• Biomolecules & Therapeutics
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• 제21권5호
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• pp.371-380
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• 2013

Doxorubicin is still main drug in chemotherapy with limitation of use due to adverse drug reaction. Increased oxidative stress and alteration of nitric oxide control have been involved in cardiotoxicity of doxorubicin (DOX). A Disintegrin And Metalloproteinase (ADAMs) are transmembrane ectoproteases to regulate cell-cell and cell-matrix interactions, but role in cardiac disease is unclear. The aim of this study was to determine whether DOX activates peroxynitrite and ADAM 10 and thus ADAM and matrix metalloproteinase (MMP) induce cardiac remodeling in DOX-induced cardiomyopathy. Adult male Sprague-Dawley rats were subjected to cardiomyopathy by DOX (6 times of 2.5 mg/kg DOX over 2-weeks), and were randomized as four groups. Then followed by 3, 5, 7, and 14 days after cessation of DOX injection. DOX-injected animals significantly decreased left ventricular fractional shortening compared with control by M-mode echocardiography. The expressions of cardiac nitrotyrosine by immunohistochemistry were significant increased, and persisted for 2 weeks following the last injection. The expression of eNOS was increased by 1.9 times (p<0.05), and iNOS was marked increased in DOX-heart compared with control (p<0.001). Compared to control rats, cardiac ADAM10- and MMP 9- protein expressions increased by 20 times, and active/total MMP 9 proteolytic activity showed increase tendency at day 14 after cessation of DOX injection (n=10, each group). DOX-treated $H_9C_2$ cell showed increased ADAM10 protein expression with dose-dependency (p<0.01) and morphometric changes showed the increase of ventricular interstitial, nonvascular collagen deposition. These data suggest that activation of cardiac peroxynitrite with increased iNOS expression and ADAM 10-dependent MMP 9 expression may be a molecular mechanism that contributes to left ventricular remodeling in DOXinduced cardiomyopathy.

• 한국임상수의학회지
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• 제34권5호
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• pp.353-355
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• 2017

A four month old, intact female Jindo dog presented to the Veterinary Teaching Hospital of Kangwon National University with collapse. Physical examination revealed a heart rate of more than 200 beats per minute. Blood tests showed mild anemia and mild neutrophilia, while thoracic radiography and ultrasonography revealed no remarkable findings. Electrocardiography showed ventricular premature complexes (VPCs). The dog was diagnosed with congenital ventricular tachyarrhythmia. The condition was improved by lidocaine infusion. After 10 days, the dog was discharged from the hospital with a prescription of atenolol, pimobendan, diltiazem, furosemide, spironolactone, and L-carnitine. This dog is still alive after 31 months. However, progressive cardiac remodeling was confirmed on radiography and ultrasonography. Congenital ventricular tachyarrhythmia is rare in dogs, and the prognosis of reported cases is poor. This report describes the long-term successful management of a dog with congenital ventricular tachyarrhythmia.

• Journal of Chest Surgery
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• 제39권9호
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• pp.659-667
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• 2006

배경: 저산소증, 공기색전증, monocrotaline 약물 주입 등에 의해 혈관 내막의 손상을 일으켜 폐동맥내세포외간질 단백질 합성을 활성화시키고 혈관의 중막비후나 신생내막의 형성을 일으키는 혈관개조(vascular remodeling) 실험이 활발하게 진행되고 있다. 본 연구는 폐정맥을 폐쇄시킨 후 변화된 혈류에 의해 폐장이 어떻게 반응하는지 확인하고자 동물실험을 실시하였다. 대상 및 방법: $352{\pm}18g$의 흰쥐(n=10)를 이용하여 ketamine 근육내 주사로 마취하여 정중흉골절개술을 시행하고 심장을 노출시킨 후 우측 폐정맥을 크립을 이용하여 폐쇄하였으며, 15일 후 폐동맥압, 좌심실과 심실중격 대비 우심실 무게비(RV/LV+Sweight ratio), 말초 폐동맥의 외측지름대비 벽두께비(percent wall thickness (%WT)) 등을 측정하여 대조군(n=5)과 비교하였다. 결과: 폐정맥 폐쇄군의 폐동맥압은 38{\pm}12 mmHg로 대조군의 $13{\pm}4mmHg$에 비해 의의 있게 증가되었다(p<0.05). 좌심실과 심실중격 대비 우심실 무게비는 대조군의 $0.35{\pm}0.04$에 비해 $0.52{\pm}0.07$로 통계적으로 유의한 우심실 비대 소견을 보였고(p<0.05), 말초 폐동맥의 외측지름대비 벽두께비는 폐쇄군이 $22.4{\pm}6.7%$로 대조군의 $6.7{\pm}3.4%$에 비해 증가되었다(p<0.05). 결론: 한쪽 폐의 폐정맥 폐쇄는 폐동맥고혈압, 우심실 비대, 말초 폐동맥의 중막 비후 소견을 유도하였다. 이는 폐동맥 혈관개조의 병리학적 특성을 나타내는 것으로 일측 폐정맥을 폐쇄하는 경우 반대측 폐장의 폐혈류량 증가뿐만 아니라 혈관개조를 유발하는 내막의 손상을 동반함을 알 수 있었다.

• Clinical and Experimental Pediatrics
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• 제56권3호
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• pp.101-106
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• 2013

Despite developments in surgical techniques and other interventions, right ventricular (RV) failure remains an important clinical problem in several congenital heart diseases (CHD). RV function is one of the most important predictors of mortality and morbidity in patients with CHD. RV failure is a progressive disorder that begins with myocardial injury or stress, neurohormonal activation, cytokine activation, altered gene expression, and ventricular remodeling. Pressure-overload RV failure caused by RV outflow tract obstruction after total correction of tetralogy of Fallot, pulmonary stenosis, atrial switch operation for transposition of the great arteries, congenitally corrected transposition of the great arteries, and systemic RV failure after the Fontan operation. Volume-overload RV failure may be caused by atrial septal defect, pulmonary regurgitation, or tricuspid regurgitation. Although the measurement of RV function is difficult because of many reasons, the right ventricle can be evaluated using both imaging and functional modalities. In clinical practice, echocardiography is the primary mode for the evaluation of RV structure and function. Cardiac magnetic resonance imaging is increasingly used for evaluating RV structure and function. A comprehensive evaluation of RV function may lead to early and optimal management of RV failure in patients with CHD.

• Clinical and Experimental Pediatrics
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• 제60권11호
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• pp.365-372
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• 2017

Purpose: The mechanism for the pathogenesis of adriamycin (ADR)-induced cardiomyopathy is not yet known. Different hypotheses include the production of free radicals, an interaction between ADR and nuclear components, and a disruption in cardiac-specific gene expression. Apoptosis has also been proposed as being involved in cardiac dysfunction. The purpose of this study was to determine if apoptosis might play a role in ADR-induced cardiomyopathy. Methods: Male Sprague-Dawley rats were separated into 2 groups: the control group (C group) and the experimental group (ADR 5 mg/wk for 3 weeks through intraperitoneal injections; A group). Echocardiographic images were obtained at week 3. Changes in caspase-3, B-cell leukemia/lymphoma (Bcl)-2, Bcl-2-associated X (Bax), interleukin (IL)-6, tumor necrosis $factor-{\alpha}$, brain natriuretic peptide (BNP), troponin I, collagen 1, and collagen 3 protein expression from the left ventricle tissues of C and A group rats were determined by Western blot. Results: Ascites and heart failure as well as left ventricular hypertrophy were noted in the A group. Ejection fraction and shortening fraction were significantly lower in the A group by echocardiography. The expression of caspase-3, Bax, IL-6, BNP, collagen 1, and collagen 3 were significantly higher in the A group as compared with the C group. Protein expression of Bcl-2 decreased significantly in the A group compared with the C group. Conclusion: ADR induced an upregulation of caspase-3, Bax, IL-6, and collagen, as well as a depression in Bcl-2. Thus, apoptosis and fibrosis may play an important role in ADR-induced cardiomyopathy.

• Journal of Chest Surgery
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• 제56권5호
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• pp.295-303
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• 2023

Background: The use of Adriamycin (ADR), also known as doxorubicin, as a chemotherapy agent is limited by its detrimental adverse effects, especially cardiotoxicity. Recent studies have emphasized the crucial role of angiotensin II (Ang-II) in the development of ADR-induced cardiomyopathy. This study aimed to explore the potential cardioprotective effects of losartan in a rat model of ADR-induced cardiomyopathy. Methods: Male Sprague-Dawley rats were randomly divided into 3 groups: a control group (group C), an ADR-treated group (ADR 5 mg/kg/wk for 3 weeks via intraperitoneal injections; group A), and co-treatment of ADR with losartan group (same dose of ADR and losartan; 10 mg/kg/day per oral for 3 weeks; group L). Western blot analysis was conducted to demonstrate changes in brain natriuretic peptide, collagen 1, tumor necrosis factor (TNF)-α, interleukin-6, matrix metalloproteinase (MMP)-2, B-cell leukemia/lymphoma (Bcl)-2, Bcl-2-associated X (Bax), and caspase-3 protein expression levels in left ventricular (LV) tissues from each group. Results: Losartan administration reduced LV hypertrophy, collagen content, and the expression of pro-inflammatory factors TNF-α and MMP-2 in LV tissue. In addition, losartan led to a decrease in the expression of the pro-apoptotic proteins Bax and caspase-3 and an increase in the expression of the anti-apoptotic protein Bcl-2. Moreover, losartan treatment induced a reduction in the apoptotic area compared to group A. Conclusion: In an ADR-induced cardiomyopathy rat model, co-administration of ADR with losartan presented cardioprotective effects by attenuating LV hypertrophy, pro-inflammatory factors, and apoptosis in LV tissue.

• 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.

• 대한핵의학회지
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• 제34권1호
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• pp.30-38
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• 2000

목적: 심근의 생존능을 평가하기 위해 보편적으로 재관류술 전에 시행하는 심근관류 SPECT에 의한 관류지수를 평가함으로써 좌심실의 재구도 즉 좌심실 확장을 미리 예측할 수 있는 지와 또한 재관류술이 재구도를 예방하는데 도움이 되는지를 알아보고자 하였다. 대상 및 방법: 급성심근경색이 진단되어 혈전용해제 치료를 받은 7명과 치료하지 않은 9명으로 입원 후 $2{\sim}9$일 이내에 심근관류 영상을 시행한 16명의 환자를 대상으로 하였다. 모든 심근관류영상은 관동맥확장술과 관동맥우회로술과 같은 재관류술 시행 전에 시행하였다. 모든 환자는 심근경색 1주내에 초기 심초음파를 경색후 평균 $6.7{\pm}4.7$개월에 추적 심초음파를 시행하였다. 좌심실의 용적은 Simpson 방법을 이용하여 심첨부 4방에서 확장기 말과 수축기 말에 좌심실용적을 구하였다. 좌심실 벽운동은 심근관류 SPECT와 같이 16분절로 나누었으며 운동이상의 정도를 4단계로 나누어 평가하였다. 각 환자의 관류와 벽운동 장애의 점수의 총합을 16분절로 나누어 관류와 벽운동지수를 구하였다. 경색초기의 좌심실용적과 비교하여 추적 검사시에 좌심실의 용적이 10% 이상 증가한 군(A군, n=8)과 용적이 감소하거나 10% 미만 증가된군(B군, n=8)의 두 군으로 인위적으로 나누었다. 두 군간에 경색초기의 좌심실의 벽운동지수, Q파 여부, 재관류술여부, CKMB 수치, 관류지수, 초기 좌심실용적 및 좌심실 구혈률 등을 비교하였다. 좌심실 용적의 확장 유무 및 좌심실 용적의 변화량과 부하기-휴식기 관류지수, 벽운동지수, 초기 좌심실용적, Q파 여부, 재관류술 여부, CKMB 수치 그리고 좌심실 구혈률 등의 관계를 다변량로짓 분석을 시행하여 분석하였다. 또한 좌심실 확장정도와 여러 변수와의 관계를 다변량선형 분석을 통해 분석하였다. 결과: 좌심실 용적의 증가와 벽운동지수, 관류지수, CKMB수치, 재관류술여부, Q파 유무, 좌심실 구혈률과의 관계를 좌심실의 용적이 증가된군(A군)과 증가되지 않은 군(B군)으로 나누어 평가하였다. 좌심실 용적의 증가여부에 따른 차이를 보았을 때 휴식시의 관류지수는 용적이 증가한 군에서 유의한 차이로 의미 있는 감소를 보였다. 그러나 이외 인자들은 양군간에 차이가 없었다. 좌심실 용적의 증가와 재관류술 여부와의 관계: 좌심실 확장을 보인 8명의 환자 중 3명은 재관류술을 시행하지 않았으며 이 들 3명 모두에서 좌심실 용적의 확장을 보였다. 또한 재관류술을 시행한 13명의 환자 중 5명(38%)은 좌심실 용적의 확장을 보였다. 좌심실 용적의 증가와 경색위치와의 관계: 전벽 경색 10명 중 4명, 하벽 경색 5명 중 3명, 그리고 측벽 경색을 보인 1명에서 용적 확장소견을 보였다. 좌심실 용적의 확장유무 및 확장정도와 부하 및 휴식기 관류지수, 초기 좌심실 용적, CKMB수치, Q파 유무, 벽운동지수, 심실 구혈률, 재관류술 여부에 따른 다변량분석: 용적 증가량을 비독립변수로 하여 다중회귀선형분석에서 경색초기에 평가한 휴식시의 관류지수만이 좌심실용적 변화량에 대해 유의한 예측인자로 나타났다. 그러나 이외의 모든 인자들은 유의한 예측인자로 작용하지 못하였다. 또한 좌심실 용적의 증가량을 10% 이상 증가 여부를 비독립 변수로 한 다중회귀로짓분석에서는 휴식시의 관류지수와 재관류술 여부가 유의한 예측인자로 나타났다. 결론: 급성 심근경색 초기에 실시한 심근관류 SPECT 검사상 좌심실 확장군과 비확장군은 유의한 휴식기 관류지수의 차이를 보였고 또한 다변량분석에서 휴식기의 관류지수는 좌심실 확장을 예측할 수 있는 유일한 지표였다. 또한 작은 수의 증례이지만 경색관련 동맥의 재관류술은 좌심실 확장을 감소시킬 수 있는 하나의 방법으로 보인다.

• 한국가시화정보학회지
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• 제16권2호
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• pp.31-37
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• 2018

Ischemic mitral regurgitation (IMR) is the primary mitral valve (MV) pathology in the aftermath of myocardial infarction as a consequence of regional left ventricular (LV) remodeling. We investigated the effect of asymmetric papillary muscle (PM) displacement and annular dilation on IMR development. Virtual MV modeling was performed to create a normal human MV. Asymmetric PM displacement, asymmetric annular dilation, and the combination of these two pathologic characteristics were modeled. Dynamic finite element evaluation of MV function was performed across the complete cardiac cycle for the normal and three different IMR MV models. While the normal MV demonstrated complete leaflet coaptation, each pathologic MV model clearly revealed deteriorated leaflet coaptation and abnormal stress distributions. The pathologic MV model having both asymmetric PM displacement and annular dilation showed the worst leaflet malcoaptation. Simulation-based biomechanical evaluation of post-ischemic LV remodeling provides an excellent tool to better understand the pathophysiologic mechanism of IMR development.

• 한국임상수의학회지
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• 제31권5호
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• pp.403-406
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• 2014

임상증상이 없는 6년령의 3.1 kg 말티즈견이 심잡음의 원인에 대한 추가 검진을 위해서 내원하였다. 흉부 방사선에서는 우심비대가 확인되었다. 심장 초음파에서는 두드러진 우심실비대, 비정상적 근육 다발과 섬유성 결절이 우심실 유출로 아래 누두부에서 발견되었다. 이러한 소견은 우심실양분증의 전형적인 형태학적 소견이다. 비정상 근육다발에서 주폐동맥으로 향하는 와류의 속도는 4.6 m/sec, 삼첨판 역류는 4.4 m/sec, 주폐동맥 혈류는 1.1 m/sec로 각각 측정되었다. 본 환자는 비록 임상증상은 없지만 협착에 의한 과도한 후부하와 그로 인한 심장의 손상을 막기 위해서 현재 atenolol (0.5 mg/kg) 을 복용하고 있다. 본 증례는 한국에서 발생한 견종에서 매우 드문 우심실양분증에 대해서 기술하였습니다.