$1,000 erg/g) vs. 실험군(33.1 $\pm$ 15.1$\times$1,000 erg/g)], 120분이 경과된 후에도 실험군에서 통계적으로 유의하게 높게 나타났다 [n=8, p<0.05, 대조군(15.8$\pm$8.0$\times$1,000 erg/g) vs. 실험군(35.1$\pm$16.3$\times$l,000 erg/g)〕고 에너지 인산 중, AMP, ADP, 및 ATP의 함유량은 실험군에서 높게 측정되었다 [n=8, p<0.05, AMP -대조군(30.8$\pm$8.7 micromo1/g myocardium) vs. 실험군(53.1$\pm$11.1),ADP -대조군(52.6$\pm$7.3) vs. 실험군(91.3$\pm$20.9), ATP -대조군(67.5$\pm$23.8) vs. 실험군(156.5$\pm$45.8)]. 그러나, creatine phosphate 함유량 [n=8, p>0.05, 대조군(546.6$\pm$197.0 micromol/g myocardium) vs. 실험군(595.5$\pm$179.6) 과 심근 수분 함유량 [n=8, p>0.05, 대조군(87.2$\pm$5.5%) vs. 실험군(82.4$\pm$10.1)] 은 두 군간에 유의한 차이가 없었다. 결론: 이상의 결과는 피루브산염 와 아스파라진산염이 첨가된 위스콘신대학 용액이 위스콘신대학 용액만을 사용한 경우보다, 박출작업계수와 심근에너지 보존 측면에서 평가하기로는 심근보호 기능이 더 우수하다는 것을 나타내고 있다. 그리고, 대사과정에서 NADH/NAD$^{+}$의 대사와 관련이 없는 creatine phosphate의 보존에는 차이가 없다는 결과는 피루브산염과 아스파라진산염이 세포질내의 NADH/NAD$^{+}$의 조절에 관여하여 심근을 보호하리라는 가설을 가능하게 한다.

Keywords

References

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