• Journal of Chest Surgery
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• 제33권3호
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• pp.213-220
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• 2000

Background: Adhesion of leukocytes to myocardium or vascular endothelium has been known as an importation initial step in the ischemia-reperfusion injury which may affect the cardiac function. Therefore, leukocyte-depleted reperfusion may inhibit ischemia-reperfusion induced functional and ultrastructural deterioration. In this study, we quantified the time-dependent expression of the vascular cell adhesion molecule-1(VCMA-1) on piglet myocardium and demonstrated its relation to functional recovery using isolated piglet heart perfusion model. Material and Method: Neonatal(1 to 3 day old) piglet heart was harvested with 4$^{\circ}C$ University of Wisconsin solution (UWS) and presrved in the same solution for 12 hours. Ex vivo model of an isolated working neonatal piglet heart perfusion consisting of membrane oxygenator and roller-pump was used (Fig. 1). Hearts were grouped into leukocyte-non-depleted (group A, n=8) and leukocyte-depleted group(group B, n=8). In group B, hearts were reperfused with leukocyte-depleted blood using a leukocyte filter (Sepacell R, Asahi Medical, Japan). Segments of right atrium were taken before and after 1, 2, 3, and 4 hours of reperfusion for the evaluation of expression of VCAM-1. The intensity of immunohistochyemical satining of the VCAM-1 on the myocardium were graded semiquantitatively (0 to 4). For the evaluation of myocardial stroke work indices were calculated as well at the same time-points. Result: Mean expressins of VCAM-1 on the myocardium at 0, 1, 2, 3, adn 4 hours of reperfusion were 0.63, 1.44, 1.64, 2.65, and 3.34 in group A, while 0.56, 1.40, 1.50, 1.88 and 2.14 in group B (Fig. 3). Mean stroke work indices at 0.5, 1, 2, 3, and 4 hours after reperfusion were 1.35$\times$104, 1.32$\times$104, 1.14$\times$104, 0.81$\times$104, 0.68$\times$104 erg/gm in group A, while 1.40$\times$104, 1.43$\times$104, 1.43$\times$104, 1.28$\times$104, and 1.12$\times$104 erg/em in group B(Fig. 4). Conclusion : In this study, we demonstrated that leukocyte-depletion attenuated the expression of VCAM-1 during reperfusion and the time-dependent functional deterioration of the myocardium was well correlated with the degree of VCAM-1 expression.

• Journal of Chest Surgery
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• 제44권3호
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• pp.208-214
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• 2011

Background: Periprocedural treatment with high-dose statins is known to have cardioprotective and pleiotropic effects, such as anti-thrombotic and anti-inflammatory actions. We aimed to assess the efficacy of high-dose rosuvastatin loading in patients with stable angina undergoing off-pump coronary artery bypass grafting (OPCAB). Materials and Methods: A total of 142 patients with stable angina who were scheduled to undergo surgical myocardial revascularization were randomized to receive either pre-treatment with 60-mg rosuvastatin (rosuvastatin group, n=71) or no pre-treatment (control group, n=71) before OPCAB. The primary endpoint was the 30-day incidence of major adverse cardiac events (MACEs). The secondary endpoint was the change in the degree of myocardial ischemia as evaluated with creatine kinase-myocardial band (CK-MB) and troponin T (TnT). Results: There were no significant intergroup differences in preoperative risk factors or operative strategy. MACEs within 30 days after OPCAB occurred in one patient (1.4%) in the rosuvastatin group and four patients (5.6%) in the control group, respectively (p=0.37). Preoperative CK-MB and TnT were not different between the groups. After OPCAB, the mean maximum CK-MB was significantly higher in the control group (rosuvastatin group $10.7{\pm}9.75$ ng/mL, control group $14.6{\pm}12.9$ ng/mL, p=0.04). Furthermore, the mean levels of maximum TnT were significantly higher in the control group (rosuvastatin group $0.18{\pm}0.16$ ng/mL, control group $0.39{\pm}0.70$ ng/mL, p=0.02). Conclusion: Our findings suggest that high-dose rosuvastatin loading before OPCAB surgery did not result in a significant reduction of 30-day MACEs. However, high-dose rosuvastatin reduced myocardial ischemia after OPCAB.

• The Korean Journal of Physiology and Pharmacology
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• 제20권3호
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• pp.305-314
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• 2016

Inflammatory and fibrotic responses are accelerated during the reperfusion period, and excessive fibrosis and inflammation contribute to cardiac malfunction. NecroX compounds have been shown to protect the liver and heart from ischemia-reperfusion injury. The aim of this study was to further define the role and mechanism of action of NecroX-5 in regulating inflammation and fibrosis responses in a model of hypoxia/reoxygenation (HR). We utilized HR-treated rat hearts and lipopolysaccharide (LPS)-treated H9C2 culture cells in the presence or absence of NecroX-5 ($10{\mu}mol/L$) treatment as experimental models. Addition of NecroX-5 significantly increased decorin (Dcn) expression levels in HR-treated hearts. In contrast, expression of transforming growth factor beta 1 ($TGF{\beta}1$) and Smad2 phosphorylation (pSmad2) was strongly attenuated in NecroX-5-treated hearts. In addition, significantly increased production of tumor necrosis factor alpha ($TNF{\alpha}$), $TGF{\beta}1$, and pSmad2, and markedly decreased Dcn expression levels, were observed in LPS-stimulated H9C2 cells. Interestingly, NecroX-5 supplementation effectively attenuated the increased expression levels of $TNF{\alpha}$, $TGF{\beta}1$, and pSmad2, as well as the decreased expression of Dcn. Thus, our data demonstrate potential antiinflammatory and anti-fibrotic effects of NecroX-5 against cardiac HR injuries via modulation of the $TNF{\alpha}/Dcn/TGF{\beta}1/Smad2$ pathway.

• 한국방사선학회논문지
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• 제10권7호
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• pp.511-519
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• 2016

좌심실 이완기능 장애는 심근허혈이나 좌심실비대 등과 같은 심근질환이 잇는 환자에서 대부분 관찰되지만 심장질환이 없는 건강한 사람에서도 흔하게 관찰된다. 정상 심박출(수축기능)상태에서 좌심실의 이완기 장애 평가는 심부전의 진행과 예후에 영향을 줄 수 있다. 심장외막지방조직은 생리활성분자를 생성하는 대사활동기관으로 심혈관질환에 직접적으로 연관성이 있으며 이는 심근에 직접적으로 영향을 미쳐 이후 심장의 기능장애를 초래한다. 본 연구목적은 심장외막지방의 두께를 측정하여 정상의 수축기 기능인 상태에서 확장기(이완기) 기능장애의 평가와의 연관성을 연구하고자하였다. 연구결과 심장외막지방두께와 이완기 장애 유무가 통계적으로 유의한 수준에서 높은 연관성이 있는 것으로 분석되었다. 특히 심장외막지방두께 측정단면 EAT2에서 측정된 값과 이완기 장애평가방법 E'는 높은 상관관계가 있는 것으로 나타났다. 따라서 심장외막지방두께변화는 좌심실의 이완기능장애를 평가할 수 있는 예측인자로 사용될 수 있을 것으로 사료된다.

• The Korean Journal of Physiology and Pharmacology
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• 제8권2호
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• pp.95-100
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• 2004

Ischemic preconditioning (IPC) has been accepted as a heart protection phenomenon against ischemia and reperfusion (I/R) injury. The activation of ATP-sensitive potassium $(K_{ATP})$ channels and the release of myocardial nitric oxide (NO) induced by IPC were demonstrated as the triggers or mediators of IPC. A common action mechanism of NO is a direct or indirect increase in tissue cGMP content. Furthermore, cGMP has also been shown to contribute cardiac protective effect to reduce heart I/R-induced infarction. The present investigation tested the hypothesis that $K_{ATP}$ channels attenuate DNA strand breaks and oxidative damage in an in vitro model of I/R utilizing rat ventricular myocytes. We estimated DNA strand breaks and oxidative damage by mean of single cell gel electrophoresis with endonuclease III cutting sites (comet assay). In the I/R model, the level of DNA damage increased massively. Preconditioning with a single 5-min anoxia, diazoxide $(100\;{\mu}M)$, SNAP $(300\;{\mu}M)$ and 8-(4-Chlorophenylthio)-guanosine-3',5'-cyclic monophosphate (8-pCPT-cGMP) $(100\;{\mu}M)$ followed by 15 min reoxygenation reduced DNA damage level against subsequent 30 min anoxia and 60 min reoxygenation. These protective effects were blocked by the concomitant presence of glibenclamide $(50\;{\mu}M)$, 5-hydroxydecanoate (5-HD) $(100\;{\mu}M)$ and 8-(4-Chlorophenylthio)-guanosine-3',5'-cyclic monophosphate, Rp-isomer (Rp-8-pCPT-cGMP) $(100\;{\mu}M)$. These results suggest that NO-cGMP-protein kinase G (PKG) pathway contributes to cardioprotective effect of $K_{ATP}$ channels in rat ventricular myocytes.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2003년도 생물공학의 동향(XIII)
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• pp.164-166
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• 2003

본 연구에서는 손상된 심근의 재생을 위하여 골수단핵세포를 피브린 고분자와 함께 SD 래트에 이식하였고 8주 후에 신생혈관의 형성과 더불어 심장의 기능이 향상되었음을 확인할 수 있었다. 이 연구는 세포이식을 통한 조직 재생시 세포 이식용 매트릭스의 중요성을 보여준다. 환자 자신의 골수세포를 사용한다면 면역 문제가 없어서, 이 방법이 심부전 환자의 치료에 쉽게 이용될 수 있을 것이다.

• Journal of Chest Surgery
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• 제20권4호
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• pp.643-654
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• 1987

The effect of prostacyclin[PGI, ] on myocardial preservation during global ischemia was studied in the isolating working rabbit heart model. Forty hearts underwent a 15 minute period of retrograde nonworking perfusion with Krebs-Henseleit buffer solution [37*C] and were switched over to the working mode for 15 minutes. After baseline measurement of heart rate, peak aortic pressure, aortic flow, and coronary flow, all hearts were subjected to 60 minutes of ischemic arrest at 10*C induced with St. Thomas Hospital cardioplegic solution: Group I had single dose cardioplegia, Croup II double dose, Croup III oxygenated double dose, and Group IV single dose with PCI, infusion [10ng/min./gm heart weight]. Hearts were then revived with 15 minute period of nonworking reperfusion at normothermia, followed by 30 minutes of working perfusion. Repeat measurements of cardiac function were obtained and expressed as a percent of the preischemic baseline values. Oxygen content of arterial perfusate and coronary effluent was measured by designed time interval. Leakage of creatine kinase was determined during post-ischemic reperfusion period. Finally wet hearts were weighed and placed in 120*C oven for 36 hours for measurement of dry weight. In the PGI, treated group [IV], heart rate increased consistently throughout the period of reperfusion from 100*5.0% [p<0.001] to 107*6.2% [p<0.001]. The percent recovery of aortic flow showed 95*5.7% [p<0.001] at the first 3 minute and full recovery through the subsequent time. Coronary flow was augmented significantly in the 3 minute [96*6.2%, p<0.001] and then sustained above baseline values. Among the Croup I, II, and III, all hemodynamic values were significantly below preischemic levels. PGI2 relatively increased oxygen delivery [1.22*0.19ml/min, p<0.001] and myocardial oxygen consumption [0.90*0.13ml/min, p<0.001] during reperfusion period. Leakage of creatine kinase in the PGI2 group was 9.3*1.58IU/15min [p<0.001]. This was significantly lower than Group I [33.0*2.68 IU/15min]. The water content of PCI2 treated hearts [81*0.9%, p<0.001] was also lower than the other groups.

• The Korean Journal of Physiology and Pharmacology
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• 제7권6호
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• pp.333-339
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• 2003

It has been demonstrated that an unidentified cytosolic factor(s) reduces $K_{ACh}$ channel function. Therefore, this study attempted to elucidate the cytosolic factor. Fresh cytosol isolated from normal heart (FC) depressed the $K_{ACh}$ channel activity, but cytosol isolated from the ischemic hearts (IC) did not modulate the channel function. Electrophorectic analysis revealed that a protein of ${\sim}80 kDa was markedly reduced or even lost in IC. By using peptide sequencing analysis and Western blot, this 80 kDa protein was identified as transferrin (receptor-mediated $Fe^{3+}$ transporter, 76 kDa). Direct application of transferrin (100 nM) to the cytoplasmic side of inside-out patches decreased the open probability ($P_o$, 12.7${\pm}6.4%, n=4) without change in mean open time (${\tau}_o$, $98.5{\pm}1.3$%, n=4). However, the equimolar apotransferrin, which is free of $Fe^{3+}$, had no effect on the channel activity (N*$P_o$, $129.1{\pm}13.5$%, n=3). Directly applied $Fe^{3+}$ (100 nM) showed results similar to those of transferrin (N*$P_o$: $21.1{\pm}3.9$%, n=5). However $Fe^{2+}$ failed to reduce the channel function (N*$P_o$, $106.3{\pm}26.8$%, n=5). Interestingly, trivalent cation La3+ inhibited N*$P_o$ of the channel ($6.1{\pm}3.0$%, n=3). Taken together, these results suggest that $Fe^{3+}$ bound to transferrin can modulate the $K_{ACh}$ channel function by its electrical property as a polyvalent cation.

• 한국의료질향상학회지
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• 제10권2호
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• pp.216-231
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• 2003

Objectives: To develop a model that predicts a death probability of acute myocardial infarction(AMI) patient, and to evaluate a performance of hospital services using the developed model. Methods: Medical records of 861 AMI patients in 7 general hospitals during 1996 and 1997 were reviewed by two trained nurses. Variables studied were risk factors which were measured in terms of severity measures. A risk model was developed by using the logistic regression, and its performance was evaluated using cross-validation and bootstrap techniques. The statistical prediction capability of the model was assessed by using c-statistic, $R^2$ as well as Hosmer-Lemeshow statistic. The model performance was also evaluated using severity-adjusted mortalities of hospitals. Results: Variables included in the model building are age, sex, ejection fraction, systolic BP, congestive heart failure at admission, cardiac arrest, EKG ischemia, arrhythmia, left anterior descending artery occlusion, verbal response within 48 hours after admission, acute neurological change within 48 hours after admission, and 3 interaction terms. The c statistics and $R^2$ were 0.887 and 0.2676. The Hosmer-Lemeshow statistic was 6.3355 (p-value=0.6067). Among 7 hospitals evaluated by the model, two hospitals showed significantly higher mortality rates, while other two hospitals had significantly lower mortality rates, than the average mortality rate of all hospitals. The remaining hospitals did not show any significant difference. Conclusion: The comparison of the qualities of hospital service using risk-adjusted mortality rates indicated significant difference among them. We therefore conclude that risk-adjusted mortality rate of AMI patients can be used as an indicator for evaluating hospital performance in Korea.

• 대한의용생체공학회:의공학회지
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• 제27권4호
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• pp.154-163
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• 2006

A 64-channel magnetocardiogram (MCG) system using low-noise superconducting quantum interference device (SQUID) planar gradiometers was developed for the measurements of cardiac magnetic fields generated by the heart electric activity. Owing to high flux-to-voltage transfers of double relaxation oscillation SQUID (DROS) sensors, the flux-locked loop electronics for SQUID operation could be made simpler than that of conventional DC SQUIDs, and the SQUID control was done automatically through a fiber-optic cable. The pickup coils are first-order planar gradiometers with a baseline of 4 em. The insert has 64 planar gradiometers as the sensing channels and were arranged to measure MCG field components tangential to the chest surface. When the 64-channel insert was in operation everyday, the average boil-off rate of the dewar was 3.6 Lid. The noise spectrum of the SQUID planar gradiometer system was about 5 fT$_{rms}$/$\checkmark$Hz at 100 Hz, operated inside a moderately shielded room. The MCG measurements were done at a sampling rate of 500 Hz or 1 kHz, and realtime display of MCG traces and heart rate were displayed. After the acquisition, magnetic field mapping and current mapping could be done. From the magnetic and current information, parameters for the diagnosis of myocardial ischemia were evaluated to be compared with other diagnostic methods.