마우스의 왼쪽 전방 내림차순 관상 동맥의 영구 결찰 : 심근 경색 리모델링과 심장 마비의 모델
Summary
Heart failure is the leading cause of hospitalization and a major cause of mortality. A model of permanent ligation of the left anterior descending coronary artery in mice is applied to investigate ventricular remodelling and cardiac dysfunction post-myocardial infarction. The technique of invasive hemodynamic measurements in mice is presented.
Abstract
심장 마비는 심장이 휴식 또는 스트레스 동안 세포 산소 요구에 상응하는 속도로 혈액을 펌프에 실패하는 증후군이다. 그것은 노력에 특히 체액 저류, 호흡 곤란, 피로, 특징입니다. 심장 마비는 성장 공중 보건 문제, 입원의 주요 원인 및 사망의 주요 원인이다. 허혈성 심장 질환이 심장 기능 상실의 주요 원인이다.
심실 리모델링 좌심실의 구조, 크기 및 형태의 변화를 의미한다. 좌심실이 구조적 리모델링 (예, 전신 동맥 고혈압 또는 대동맥판 협착증), 또는 볼륨과 부하 압력 과부하에 의해 부상 (예를 들면, 심근 경색)에 의해 유도된다. 심실 벽 리모델링 응력에 영향을 받기 때문에, 이는 심장 기능에 심부전의 발전에 지대한 영향을 미친다. 왼쪽 전방 descendin의 영구 결찰 모델마우스에서 g 관상 동맥은 심실 리모델링과 심장 기능 심근 경색을 조사하는 데 사용됩니다. 이 모델은 관상 좌전 하행의 과도 결찰 모델의 비교 목적 및 병태 생리 학적 관련성의 관점에서 근본적으로 다르다. 허혈 / 재관류 손상의 후자의 모델에서 초기 경색의 정도는 재관류 심근 회수에 영향을 미치는 인자에 의해 조절 될 수있다. 대조적으로, 관상 좌전 하행 영구적 결찰 후 24 시간에서 경색 부분은 고정되어있다. 이 모델에서 심장 기능은 1) 경색 확장, 경색 치유 및 흉터 형성의 과정에 의해 영향을 받는다; 2) 좌심실 팽창, 심장 비대, 심실 리모델링의 수반 개발.
관상 동맥, 침습적 혈역학 MEA의 기술 좌전 하행의 영구 결찰의 모델 외에마우스의 숏 상세하게 제시된다.
Introduction
Heart failure is a syndrome in which the heart fails to pump blood at a rate commensurate with the cellular oxygen requirements at rest or during stress. It is characterized by fluid retention, shortness of breath, and fatigue, in particular on exertion. Heart failure is a growing public health problem, the leading cause of hospitalization, and a major cause of mortality. Ischemic heart disease is the main cause of heart failure1.
Ventricular remodelling refers to changes in structure, size, and shape of the left ventricle. In other words, ventricular remodelling concerns an alteration of the left ventricular architecture. This architectural remodelling of the left ventricle is induced by injury (e.g., myocardial infarction), by pressure overload (e.g., systemic arterial hypertension or aortic stenosis), or by volume overload (e.g., mitral insufficiency). Since ventricular remodelling affects wall stress, it has a profound impact on cardiac function and on the development of heart failure.
Loss of myocardial tissue following acute myocardial infarction results in a decreased systolic ejection and an increased left ventricular end-diastolic volume and pressure. The Frank-Starling mechanism, implying that an increased end-diastolic volume results in an increased pressure developed during systole, may help to restore cardiac output. However, the concomitant increased wall stress may induce regional hypertrophy in the non-infarcted segment, whereas in the infarcted area expansion and thinning may occur. Experimental animal studies show that the infarcted ventricle hypertrophies and that the degree of hypertrophy is dependent on the infarct size2.
The loss of myocardial tissue following acute myocardial infarction results in a sudden increase in loading conditions. Post-infarct remodelling occurs in the setting of volume overload, since the stretched and dilated infarcted tissue increases the left ventricular volume. An increased ventricular volume not only implies increased preload (passive ventricular wall stress at the end of diastole) but also increased afterload (total myocardial wall stress during systolic ejection). Afterload is increased since the systolic radius is increased. Therefore, ventricular remodelling post-myocardial infarction is characterized by mixed features of volume overload and pressure overload.
The myocardium consists of 3 integrated components: cardiomyocytes, extracellular matrix, and the capillary microcirculation. All 3 components are involved in the remodelling process. Matrix metalloproteinases produced by inflammatory cells induce degradation of intermyocyte collagen struts and cardiomyocyte slippage. This leads to infarct expansion characterized by the disproportionate thinning and dilatation of the infarct segment3. In later stages of remodelling, interstitial fibrosis is induced, which negatively affects the diastolic properties of the heart.
The vascular and cardiomyocyte compartment in the myocardium should remain balanced in the process of ventricular remodelling to avoid tissue hypoxia4,5. Whether hypertrophy progresses to heart failure or not may be critically dependent on this balance between the vascular and cardiomyocyte compartment in the myocardium.
A model of permanent ligation of the left anterior descending coronary artery in mice is used to investigate ventricular remodelling and cardiac function post-myocardial infarction. This model is fundamentally different in terms of objectives and pathophysiological relevance compared to the model of transient ligation of the left anterior descending coronary artery. In this latter model of ischemia/reperfusion injury, the initial extent of the infarct may be modulated by factors that affect myocardial salvage following reperfusion6. In contrast, the infarct area at 24 hours after permanent ligation of the left anterior descending coronary artery is fixed. Cardiac function in this model will be affected by 1) the process of infarct expansion, infarct healing, and scar formation; and 2) the concomitant development of left ventricular dilatation, cardiac hypertrophy, and ventricular remodelling.
Protocol
Representative Results
Discussion
심근 구조 및 기능의 변화는 만성 심부전에 좌심실 기능 장애의 개발, 진행은 여러 뮤린 모델 (12)에 조사 될 수있다. 심장 리모델링 및 기능 장애는 심근 손상에 의해 유발 또는 압력에 의해 대동맥 수축을 횡단하는 보조 과부하, 또는 팽창 심근 병증 (12)의 유전 적 모델에서 조사 할 수있다 할 수있다. 물론, 쥐 모델의 가장 뚜렷한 장점은 형질 전환 및 세포 형 특정 및 유도 유전자 …
Divulgations
The authors have nothing to disclose.
Acknowledgements
This work was supported by Onderzoekstoelagen grant OT/13/090 of the KU Leuven and by grant G0A3114N of the FWO-Vlaanderen.
Materials
| Reagents | |||
| Buprenorphine (Buprenex®) | Bedford Laboratories | ||
| Sodium Pentobarbital (Nembutal®) | Ceva | ||
| Betadine® | VWR internationals | 200065-400 | |
| 5 – 0 silk suture | Ethicon, Johnson & Johnson Medical | K890H | |
| 6 – 0 prolene suture | Ethicon, Johnson & Johnson Medical | F1832 | |
| 6 – 0 Ti- Cron suture | Ethicon, Johnson & Johnson Medical | F1823 | |
| Urethane | Sigma | 94300 | |
| Alconox | Alconox Inc. | ||
| Equipment | |||
| Ventilator, MiniVent Model 845 | Hugo Sachs | 73-0043 | |
| Chest retractor or Thorax retractor | Kent Scientific corporation | INS600240 | ALM Self-retaining, serrated, 7cm long, 4 x 4 "L" shaped prongs, 3mm x 3mm |
| 1.0 French Millar pressure catheter | Millar Instruments | SPR – 1000/NR | |
| Powerlab | ADInstruments Pty Ltd. | ||
| LabChart® software | ADInstruments Pty Ltd. | ||
| Rectal probe | ADInstruments Pty Ltd. |
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