• Journal of Chest Surgery
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• 제33권2호
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• pp.117-124
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• 2000

Background: Nucleoside transport inhibitor(NTI) Keeps AMP, ADP, ATP levels high in myocytes by inhibiting adenosine cataboilsm so that it may preserve the myocardial contractability during ischemia In this study we investigated the effects of cyclic AMP phosphodiesterase inhibor(C-AMP PDSI) and S-P-nitrobenzyl-6 -thioniosine(NBT; a sort of NIT) on myocadial preservation and changes of constituent enzyme. Material and method: Twenty-six isolated rabbit hearts were perfused with Krebs-Henseleit buffer solution for 20 minutes arrested for 20 minutes and ten reperfused for 30 minutes. The following four groups were prepared and hemodynamic changes coronary effluent lactate dehydrogenase (LDH) a-hydroxybutylic accid(a-HBD) levels and myocardial LDH creatine kinase-MB (CK-MB) adenosine deaminase(ADA) a-HBD levels and myocardial LDH creatine kinase-MB (CK-MB) adenosine deaminase(ADA) a-HBD levels were analysed before and after cardiac arest ; Group I(control) ; the heart was only perfused with K-H ; Group II ; the heart was perfused with K-H including C-AMP PDSI(Amrinone 25mg/L); Group III ; the heart was perfused with K-H including NBT(4.19mg/L) ; Group IV ; the heart was perfused with K-H including C-AMP PDSI + NBT. Result : Left venticular developed pressure(LVDP) at 10 minutes of the equilibrium was significantly higher in group III(72.1$\pm$5.3 mmHg p<0.01) and group III(72$\pm$5.6 mmHg P<0.025) as compared with group I (40.8$\pm$4.7mmHg) and LVDP at 20 minutes of the reperfusion was significantly higher in group II(74$\pm$5.3mmHg p<0.01) and group III(72$\pm$5.6mmHg p<0.025) as compared with group I (44.2$\pm$4.6mmHg). Percentage recovery of LVDP at the reperfusion was the highest in group II(123.3%) Percentage recovery of coronary flow at the equilibrium reperfusion were higher in group II(310%, 270%) group III(230%, 290%) group IV(310%, 280%) as compared with group I (100%) respectively. Myocadial LDH level was significant lower in group IV(33495$\pm$1802 IU/gm p<0.04) as compared with group I(48767$\pm$1421 IU/gm) Myocadial CK-MB level was significant higher in group II(74820$\pm$1421 IU/gm) compared with group I (45450$\pm$1737 IU/gm) Myocadial ADA level was significant higher group IV(1215$\pm$8 IU/gm p<0.05) compared with group I(125$\pm$15 IU/gm) but there was no significant difference between group I and group II ,III, IV in changes of coronary effluent LDH, a-HBD levels. Conclusion: C-AMP PDSI solely appears to have a better effect on myocardial preservation after ischemia than NBT but with no synergistic effect and it could keep CK-MB leve high in myocardial tissues.

• 생명과학회지
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• 제17권11호
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• pp.1539-1546
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• 2007

연구저자들은 심장판막 수술 환자를 대상으로 냉각 혈액 심정지액에 마그네슘 첨가(2 g)의 효과를 실험하였다. 수술동안 및 후의 $Mg^{++}$ 농도와 $Ca^{++}$ 농도는 마그네슘군이 대조군보다 유의하게 더 높았다. 수술 후 시기에 총 백혈구 수, CK-MB, troponin-I, interleukin-6의 농도는 마그네슘군이 대조군보다 유의하게 더 낮았다. 수술 후 심방세동 발생률 역시 마그네슘군이 대조군보다 유의하게 더 낮았다. 본 연구의 결과들은 심장수술 시 심정지액에 대한 일정량의 마그네슘 첨가가 특별한 부작용 없이 저마그네슘혈증, 전신염증반응, 심방세동의 발생률을 줄이고 심근보호 효과 역시 가져다줌을 시사하고 있다.

• Journal of Chest Surgery
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• 제23권4호
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• pp.646-653
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• 1990

Currently numerous methods are in use for myocardial protection from the ravages of ischemia and hypoxia. This study was designed to compare with FDP-GIK[Group II, n=8] and GIK cardioplegic solution[Group I, n=8] in ability of myocardial protection and was examined in the isolated working rat heart subjected to long period[120 min] of hypothermic[10 - 15K] ischemic arrest with multidose[every 30 min] cardioplegic infusion. During postischemic reperfusion period 20 min, hemodynamic functions[aortic flow, coronary flow, peak aortic pressure, cardiac output, heart rate], biochemical enzymatic & electrical activities were evaluated. The time from onset of reperfusion to the return of regular sinus rhythm was significantly reduced from 87$\pm$3 sec to 17$\pm$2 sec[P<0.05]. The postischemic recovery of aortic flow was better in the group II [95.1$\pm$3.3% of its preischemic control level] than in the Group I [75.4$\pm$6.8%] [P<0.05]. Cardiac output and stroke volume was also better in the group[91.3$\pm$1.6%, 89.4$\pm$2.6%, respectively] than in the Group I [79.1$\pm$3.7%, 77.0$\pm$4.8%, respectively] [P<0. 05]. Creatine kinase leakage was also significantly reduced from 33.8$\pm$4.9 IU /10 min / gm * dry weight to 15.4$\pm$3.6 IU /10 min /gm * dry weight[P<0.05]. It is suggested that adding FDP to GIK cardioplegic solution improves its ability to protect the heart against long period of hypoxic ischemia.

• Journal of Chest Surgery
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• 제31권6호
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• pp.567-575
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• 1998

최근 심장 분야 수술의 발달로 여러 가지 고난도의 심장 수술과 심장 이식술의 시행이 증가하고 있으며, 술 후 예후에 크게 영향을 주는 심장의 심근 손상 방지에 대한 다각적인 연구가 행해지고 있는데, 수술 및 이식 전후의 허혈기와 재관류시 발생할 수 있는 심근 손상을 최소화하고, 술 후 심근 기능의 조속한 회복을 위한 목적으로 여러 약제 및 방법을 제시하고 있다. 한편 한국에서는 오래 전 부터 만병 통치의 영약으로 전해져 오고 있는 인삼을 이용한 동물 실험 및 임상 경험을 통해 성분 효과에 대한 여러 결과가 보고되고 있고, 심장 기능에 대한 효과도 약리학적 측면에서 많은 결과가 발표되었다. 그런데 여러 분획 추출물 중 ginsenoside Rg1 mixtures에 대해서는 그 결과가 다소 미비한 상태이고 ginsenoside Rb1과의 이원 작용에 대한 결과가 흥미로울 것으로 판단되었으며 여러 저자들의 결과에 차이가 있어 ginsenoside Rg1을 이용하여 심근의 허혈 후 재관류 시행 10분 및 지속적 관류 상태에서의 심근 손상에 대한 심근 보호 정도를 혈역학적 지표 및 관상 혈류를 통한 관류액의 효소치를 측정하여 실험한 결과 심근 허혈 및 재관류 후 심근 손상 방지와 심근 기능 회복에 효과가 있다고 판단되며 향후 약제의 투여 용량에 따른 심근 보호 정도에 관한 실험이 필요할 것으로 사료되고, 인삼 성분 각 분획의 복합 투여에 의한 결과도 재차 확인하여야 할 것으로 생각된다.

• Journal of Chest Surgery
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• 제31권10호
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• pp.924-927
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• 1998

연구배경 : 심근의 허혈 또는 재관류에 의한 세포사에는 괴사 이외에 세포고사가 존재함이 알려져 있다. Bcl-2 단백은 세포질에 존재하는 단백으로 세포고사를 억제하는 기능을 하며 정상심근에서는 발현되지 않으나 심근경색의 급성기에서 발현됨이 보고되어 있다. 본 연구는 가토 허혈-재관류 심근에서 Bcl-2 단백의 발현 여부와 재관류의 시간에 따른 발현의 변화를 알아보고자 하였다. 방법: 평균 무게가 2.9Kg(1.5-4.8Kg)인 가토 39마리를 이용하였다. 허혈-재관류 모델의 각 실험동물에서 좌전하행지를 30분간 결찰한 다음 1, 4, 8, 12, 24시간, 3, 7일 동안 재관류시켰다. 이후 즉시 실험동물을 희생시킨 다음 심장을 적출하여 심근조직을 얻고 10% buffered formalin에 고정하였다. Bcl-2 단백의 발현은 파라핀에 포매된 조직에서 단일클론항체를 이용한 면역조직화학적 염색으로 확인하였다. 결과: 허혈-재관류 심근 중 12, 24시간, 3일 재관류군에서 Bcl-2 단백의 발현을 관찰할 수 있었으며, 특히 24시간 재관류 심근에서 잘 관찰되었다. Bcl-2 양성염색의 심근세포는 위험부위의 구제심근에서 관찰되었다. 결론: Bcl-2 단백은 심근의 허혈-재관류에서 급성기의 비교적 후기에 발현되며, 이는 재관류 초기에서 보다는 후기에서 세포고사를 억제하는데 일부 역할을 할 것으로 사료된다.

• Journal of Chest Surgery
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• 제47권3호
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• pp.233-239
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• 2014

Background: As hypertrophied myocardium predisposes the patient to decreased tolerance to ischemia and increased reperfusion injury, myocardial protection is of utmost importance in patients undergoing aortic valve replacement (AVR) for severe aortic valve stenosis (AS). Methods: Consecutive 314 patients (mean age, $62.5{\pm}10.8$ years; 143 females) with severe AS undergoing isolated AVR were included. Postoperative myocardial injury (PMI) was defined as 1) maximum postoperative creatinine kinase isoenzyme MB or troponin-I levels ${\geq}10$ times of reference, 2) postoperative low cardiac output syndrome or episodes of ventricular arrhythmia, or 3) left ventricular ejection fraction of less than 55% and decrease in left ventricle (LV) ejection fraction of more than 20% of the baseline value. Results: There were 90 patients (28.7%) who developed PMI. There were five cases of early death (1.6%), all of whom had PMI. On multivariable analysis, the use of histidine-tryptophan-ketoglutarate (HTK) solution instead of blood cardioplegia (odds ratio [OR], 3.06; 95% confidence interval [CI], 1.63 to 5.77; p=0.001), greater LV mass (OR, 1.04; 95% CI, 1.01 to 1.07; p=0.007), and increased cardiac ischemic time (OR, 1.13; 95% CI, 1.05 to 1.22; p<0.001) were independent predictors for PMI. Patients who had PMI showed significantly inferior long-term survival than those without PMI (p=0.049). Conclusion: PMI occurred in a considerable proportion of patients undergoing AVR for severe AS and was associated with poor long-term survival. HTK cardioplegia, higher LV mass, and longer cardiac ischemic duration were suggested as predictors of myocardial injury.

• Journal of Chest Surgery
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• 제30권1호
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• pp.27-33
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• 1997

관상동맥 우회술에 있어서 전방성 심정지액 주입에 의한 심근 보호의 한계성으로 심정지액의 적절한 분포를 위한 역행성 심정지액의 사용이 점차 일반화되고 있다. 본 서울대학교병원에서는 1994년 4월부터 1995년 8월까지 관상동맥 우회술을 시행한 95례중 76례에서 역행성 심정 지액을 이용한 관상동맥 우회술을 시행하였다. 남녀 성비는 남자가 48명, 여자가 28명이며, 평균 연령은 58.2$\pm$8.3세였다. 술전 진단으로 불안정성 협심증이 53례(70%), 안정성 협심증이 14례(18%), 심근 경색후 협심증이 6례 (8%), 경퍼적 관상동맥 확장술후 합병증이 2례 (3%), 급성 심근경색증이 1례 (1%)이었다. 술전 관상동맥 조명술상 3중혈관 질환이 42례 (55%), 2중혈관 질환이 11례 (14%), 단일혈관 질환이 10례 (13%), 좌주관상동맥 질환이 13례(17%) 로, 수술시 대복재정맥 이외에 좌측 내유동맥을 이용한 경우가 69례, 우측 내유동맥의 경우 11례, 좌측 요골동맥을 사용한 경우가 6례, 우측 위대망막동맥의 경우가 1례이었다. 환자 1인당 문합은 평균 3.2 $\pm$ 1.1개이었다 심정지액 주입 방법으로는 75례에서 전향성 심정지액 주입으로 심정지를 유도한 후 역행성 심정지액 주입으로 심근보호를 유지하였고, 역행성 심정지액 주입만으로 심정지유도 및 심근보호를 유지한 경우도 1례가 있었다. 역행성 심정 지액을 간헐적으로 주입한 경우가 19례, 계속적으로 주입한 경우가 57례이었으며, 우관상동맥 문합을 시행하였던 39례의 환자에서는 역행성 심정지액 주입법 및 우관상동맥 이식 편을 통한 전향성 심정지액의 동시주입법을 실시하였다. 수술 사망은 없었으며, 수술후 합병증으로는 부정맥이 15례 (20%), 수술후 심근경 색증이 10례 (13%), 저심박출증이 8례(11%),술후 일과성 신경학적 합병증이 7례 (9%),술후 일과성 정신과적 합병증이 6례 (8%), 급성 신부전이 3례 (4%),술후 출혈 및 폐렴이 각각 2례 (3%), 창상 감염과 십이지장 궤양 천공이 각각 1례 (1 %)이었다. 역행성심정 지액을 이용한 심근 보호법은 고위험도의 허혈성 심질환 환자에서의 관상동맥 우회술에서 수술 위험도를 최소화할 수 있는 유용한 심근 보호법이라고 생각된다.

• Journal of Chest Surgery
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• 제25권1호
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• pp.1-16
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• 1992

The quantitatively measured local myocardial perfusion rates with microspheres are used as an objective indicator of even distribution of cardioplegic solution, and the efficacy of the retrograde right atrial route of cardioplegia is evaluated in hearts with various levels of coronary arterial obstruction. After initial antegrade cardioplegia under the median sternotomy and aortic cannulation, 60 hearts from anesthetized New Zealand white rabbits are divided in random order as normal group [ligated left main coronary artery ; MA, MR] and diagonal group [ligated proximal diagonal artery ; LA, LR]. Half of each group [N=10] are perfused with antegrade cardioplegia[A] under the pressure of 100 cmH2O and the other half with retrograde right atrial route[R] under the pressure of 60 cmH2O[St. Thomas cardioplegic solution mixed with measured amount of microspheres]. The myocardium is subdivided into segments as A[atria], RV[right ventricle]. S[septum], LV[normally perfused left ventricular free wall], ROI[ischemic myocardium of left ventricular free wall]. LV and RQI are further divided into N[subendocardium] and P[subepicardium]. The resulting local myocardial perfusion rates and N /P of each group are compared with Wilcoxon rank sum test. The weight of the hearts is 5.94$\pm$0.66g, and there are no statistically significant dif-ferences[p>0.05, ANOVA] between six compared group. The mean flow rate[F: ml /g / min] of MR group is comparable with MA group[p>0.05], but in N and L group, there are significantly depressed F with right atrial route of cardioplegia, which means elevated perfusion resistance with this route. In spite of no significant differences in delivered doses of microsphere[DEL] between compared groups[p>0.05, ANOVA], there are significantly depressed REC and NF in hearts with right atrial cardioplegia which suggests increased requirement of cardioplegic solution with this route. The interventricular septum shows poor perfusion with right atrial route of cardioplegia without obstruction of supplying coronary arteries. But, with obstruction of coronary artery supplying septum as in M group, the flow rate is superior with right atrial route of infusion. The left ventricular free wall perfusion rates of every RQI with R route are superior to that of A route[p<0.05]. But, in LV segments, there are unfavorable effects of right atrial cardioplegia in L group, although the subendocardial perfusion is well maintained in N group. The LV free wall of left main group shows depressed perfusion rates with antegrade route as compared with RQI segments of diagonal group. But, by contraries, there are increased perfusion rates and superior N /P ratio with retrograde right atrial route. It implies more effective perfusion with right atrial route of cardioplegia in more proximal coronary arterial obstruction[i.e., M group as compared with L group]. As a conclusion, all region of ischemia have superior perfusion rates with right atrial car-dioplegia as compared with antegrade route, and especially excellent results can be obtained in hearts with more proximal obstruction of coronary arteries which would otherwise result in more severe ischemic damage. But, the depressed perfusion rates of the segments with normal coronary artery in hearts with coronary arterial obstruction may be a problem of concern with right atrial cardioplegia and needs solution.

• The Korean Journal of Physiology and Pharmacology
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• 제25권2호
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• pp.147-157
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• 2021

Coronary microembolization (CME) is associated with cardiomyocyte apoptosis and cardiac dysfunction. Puerarin confers protection against multiple cardiovascular diseases, but its effects and specific mechanisms on CME are not fully known. Hence, our study investigated whether puerarin pretreatment could alleviate cardiomyocyte apoptosis and improve cardiac function following CME. The molecular mechanism associated was also explored. A total of 48 Sprague-Dawley rats were randomly divided into CME, CME + Puerarin (CME + Pue), sham, and sham + Puerarin (sham + Pue) groups (with 12 rats per group). A CME model was established in CME and CME + Pue groups by injecting 42 ㎛ microspheres into the left ventricle of rats. Rats in the CME + Pue and sham + Pue groups were intraperitoneally injected with puerarin at 120 mg/kg daily for 7 days before operation. Cardiac function, myocardial histopathology, and cardiomyocyte apoptosis index were determined via cardiac ultrasound, hematoxylin-eosin (H&E) and hematoxylin-basic fuchsin-picric acid (HBFP) stainings, and TdT-mediated dUTP nick-end labeling (TUNEL) staining, respectively. Western blotting was used to measure protein expression related to the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β) pathway. We found that, puerarin significantly ameliorated cardiac dysfunction after CME, attenuated myocardial infarct size, and reduced myocardial apoptotic index. Besides, puerarin inhibited cardiomyocyte apoptosis, as revealed by decreased Bax and cleaved caspase-3, and up-regulated Bcl-2 and PI3K/Akt/GSK-3β pathway related proteins. Collectively, puerarin can inhibit cardiomyocyte apoptosis and thus attenuate myocardial injury caused by CME. Mechanistically, these effects may be achieved through activation of the PI3K/Akt/GSK-3β pathway.

• The Korean Journal of Physiology and Pharmacology
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• 제14권1호
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• pp.1-9
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• 2010

AMP-activated protein kinase (AMPK) protects various tissues and cells from ischemic insults and is activated by many stimuli including mechanical stretch. Therefore, this study investigated if the activation of AMPK is involved in stretch-induced cardioprotection (SIC). Intraventricular balloon and aorto-caval shunt (ACS) were used to stretch rat hearts ex vivo and in vivo, respectively. Stretch preconditioning reduced myocardial infarct induced by ischemia-reperfusion (I/R) and improved post-ischemic functional recovery. Phosphorylation of AMPK and its downstream substrate, acetyl-CoA carboxylase (ACC) were increased by mechanical stretch and ACC phosphorylation was completely blocked by the AMPK inhibitor, Compound C. AMPK activator (AICAR) mimicked SIC. Gadolinium, a blocker of stretch-activated ion channels (SACs), inhibited the stretch-induced phosphorylation of AMPK and ACC, whereas diltiazem, a specific L-type calcium channel blocker, did not affect AMPK activation. Furthermore, SIC was abrogated by Compound C and gadolinium. The in vivo stretch induced by ACS increased AMPK activation and reduced myocardial infarct. These findings indicate that stretch preconditioning can induce the cardioprotection against I/R injury, and activation of AMPK plays an important role in SIC, which might be mediated by SACs.