• Journal of Chest Surgery
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• v.33 no.2
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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.

• Journal of Life Science
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• v.17 no.11
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• pp.1539-1546
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• 2007

We have investigated whether the supplement of magnesium to cold blood cardioplegia improves myocardial protection. Sixty patients scheduled for elective valvular heart surgery were randomly assigned to a control group (n=30) which received conventional cold blood cardioplegia and an Mg group (n=30) which received cold blood cardioplegia supplemented with 2 g of magnesium sulfate. Electrolytes levels including $Mg^{++}$, hematological and biochemical variables, cytokines, myocardial marker levels, and postoperative outcomes were compared between two groups before, during or idler operation. $Mg^{++}\;and\;Ca^{++}$ levels in the Mg group were higher than those of the control group after surgery. The total WBC counts, CK-MB, troponin-I and Interleukin-6 levels in the Mg group were lower than those of the control group after surgery. Postoperative incidence of atrial fibrillation was lower in the Mg group compared with the control group. These results showed that $Mg^{++}$ attenuated inflammatory reaction, myocardial damage, and hypomagnesemia during valvular surgery and reduced postoperative arrhythmia incidence without side effects.

• Journal of Chest Surgery
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• v.23 no.4
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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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• v.31 no.6
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• pp.567-575
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• 1998

Panax Ginseng C.A. Meyer has been known for hundreds of years as the most valuable drug having mysterious effects among all the herbal medicines and plants in Korea. Also, many experimental studies have been performed recently that the various effects were identified and applied clinically. So we attempted an experimental study on the effect of ginsenoside Rg1 mixtures in an isolated rat heart with the use of the Langendorff model. The objective of this study was to determine whether this ginsenoside Rg1 mixtures would protect the myocardial injury after ischemic arrest and reperfusion. Isolated rat hearts were allowed to equilibrate for 20 minutes and were then subjected to 15 minutes of normothermic ischemia. After this ischemic period, isolated rat hearts were allowed to reperfusion for 10 minutes(Ischemic Group). In other group , isolated rat hearts were perfused for 60 minutes continuously with normothermia( Normothermic Group). Hemodynamic and biochemical parameters such as heart rate, left ventricular pressure, +dp/dt max, coronary blood flow and cardiac enzymes were measured during initial perfusion, ischemia, reperfusion period (Ischemic group) and 20, 40 and 60 minutes after continuous perfusion(Normothermic group). After completion of the experiment, this data was evaluated and the following results were obtained. 1. Heart rates showed an increase in both ischemic and normothermic experimental groups, but statistically significant differences were not identified. 2. LVP(Left Ventricular Pressure) showed statistically significant differences in both ischemic and normothermic experimental groups(p<0.005, p<0.01). 3. +dp/dt max showed statistically significant differences in both ischemic and normothermic experimental groups(p<0.01, p<0.01). 4. There were no statistically significant differences in coronary blood flow and cardiac cenzymes in all groups, but experimental groups seemed to have better protection and recovery. These results suggest that ginsenoside Rg1 mixtures has a protective effect on the myocardial injury after ischemia and reperfusion.

• Journal of Chest Surgery
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• v.31 no.10
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• pp.924-927
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• 1998

Background: Myocardial cell death after myocardial infarction or reperfusion is classified into necrosis and apoptosis. Bcl-2 protein is a cytoplasmic protein, which inhibits apoptosis and is expressed in acute stage of myocardial infarction but not in normal heart. This study was performed to investigate whether Bcl-2 protein was expressed respectively to the reperfusion time. Materials and methods: Thirty nine New Zealand white rabbits weighing 1.5-4.8 kg (mean, 2.9kg) were alloted into 7 groups (n=5 in each group) which underwent left anterior descending coronary artery(LAD) occlusion for 30 minutes, followed by reperfusion. The animals were sacrificed at 1, 4, 8, 12, 24 hours, and 3, 7 days after occlusion. Ventricle was excised immediately after intervention. Tissues were fixed in 10% buffured formalin and embedded in paraffin. Bcl-2 protein was detected by immunohistochemical stain with using monoclonal antibody against Bcl-2 protein. Results: The positive immunohistochemical reactivity for Bcl-2 protein was observed in 12, 24 hours, and 3 days reperfusion groups. Bcl-2 protein was detected in salvaged myocytes surrounding the infarcted area. Conclusions: Bcl-2 protein is expressed at the late acute stage of infarct. Therefore, the expression of Bcl-2 protein may not protect acute cell death, but may play a role in the prevention of late cell death after myocardial is chemia-reperfusion.

• Journal of Chest Surgery
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• v.47 no.3
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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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• v.30 no.1
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• pp.27-33
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• 1997

Retrograde myocardial protection is widely accepted in CABG operation because of the limitations of the antegrade method in the coronary arterial stenosis lesions. We analyzed 76 c ses of retrograde myocardial protection among 96 cases of CABG operation performed between April 1994 and August 1995, There were 48 males and 25 females, and the mean age was 58.2 $\pm$ 8.3 years. 53 patients (70%) were operated for unstable angina, 14 (18%) for stable angina, 6 (8%) for post-infarct angina, 1 (1%) for acute myocardial infarction, and 2()%) for failed PTCA. Preoperative coronary angiography revealed 3-vessel disease in 42 cases, 2-vessel disease in 11, 1-vessel disease in 10, and left main disease in 13 cases. We used SVG(63 cases), LIMA(69 cases), RIMA(11 cases), radial artery(6 cases), and gastroepiploic artery(1 case) for the grafts. Mean anastomosis was 3.2 $\pm$ 1.1. We protected the myocardium with antegrade induction and retrograde maintenance in all the cases except a case of retrograde induction and maintenance. During the aortic cross-clamping, blood cardioplegia was administered intermittently in 19 cases, and continuously in 57 In 39 cases, we used retrograde ardioplegia and antegrade perfusion of RCA graft simultaneously. We had no operative motality. Perioperative complications were arrhythmia in 15 cases, perioperatve myocardial infarction in 10, low cardiac output syndrome In 8, transient neurologic problem in 7, transient psychiatric problem in 6, ARF in 3, bleeding in 2, pneumonia in 2, wound infection in 1, and duodenal ulcer perforation in 1 . In this report, we experienced 76 cases of CABG operation with retrograde myocardial protection under the acceptable operative risk without operative mortality.

• Journal of Chest Surgery
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• v.25 no.1
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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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• v.25 no.2
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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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• v.14 no.1
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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.