• Journal of Chest Surgery
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• 제31권9호
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• pp.845-854
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• 1998

Background: S-2-(3 aminoprophlamino) ethylphosphorothioic acid(WR-2721) is one of the radical scavenging thiols. We tested its protective effects in the reperfused heart. Material and Method: The experimental setup was the constant pressure Langendorffs perfusion system. We investigated the radical scavenging properties of this compound in isolated rat hearts which were exposed to 20 minutes ischemia and 20 minutes reperfusion. Four experimental groups were used:group I, control, Amifostine 50 mg(1 mL) peritoneal injection 30 minutes before ischemia(group II), Amifostine 10 mg(0.2 mL) injection during ischemia through coronary artery(group III),and Amifostine 50 mg(1 mL) peritoneal injection 2 hrs before ischemia(group IV). The experimental parameters were the levels of latate, CK-MB, and adenosine deaminase(ADA) in frozen myocardium, the quantity of coronary flow,and left ventricular developed pressure, and it's dp/dt. Statistical analysis was performed using repeated measured analysis of variance and student t-test. Result: The coronary flow of group II and IV were less than group I and III at equilibrium state but recovery of coronary flow at reperfusion state of group II, III, and IV were more increased compared with group I. The change of systolic left ventricular devoloping pressure of group II and IV were less than control group at equilibrium state, which seemed to be the influence of the pharmacological hypotensive effect of amifostine. But it was higher compared with group I at reperfusion state. The lactic acid contents of group II were less than control group in frozen myocardium.(Group I was 0.20 0.29 mM/g vs Group II, which was 0.10 0.11 mM/g). The quantity of CK-MB in myocardial tissue was highest in group IV (P=0.026 I: 120.0 97.8 U/L vs IV: 242.2 79.15 U/L). The adenosine deaminase contents in the coronary flow and frozen myocardium were not significantly different among each group. Conclusion: Amifostine seemed to have significant cardioprotective effect during ischemia and reperfusion injuries of myocardium.

• Journal of Chest Surgery
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• 제32권11호
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• pp.971-977
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• 1999

Background: Immunologic and inflammatory responses of cardiopulmonary bypass(CPB) influence postoperative mortality and morbidity with multiple organ injury. It has been reported that ischemia/reperfusion induced-myocardial injury during CPB is causative of release of inflammatory cytokines such as interleukin-6(IL-6) and tumor necrosis factor-$\alpha$ (TNF-$\alpha$). The purpose of this study was to detect the time course of the activated cytokine and troponin-T(TnT), and to examine the correlation between such parameters during CPB. Material and Method: The serial samples were collected from arterial blood via radial arterial catheter in 23 patients who are underwent open heart surgery (OHS) with CPB, the IL-6, TNF-$\alpha$ and TnT were checked. Result: \circled1 IL-6, TNF$\alpha$- and TnT concentration increased significantly during CPB with a peaking level of CPB-off (p 0.05). \circled2 IL-6 had highly positive correlation with aortic cross clamping time and total bypass time(r=0.80, 0.78; p 0.05, respectively). \circled3 There was no correlation among IL-6, TNF-$\alpha$ and TnT. Conclusion: In conclusion, these data showed that elevated production of serum IL-6 during CPB was attributable to ischemia/reperfusion induced-myocardial damage. IL-6 will become a new and sensitive biological marker in assessment of myocardial damage during OHS with CPB. However, further studies will be needed to apply IL-6 in more patient population.

• The Korean Journal of Physiology and Pharmacology
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• 제3권6호
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• pp.579-586
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• 1999

Complement-mediated neutrophil activation has been hypothesized to be an important mechanism of reperfusion injury. It has been proposed that C1 esterase inhibitor (C1 INH) may prevent the complement- dependent activation of polymorphonuclear leukocytes (PMNs) that occurs within postischemic myocardium. Therefore, The effect of C1 INH was examined in neutrophil dependent isolated perfused rat heart model of ischemia (I) (20 min) and reperfusion (R) (45 min). Administration of C1 INH (5 mg/Kg) to I/R hearts in the presence of PMNs $(100{\times}10^6)$ and homologous plasma improved coronary flow and preserved cardiac contractile function (p＜0.001) in comparison to those I/R hearts receiving only vehicle. In addition, C1 INH significantly (p＜0.001) reduced PMN accumulation in the ischemic myocardium as evidenced by an attenuation in myeloperoxidase activity. These findings demonstrate the C1 INH is a potent and effective cardioprotective agent inhibits leukocyte-endothelial interaction and preserves cardiac contractile function and coronary perfusion following myocardial ischemia and reperfusion.

• Journal of Chest Surgery
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• 제20권2호
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• pp.230-240
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• 1987

Cardioplegia and myocardial protection were performed under cardiopulmonary bypass during open-heart surgery with the use of cold St. Thomas Hospital cardioplegic solution [4=C] for the coronary artery perfusion and normal saline solution [4- C] for the topical cardiac cooling. To maintain the state of myocardial protection, coronary artery reperfusion was carried out using St. Thomas Hospital cardioplegic solution at the interval of 30 minutes. A total number of patients studied were 57 cases, including 37 cases of correction for congenital cardiac anomalies and 20 cases for acquired heart valvular diseases. Cardiopulmonary bypass time during the surgery was observed to be average of 87.89*47.55 hours, aortic cross-clamping time to be average of 76.68~44.27 hours raging from 30 to 191 minutes. In order to evaluate the effects of myocardial protection in the surgery, serum enzyme levels were determined. To observe the relationship between aortic cross-clamping time and myocardial protection effects, patients studied were divided into the following 3 groups. I group: aortic cross-clamping time, 60 minutes, II group: aortic cross-clamping time, 90 minutes, III group: aortic cross-clamping time, over 91 minutes. 1. Changes in serum enzyme levels in postoperative period. [1] SCOT; The postoperative value [increased over 200 units] for ischemic myocardial injury during operation was observed in 11 cases [19.3% of the total] of the total patients studied, of which 4 cases [13.3%] in I group, 1 case [10.0%] in II group, and 6 cases [35.3%] in III group. [2] LDH; The positive value [increased over 900 units] for ischemic myocardial injury during operation was observed in 9 cases [15.7% of the total] of the total patients studied, of which 2 cases [6.6%] in I group, 1 case [10.0%] in II group, and 6 cases [35.3%] in III group. [3] CPK; The positive value [increased over 800 units] for ischemic myocardial injury during operation was observed in 10 cases [17. 5% of the total] of the total patients studied, including 4 cases [13. 3%] in I group, 1 case [10.0%] in II group, and 5 cases [29.4%] in III group. 2. The myocardial protection method used in the present study was demonstrated to be effective for the myocardial protection in the surgery with aortic cross-clamping time of up to 90 minutes. A few ischemic myocardial injury were observed in the surgery with aortic cross-clamping time over 91 minutes, but no significant cardiac dysfunction was noted. The surgery with aortic cross-clamping time of up to 191 minutes did not appear to give rise any significant interference with postoperative recovery.

• Journal of Chest Surgery
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• 제22권2호
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• pp.225-233
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• 1989

Cardioplegia and myocardial protection were performed under cardiopulmonary bypass during open heart surgery with the use of St. Thomas Hospital cardioplegic solution [4 [C] for the coronary artery perfusion and normal saline solution [4[ c] for the topical cardiac cooling. To maintain the state of myocardial protection, coronary artery reperfusion was carried out using St. Thomas Hospital cardioplegic solution at the interval of 30 minutes. A total number of patients studied were 57 cases, including 37 cases of correction for congenital anomalies and 20 cases for acquired heart diseases. Cardiopulmonary bypass time during the surgery was observed to be average of 87.89*47.55 hours, aortic cross-clamping time [ACCT] to be average of 76.68*44.27 hours raging from 30 to 191 minutes. In order to evaluate the effects of myocardial protection in the surgery, serum enzyme levels were determined. To observe the relationship between ACCT and myocardial protection effects, patients studied were divided into the following 3 groups. I group: ACCT 60 minutes, II group: ACCT 90 minutes, III group: ACCT over 91 minutes [1] SGOT; The positive value [increased over 200 units] for ischemic myocardial injury during operation was observed in 11 cases [19.3% of the total] of the total patients studied, of which 4 cases [13.3%] in I group, 1 case [10.0%] in II group, and 6 cases [35.3%] in III group. [2] LDH; The positive value [increased over 900 units] for ischemic myocardial injury during operation was observed in 9 cases [15.7% of the total] of the total patients studied, of which 2 cases [6.6%] in I group, 1 case [10.0%] in II group and 6 cases [35.3%] in III group. [3] CPK; The positive value [increased over 800 units] for ischemic myocardial injury during operation was observed in 10 cases [17.5% of the total] of the total patients studied, including 4 cases [13.3%] in I group, 1 case [10.0%] in II group, and 5 cases [29.4%] in III group [4] The myocardial protection method used in the present study was demonstrated to be effective for the myocardial protection in the surgery with ACCT of up to 90 minutes. A few ischemic myocardial injury were observed in the surgery with ACCT over 91 minutes, but no significant cardiac dysfunction was noted. The surgery with ACCT of up to 191 minutes did not appear to give rise any significant interference with postoperative recovery.

• Journal of Chest Surgery
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• 제29권10호
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• pp.1076-1080
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• 1996

허혈후 재관류시 일산화질소의 전구체인 L-arginin에 심근기능에 미치는 영향은 각 연구의 조건에 따라 일정하지 않다. 저자들은 L-arginine의 농도에 의한 심근보호효과의 차이를 알아보고자 본 연구를 시행하였다. 란겐돌프 관류장치하의 흰쥐 적출심장에 37.5$^{\circ}C$에서 30분의 허혈과 30분의 재관류를 실시하면서 재관류시 관류액에 L-arginine을 첨가하여 농도를 1, 2, 3, 4 mm/L로 하였고 대 조군에는 L-arginine을 첨가하지 않았다. 허혈기 직전과 재관류 30분에 좌심실 수축기능(좌심실 발생압, 좌심실압 최대 순간 증가율), 이완기능(좌심실압 최대 순간 감소율)과 관상관류량을 측정하였다. L-arginine 농도가 1mm/L, 2 mm/L인 실험군은 좌심실 발생압, 좌심실압 최대 순간증가율, 좌심실압 최대 순간감소율 및 관상관류량의 회복률이 대조군에 비해 통계적 유의성은 없었으나 우수한 경향을 보였다. 그러나 L-arginine의 농도가 증가함에 따라 회복률은 감소하여 4 mM/L농도의 실험군은 대조군보다 유의하게 낮은 회복률을 보였다(p(0.05). 이러한 연구결과를 통해 심근허혈후 재관류시 심근기능 및 관상관류량 회복을 향상시키기 위해서는 L-arginine을 2mM/ 이하의 농도로 투여 해야 하며 향후 그 이상의 높은 농도에서 나타난 회복 저하에 관한 연구가 필요할 것으로 생각된다.

• The Korean Journal of Physiology and Pharmacology
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• 제25권3호
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• pp.239-249
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• 2021

The present study explored the therapeutic potential of hydrogen sulfide (H2S) in restoring aging-induced loss of cardioprotective effect of remote ischemic preconditioning (RIPC) along with the involvement of signaling pathways. The left hind limb was subjected to four short cycles of ischemia and reperfusion (IR) in young and aged male rats to induce RIPC. The hearts were subjected to IR injury on the Langendorff apparatus after 24 h of RIPC. The measurement of lactate dehydrogenase, creatine kinase and cardiac troponin served to assess the myocardial injury. The levels of H2S, cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), nuclear factor erythroid 2-related factor 2 (Nrf2), and hypoxia-inducible factor (HIF-1α) were also measured. There was a decrease in cardioprotection in RIPC-subjected old rats in comparison to young rats along with a reduction in the myocardial levels of H2S, CBS, CSE, HIF-1α, and nuclear: cytoplasmic Nrf2 ratio. Supplementation with sodium hydrogen sulfide (NaHS, an H2S donor) and l-cysteine (H2S precursor) restored the cardioprotective actions of RIPC in old hearts. It increased the levels of H2S, HIF-1α, and Nrf2 ratio without affecting CBS and CSE. YC-1 (HIF-1α antagonist) abolished the effects of NaHS and l-cysteine in RIPC-subjected old rats by decreasing the Nrf2 ratio and HIF-1α levels, without altering H2S. The late phase of cardioprotection of RIPC involves an increase in the activity of H2S biosynthetic enzymes, which increases the levels of H2S to upregulate HIF-1α and Nrf2. H2S has the potential to restore aging-induced loss of cardioprotective effects of RIPC by upregulating HIF-1α/Nrf2 signaling.

• Journal of Chest Surgery
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• 제29권8호
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• pp.807-815
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• 1996

허혈전처치(ischemic preconditioniiIE)의 허혈심장 보호효과와 그 기전을 규명하기 위한 일환으로 citric oxide(HO)가 허혈전처치의 심보호 효과에 미치는 영향을 검토하였다. 흰쥐 적출심장의 Langendorrr관류표본에서 실험적인 허할(30분)-재관류(30분) 손상을 유도하였고, 허혈전처치는 재관류손상 유도 전에 5분 허혈 - 5분 재관류를 3회 반복하여 시행하였다. 허혈심근 손상의 지표로 심수축기능 세질효소 유출 및 미세형태학적 변화를, 그리고 HO 합성 억제제인 L-HAME 를 투여하여 허혈전처치와 비전처치 허혈-재관류 심장들에서 손상의 정도를 비교하였다. 그 결과 허혈- 재관류 심장에서 심기능의 저하및 세포질 유출이 현저하게 증가하였고 전자현미경상의 미세구조에서도 세포내 소기관 및 myofibril의 파괴가 관찰되 어 심근손상이 심함을 알 수 있었다. 허 혈-재관류에 의한 심 장손상은 허혈전처치를 시행한 허혈-재관류 심장에서는 현격하게 감소돼 심회복률이 77%로 증가하였 고 세포질유출도 현저하게 감소되었으며 미세소견에서도 세포구조가 비교적 잘 보존되었다. 허혈전처 치에 의한 심보호 효과에 NO가 관여하는지를 관찰하기 위하여 NO합성 억제제인 L-NAME를 투여하 여 허혈전처치를 시행하였다. 결과 L-UAME투여로 허혈전처치에 의하여 회복된 심기능 및 LDH유출 감소에 아무런 영향을 주지 않았고 허혈전처치에 의하여 비교적 잘 보존된 미세구조 역시 영향을 받지 않았다. 이상의 결과들로부터 허혈전처치는 세포수준에서 허혈심근의 재관류손상을 방지하며, NO합성의 증가가 횐쥐 적출 심장에서 허혈전처치에 의한 허혈심장 보호효과에 크게 기여하지 않을 것으로 사료되었다.

• Journal of Chest Surgery
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• 제31권8호
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• pp.739-748
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• 1998

연구배경: 재관류 없이 허혈 심근세포의 기능이나 형태학적 변화를 원래의 상태로 회복시킬 수 없음은 주 지의 사실이나 재관류가 반드시 유익하지만은 않다는 실험결과들이 있으므로 국소적으로 일과성 허혈을 유도하여 심근세포에서 일어나는 형태학적 변화를 관찰하고 재관류가 허혈심근에 미치는 영향을 알아보고자 하였다. 재료 및 방법: 생후 12개월 내외의 홀슈타인종 소를 사용하여 정맥 마취하에서 흉부를 열고 왼쪽 관상동맥 의 전하방 가지를 20분 동안 결찰하여 국소허혈을 유도하고 결찰을 풀어 재관류를 유도하였다. 위험부위의 심근조직 을 재관류 직후, 재관류후 1, 2, 3, 6, 12시간 및 재관류 12시간후 1시간동안 보조호흡과 수액공급만을 한 후 각각 생검하여 통상적인 방법으로 처리하여 투과전자현미경으로 관찰하였다. 결과: 20분 동안의 국소허혈로 심근세포는 경도에서 중등도에 이르는 미세구조적 변화들이 나타났는데 특히 세포막하, 핵, 사립체, 심근원섬유 등의 소기관에서 많은 변화들이 관찰되었다. 그러나 재관류를 시작하여 1시간이 지나면 허혈심근세포에서는 회복을 시사하는 소견들이 나타나기 시작하였으며 미세혈관 내에서 혈전형성이나 내강의 협착 등이 관찰되었으나 재관류가 계속됨에 따라 심근세포의 미세구조적 변화들은 서서히 회복되어 가는 양상을 나 타내었다. 그러나 시간이 경과함에 따라 심내막하 심근세포의 일부에서는 재관류 손상으로 추측되는 미세구조적 변 화들이 관찰되었다. 결론: 이상의 결과로 미루어 미세혈관은 허혈에 대한 저항력이 심근세포보다 강하며 허혈 심근세포는 재관류 없이는 회복될 수 없고, 회복에는 비교적 장시간이 요구되며, 따라서 혈관폐쇄로 인한 허혈시 혈관성형술이나 혈전 용해를 촉진하는 물질을 이용한 치료는 타당성이 있는 것으로 생각되나 재관류 유발성 세포손상에 대한 주의가 요망 된다.

• Journal of Chest Surgery
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• 제29권8호
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• pp.850-860
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• 1996

활성산소는 동물실험에서 심근 재관류손상의 중요기전으로 알려져 있으나 실제 임상상황에서의 역할은 아직도 논란이 많다. 본 연구에서는 냉혈 심마비 액을 사용한 심근보호법을 이용하여 관상동맥우회술 을 시행받는 환자들을 대상으로 하여 심근허혈후 재관류시 활성산소에 의한 심근의 손상 정도 및 활성 산소 방어효소계의 변동과 그 기전을 규명하고자 하였다. 관상동맥우회술을 받는 환자(n=10)를 대상으로 하여 관상정 맥동 환류혈액 에서 상행대동맥 차단 전과 재관류 20분 후에 lactate dehydrogenase(LDH), creatinG phosphokinase MB 분획(CK-MB)과 malondialdehyde(MDA)의 농도를 측정하였으며 또한 같은 시각에 심근의 superoxide dismutase(SOD), catalase, glutathione peroxidase(GSHPX), glutathione reductase(GSSGRd) 그BT고 glucose 6- phosphate dehydrogenase(GGPDH)의 활성도를 측정하였다 관상정 맥동혈에서의 LDH(268 $\pm$40.3 to 448 $\pm$ 84.9 ml plasma)와 CK-MB(4.50$\pm$ 2.33 to 27.1$\pm$13.5 Ulml plasma)의 활성도 그리고 MDA(5.87$\pm$2.02 to 10.5$\pm$2.23 nmol/ml plsma)의 양은 상행대동맥 차단 전에 비하여 재관류 후에 현저히 증가하였으 \ulcorner심근의 SOD(13.5$\pm$4.04 to 20.7$\pm$8.56 mg protein), GSHPX(279 $\pm$)7.2 to 325$\pm$51.4 mU/mg protein) 그리고 GSSCRd(97.2$\pm$15.9 to 122 $\pm$25.1 m2/mg protein)의 활성도도 재관류후에 현저히 증가하였다 반면 심근의 catalase와GSPDH의 활성도는의미있는 변화가 없었다 한편 SOD에 대한 Western blot결과 Cu, Zn-SOD의 양이 현저하게 증가되었음을 관찰 하였다. 이상의 결과들로 관상동맥우회술시 상행대동맥차단에 따른 심근허혈후 재관류에 의하여 활성산소에 의한 산화성 심근손상이 일어나지만 동시에 활성산소 방어효소계의 활성 또한 증가됨으로써 심근손상 의 정도가 약화되었을 가능성을 추정할 수 있으며 이러한 활성산소 방어효소의 활성증가는효소단백의 광합성 증가에 의한 것으로 여겨진다.