• 한국산학기술학회:학술대회논문집
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• 한국산학기술학회 2011년도 추계학술논문집 1부
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• pp.170-173
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• 2011

Therapeutic hypothermia(TH) improves neurological outcomes and reduces mortality among survivors of out-of-hospital cardiac arrest. Animal and human studies have shown that TH results in improved salvage of the myocardium, reduced infarct size, reduced left ventricular remodeling and better long-term left ventricular function in settings of regional myocardial ischemia. This study is to investigate the effect of TH on post-resuscitation myocardial dysfunction and survival time after cardiac arrest and resuscitation in a rat model of myocardial infarction (MI). Thoracotomies were performed in 10 Male Sprague-Dawley rats weighing 450-550 g. MI was induced by ligation of the left anterior descending coronary artery (LAD). Ninety min after LAD ligation, ventricular fibrillation induction and subsequent cardiopulmonary resuscitation was performed before defibrillation attempts. Animals were randomized to two groups: a) Acute MI-Normothermia b) Acute MI-Hypothermia ($32^{\circ}C$ for 4 h). Myocardial functions, including cardiac output, left ventricular ejection fraction, and myocardial performance index were measured echocardiographically together with duration of survival. Ejection fraction, cardiac output and myocardial performance index were $54.74{\pm}9.16$, $89.00{\pm}8.89$, $1.30{\pm}0.09$ respectively and significantly better in the TH group than those of the normothermic group at the first 4 h after resuscitation($32.20{\pm}1.85$,$41.60{\pm}8.62$,$1.77{\pm}0.19$)(p=0.00). The survival time of the hypothermic group ($31.8{\pm}14.8$ h) was greater than that of the normothermic group($12.3{\pm}6.5$ h, p<0.05). This study suggested that TH attenuated post resuscitation myocardial dysfunction in acute MI and would be a potential strategy in post resuscitation care.

• Preventive Nutrition and Food Science
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• 제17권3호
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• pp.177-183
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• 2012

Interruption of blood flow through coronary arteries and its subsequent restoration triggers the generation of a burst of reactive oxygen species (ROS), leading to myocardial cell death. In this study, we determined whether a methanol extract of Cassia mimosoides var. nomame Makino could prevent myocardial ischemia-reperfusion injury. When radical scavenging activity of the extract was measured in vitro using its ${\alpha}$,${\alpha}$-diphenyl-${\beta}$-picrylhydrazyl (DPPH) radical quenching ability, the extract showed an activity slightly lower than that of ascorbic acid. Three days after oral administration of the extract (400 mg/kg/day) to rats, myocardial ischemia/reperfusion injury was generated by 30 min of ligation of the left anterior descending coronary artery (LAD), followed by 3 hr reperfusion. Compared with the vehicle-treated group, administration of the extract significantly reduced infarct size (IS) (ratio of infarct area to area at risk) in the extract-treated group by 28.3%. Reduction in the cellular injury was mediated by attenuation of Bax/Bcl-2 ratio by 33.3%, inhibition of caspase-3 activation from procaspase-3 by 40%, and subsequent reduction in the number of apoptotic cells by 66.3%. These results suggest that the extract attenuates myocardial injury in a rat model of ischemia-reperfusion by scavenging ROS, including free radicals, and consequently blocking apoptotic cascades. Therefore, intake of Cassia mimosoides var. nomame Makino might be beneficial for preventing ischemic myocardial injury.

• 한국동물위생학회지
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• 제31권2호
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• pp.175-186
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• 2008

To diagnose acute myocardial infarction (MI), many cardiac markers have been used in hematologic and biochemical analysis, and many studies have been published for hematologic and biochemical analysis associated with human acute MI. However, after occurrence of acute MI, the serial investigation for values in hematologic and biochemical analysis including chronic MI has rarely been performed. To observe the change of the serial values in hematologic and biochemical analysis, we induced artificial MI. The left main descending artery (LMDA) of the left coronary artery was ligated during the progression (day 1, 3, 5, 7, 14 and 30) of MI. Total 66 Sprague-Dawley rats were divided into the sham group (n=24, thoracotomy without LMDA ligation) and the experimental (MI) group (n=42, with LMDA ligation). And all individual in each group was sacrified at day 1, 3, 5, 7, 14 and 30 for the hematologic and biochemical analysis. In comparison of hematologic analysis between the sham and MI groups, the mean values of red blood cell (RBCs), hemoglobin and hematocrit (HCT) showed a steady increase. In biochemical analysis, the mean values of glucose, cholesterol, total creatine kinase (CK) and isoenzyme MB, and lactate dehydrogenase (LDH) were increased in all MI groups compared with the sham groups. The results of this study suggest that early hematologic and biochemical mean values occurred after acute MI are similar to those of human acute MI. In conclusion, we could observe the alterations and serial values in hematologic and biochemical analysis to the extent of chronic status after acute MI.

• Biomolecules & Therapeutics
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• 제28권5호
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• pp.482-489
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• 2020

G protein-coupled receptor kinase 5 (GRK5) has been considered as a potential target for the treatment of heart failure as it has been reported to be an important regulator of pathological cardiac hypertrophy. To discover novel scaffolds that selectively inhibit GRK5, we have identified a novel small molecule inhibitor of GRK5, KR-39038 [7-((3-((4-((3-aminopropyl)amino)butyl)amino)propyl)amino)-2-(2-chlorophenyl)-6-fluoroquinazolin-4(3H)-one]. KR-39038 exhibited potent inhibitory activity (IC₅₀ value=0.02 µM) against GRK5 and significantly inhibited angiotensin II-induced cellular hypertrophy and HDAC5 phosphorylation in neonatal cardiomyocytes. In the pressure overload-induced cardiac hypertrophy mouse model, the daily oral administration of KR-39038 (30 mg/kg) for 14 days showed a 43% reduction in the left ventricular weight. Besides, KR-39038 treatment (10 and 30 mg/kg/day, p.o.) showed significant preservation of cardiac function and attenuation of myocardial remodeling in a rat model of chronic heart failure following coronary artery ligation. These results suggest that potent GRK5 inhibitor could effectively attenuate both cardiac hypertrophy and dysfunction in experimental heart failure, and KR-39038 may be useful as an effective GRK5 inhibitor for pharmaceutical applications.

• The Korean Journal of Physiology and Pharmacology
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• 제26권2호
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• pp.87-94
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• 2022

Myocardial infarction promotes cardiac remodeling and myocardial fibrosis, thus leading to cardiac dysfunction or heart failure. Peiminine has been regarded as a traditional anti-fibrotic Chinese medicine in pulmonary fibrosis. However, the role of peiminine in myocardial infarction-induced myocardial injury and fibrosis remained elusive. Firstly, rat model of myocardial infarction was established using ligation of the left coronary artery, which were then intraperitoneally injected with 2 or 5 mg/kg peiminine once a day for 4 weeks. Echocardiography and haemodynamic evaluation results showed that peiminine treatment reduced left ventricular end-diastolic pressure, and enhanced maximum rate of increase/decrease of left ventricle pressure (± dP/dt max) and left ventricular systolic pressure, which ameliorate the cardiac function. Secondly, myocardial infarction-induced myocardial injury and infarct size were also attenuated by peiminine. Moreover, peiminine inhibited myocardial infarction-induced increase of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α production, as well as the myocardial cell apoptosis, in the rats. Thirdly, peiminine also decreased the myocardial fibrosis related protein expression including collagen I and collagen III. Lastly, peiminine reduced the expression of p38 and phosphorylation of extracellular signal-regulated kinase 1/2 in rat model of myocardial infarction. In conclusion, peiminine has a cardioprotective effect against myocardial infarction-induced myocardial injury and fibrosis, which can be attributed to the inactivation of mitogen-activated protein kinase pathway.

• Journal of Chest Surgery
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• 제40권5호
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• pp.329-340
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• 2007

배경: Matrix metalloproteinase (MMP) 차단은 심근경색 후 좌심실 확장에 대한 가능한 치료 전략으로 대두되고 있다. 선택적 MMP 차단제의 투여가 심근경색 후 초기 단계에 MMP가 대량으로 분비되는 짧은 기간을 차단하는 것이 좋을 것인지, 초기 전체 기간 동안 차단하여야 할 것인지를 알아보고자 하였다. 대상 및 방법: 토끼를 이용하여 기관 삽관 하에 전신 마취를 하고 흉골 정중절개한 다음 좌전 하행지 관상동맥을 결찰하여 심근경색을 만들었다. 실험군은 3군으로 나누었다. 심근경색 단독(MI only 군)군은 7예, MMP 차단제 5일 투여군(MMPI 5d 군)은 6예, MMP 차단제 9일 투여군(MMPI 9d 군)은 5예이었다. MMP 차단제로는 MMP-2와 MMP-9에 대한 선택적 차단제인 CG2300을 사용하였다. 각 군은 심장초음파도 검사를 4회 시행하였는데, 술 전, 술 후 1주, 2주 및 3주에 하였다. 검사는 2D 심초음파도를 사용하여 EDD, ESD 및 EF를 측정하였다. 술 후 4주에 희생한 토끼의 심장을 western blotting과 zymography를 하여 MMP-2와 MMP-9의 단백질과 활성의 변화를 조사하였고, 경색부위를 병리학적 조직검사를 하였다. 결과: 심초음파도 검사상, MI only군에서는 대체로 술 전에 비하여 술 후 EDD와 ESD가 증가한 추세로 좌심실이 확장하였음을 알 수 있었다. MMP 차단제 9일 투여군에서는 심근경색 단독군과 MMP 차단제 5일 투여군에 비해 좌심실의 확장이 감소한 경향을 보였다. EF는 MMP 차단제 9일 투여군에서 술 후에 술 전과 큰 변동이 없었으며, 다른 군들보다 높은 경향이었다. MMP 단백질의 발현과 활성 변화를 보면, 심근경색 단독군, MMP 차단제 5일 및 9일 투여군 등 3군을 정상 심장군과 비교하였을 때 MMP-2 단백질 발현과 활성 변화는 일어나지 않았다. 그리고 MMP-9의 단백 발현 및 활성은 검출되지 않았다. 병리학적 조직 소견을 보면 심근경색 단독군에서 심한 교원질 침착이 있었다. MMP 차단제 5일 투여군과 9일 투여군에서는 교원질 축적이 감소된 경향을 보였다. MMP 9일 투여군에서는 모세혈관의 수가 증가한 것을 볼 수 있었다. 결론: 관상동맥을 결찰하여 심근경색을 유도하면 술 후 빠른 시간 내에 심실이 확장되며 MMP 차단제를 투여할 경우 심실의 확장이 완화됨을 알 수 있었다. MMP 차단제의 효과는 초기의 대부분 기간을 차단하는 것이 좋다고 생각된다. MMP 차단제가 혈관신생을 증가시켜 심실 재형성을 완화할 수 있는 것으로 분석된다.

• 한국응급구조학회지
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• 제20권2호
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• pp.7-19
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• 2016

연구 목적: 본 연구에서는 심근경색 쥐 모델에서 심장정지를 유발시킨 후 심폐소생술을 수행하는 과정에서 조기 저체온 치료를 적용하여 심장근육의 기능회복과 생존율에 미치는 효과를 조사하고자 하였다. 연구 방법: 본 연구를 위하여 체중 450-550g의 수컷 Sprague Dawley 쥐 10 마리에 개흉을 실시하였다. 왼내림심장동맥을 묶어서 심근경색을 유발시켰다. 왼내림심장동맥을 묶은 후 90분 동안 심실세동을 유도하고, 심폐소생술과 제세동을 실시하였다. 대조군(정상체온군)은 회복과정에 정상체온으로 유지한 군이며, 실험군(저체온군)은 회복과정에 $32^{\circ}C$ 4시간 저체온을 유지한 군이다. 연구 결과: 심박출량, 좌심실박출률, 심근수행지수는 심폐소생술 후 첫 4시간 동안 대조군보다 실험군에서 더 양호하게 나타났다. 실험군의 생존시간은 대조군보다 더 길게 나타났다(p<.050). 결 론: 본 연구를 통하여 조기 저체온 치료의 적용이 급성심근경색의 심폐소생술 후 심장 기능을 개선하는 데 탁월한 효과가 있으며, 치료법의 새로운 기준이 될 것이다.

• Journal of Chest Surgery
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• 제38권5호
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• pp.323-334
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• 2005

배경: 유전자 치료에 의한 치료적 혈관조성은 허혈성 심질환의 새로운 치료전략의 하나로 최근 많은 연구가 진행되고 있다. 본 연구의 목적은 대동물에서 pCK 플라스미드 벡터에 혈관내피성장인자(vascular endothelial growth factor isoform 165: VEGF165) 유전자를 삽입한 pCK-VEGF를 이용한 치료적 혈관조성의 효용성을 증명하는 것이다. 대상 및 방법: 총 21 마리의 돼지를 이용하여 좌전하행지동맥의 원위부를 결찰하여 심근경색 모델을 만든 후, 4주 후에 VEGF 유전자를 삽입한 플라스미드를 심근내에 주입하거나(VEGF군), 유전자 없이 플라스미드 만을 주입하였다(대조군). 실험 대상 동물군을 맹검하에 무작위로 VEGF군 및 대조군으로 나누어 실험을 진행하였는데, 7마리는 실험 도중 사망하였으며 결과적으로 VEGF군은 8마리, 대조군은 6마리가 최종분석에 이용되었다. 좌전하행지동맥 결찰 후 30일째에 심근 SPECT와 심장초음파검사를 시행하고 심근내에 플라스미드를 주입하였으며, 이로부터 30일째에 심근 SPECT와 심장초음파검사를 다시 시행하였다. 허혈부위의 심근관류의 변화는 심근 SPECT상의 $^{99m}Tc-MIBI$의 섭취 정도로 비교하였으며, 국소 및 전체 심근기능 및 심실리모델링 등은 심장초음파 또는 게이트SPECT 검사상의 수축시 심실벽비후화, 좌심실구출률(EF), 수축기말용적(ESV), 이완기말용적(EDV) 등으로 비교하였다. 혈관조성의 정도는 조직검사상의 미세혈관의 밀도를 측정하여 비교하였다. 결과: 미세혈관의 밀도는 VEGF군에서 유의하게 더 높았으며($386\pm110/mm^{2}\;vs.\;291\pm127/mm^{2},\;p<0.001$), 분절의 관류 정도도 VEGF군에서는 관상동맥 결찰 60일째가 30일째에 비해 더 증가한 반면(플라스미드 주입 전, 후, $48.4\pm15.2\%\;vs.\;53.8\pm19.6\%,\;p<0.001$) 대조군에서는 유의한 변화가 없었고(플라스미드 주입 전, 후, $45.1\pm17.0\%\;vs.\;43.4\pm17.7\%,\;p=0.186$), 그 변화량도 두 군간에 유의한 차이를 보였다($11.4\pm27.0\%$ 증가 vs $2.7\pm19.0\%$ 감소, p=0.003). 수축시의 심실벽비후화는 양 군 모두에서 플라스미드 주입 후 유의하게 증가하였으나 증가한 정도는 두 군간에 차이가 없었다. 심장초음파검사상 ESV은 양 군 모두에서 수술 전에 비해 관상동맥 결찰 후 유의하게 증가하였고 (VEGF군, $22.9\pm9.9\;mL\;vs.\;32.3\pm9.1\;mL,\;p=0.006;$ 대조군, $26.3\pm12.0\;mL\;vs.\;36.8\pm9.7\;mL,\;p=0.046$), EF은 유의하게 감소하였으며(VEGF군, $52.0\pm7.9\%\;vs\;46.5\pm7.4\%$, p=0.004; 대조군, $48.2\pm9.2\%\;vs\;41.6\pm10.0\%$, p=0.028), EDV은 양 군 모두에서 유의한 변화가 없었다. 플라스미드 주입 전과 후의 비교에서는 양 군 모두에서 심장초음파 및 게이트 SPECT검사상의 EF, ESV, EDV 값의 유의한 차이가 없었다. 결론: VEGF165 유전자를 삽입한 플라스미드의 심근내 주입 후 허혈성 생존 심근 부위에 혈관조성이 일어나고 심근관류가 유의하게 증가하였다. 그러나 심근 기능이나 좌심실의 리모델링 경과엔 유의한 차이가 없었다.

• Applied Microscopy
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• 제22권1호
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• pp.42-54
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• 1992

To understand the structural changes of the myocardial myocytes and endothelial cells in ischemic and reperfused heart, and to elucidate their roles in those conditions, the authors observed cat and rat myocardium ultrastructurally and evaluated them with morphometric techniques. In cat, mild ischemia and moderate degree reperfusion injury was induced by ligation of the anterior interventricular branch of left coronary artery and reperfusion. In rat, severe ischemia and irreversible reperfusion iniury was made using in vitro Langendorff techniques. In normal cat myocytes, the volume densities of cytoplasm, myofibrils, mitochondria, sarcoplasmic reticulum and T tubules were $0.11{\pm}0.013,\;0.51{\pm}0.096,\;0.25{\pm}0.082,\;0.09{\pm}0.008,\;0.02{\pm}0.010$ (Mean${\pm}$S.D.) respectively, and the myofibril/mitochondria ratio was $2.33{\pm}1.379$. The numerical density and average volume of mitochondria were $0.76{\pm}0.210/{\mu}m^3$ and $0.33{\pm}0.057{\mu}m^3$ respectively. In normal cat endothelial cells, the volume densities of cytoplasm, cytoplasmic vesicles, tubular systems (including endoplasmic reticulum and Golgi apparatus) and mitochondria were $0.43{\pm}0.023,\;0.28{\pm}0.007,\;0.22{\pm}0.021,\;0.03{\pm}0.014$ respectively. The mean thickness of endothelial cells was $230{\pm}45.2{\mu}m$. The numerical density and average volume of cytoplasmic vesicles were $508{\pm}55.0/{\mu}m^3,\;578{\pm}104.8nm^3$ respectively. In cat myocytes which received mild ischemic injury, the volume densities of organelles were not changed significantly in ischemic and reperfusion states. In reperfusion group myocytes, the numerical density of mitochondria was decreased significantly and the average volume was increased significantly. In endothelial cells, the volume density of tubular system in ischemic group and the average volume of cytoplasmic vesicles in reperfusion group were increased significantly. In rat myocytes which received severe ischemic injury, the volume density and average volume of mitochondria were increased significantly, and the volume density of sarcoplasmic reticulum and numerical density of mitochondria were decreased significantly in both ischemic and reperfusion groups. In ischemic and reperfused endothelial cells, the volume density and numerical density of cytoplasmic vesicles, the volume density of cytoplasm were decreased significantly. The volume densities of tubular system were increased significantly in both ischemic and reperfused groups. The volume density of mitochondria in ischemic group and the average volume of cytoplasmic vesicles in reperfusion group showed significant increase. The authors, based on the above observations, conclude that the mitochondria of myocytes and the cytoplasmic vesicles of endothelia are the first group of targets in ischemic and reperfusion injury and in this respect, the degree of ischemic insult is not significant. The role of myocyte mitochondria in reperfusion injury may be insignificant, but endothelial cells may contribute actively to reperfusion injury.

• 대한한의학방제학회지
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• 제31권3호
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• pp.157-169
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• 2023

Gracilaria Verrucosa (GV), a seaweed used in traditional Korean medicine, was studied for its effects on MI-induced heart failure in rats. MI is caused by a blocked coronary artery, leading to severe cardiac dysfunction. The study used a rat model to assess cardiac changes over time and evaluate the impact of GV on heart failure. Ischemia was induced through LAD ligation surgery, and the extent of ischemic area was measured as a prognostic factor. GV extract administration significantly improved cardiac morphology and reduced cardiac weight compared to the MI group. GV treatment also improved cardiac function, as evidenced by positive effects on chamber dilation during MI-induced heart failure. Parameters such as ejection fraction (EF) and fractional shortening (FS) were measured. The MI group showed decreased EF and FS compared to the sham group, while these parameters improved in the GV group. GV treatment also reduced levels of LDH, CPK, and CK-MB in the serum, indicating reduced myocardial damage. Histological analysis revealed that GV treatment attenuated cardiac hypertrophy and fibrosis, with reduced collagen deposition in the myocardium. Immunohistochemistry analysis showed suppressed expression of TGF-β1 and collagen 1, involved in fibrosis. In conclusion, GV showed potential in improving cardiac function in a rat model of MI-induced heart failure. It alleviated myocardial damage, attenuated cardiac hypertrophy and fibrosis, and suppressed fibrotic markers. Further studies are needed to explore its clinical efficacy and underlying mechanisms in cardiac diseases beyond animal models.