Farelerde Sol Ön İnen Koroner Arter Daimi ligasyonu: Post-miyokard Enfarktüs Remodelling ve Kalp Yetmezliği Bir Model
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
Kalp yetmezliği, kalp istirahat veya stres sırasında hücresel oksijen gereksinimleri ile orantılı bir hızda kan pompalamak için başarısız olan bir sendromdur. Bu efor özellikle sıvı retansiyonu, nefes darlığı, yorgunluk ve, ile karakterizedir. Kalp yetmezliği büyüyen bir halk sağlığı sorunu, hastaneye önde gelen nedenidir ve mortalitenin önemli bir nedenidir. İskemik kalp hastalığı, kalp yetmezliği ana nedenidir.
Sol ventriküler yeniden modellenme ventrikül yapısı, boyut ve şekil değişiklikleri ifade eder. Sol ventrikül Bu mimari biçimlenme (örneğin, sistemik arteriyel hipertansiyon veya aort darlığı), ya da volüm ile basınç yükü ile, yaralanma (örneğin, miyokard infarktüsü) tarafından uyarılır. Ventrikül yeniden şekillenme duvar stresi etkilediği için, kardiyak fonksiyonu ve kalp yetmezliği gelişimi üzerinde derin bir etkisi vardır. Sol ön descendin sürekli bağlanmasından bir modeliFarelerde g koroner arter ventriküler yeniden modellenme ve kardiyak fonksiyon post-miyokardiyal enfarktüs incelemek için kullanılmıştır. Bu model koroner arter sol ön inen geçici ligasyonu modeline kıyasla hedefleri ve patofizyolojik alaka açısından temelde farklıdır. Iskemi / reperfüzyon hasarının, bu ikinci modelde, enfarktüs ilk ölçüde reperfüzyonda miyokardiyal kurtarma etkileyen faktörler tarafından modüle edilebilir. Buna karşılık, koroner arter sol ön inen kalıcı ligasyonu 24 saat sonra enfarktüs alanı sabittir. Bu modelde kardiyak fonksiyon 1) enfarktüs genişleme, enfarktüs şifa ve skar oluşumu süreci etkilenecektir; ve 2), sol ventrikül dilatasyonu, kalp hipertrofisi, ve ventriküler yeniden eşlik eden gelişme.
Koroner arter, invaziv hemodinamik mea tekniği sol ön inen kalıcı ligasyonu modeli yanındaFarelerde ümler ayrıntılı olarak sunulmuştur.
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
Miyokard yapısı ve fonksiyonu Kronik değişiklikler, kalp yetmezliği, sol ventrikül disfonksiyonu gelişimi, ilerlemesi ve çeşitli kemirgen modellerinde 12 incelenebilir. Kardiyak biçimlenme ve disfonksiyonu miyokard hasarı ile uyarılan ya da basınç aort daralma enine ikincil aşırı yüklemeyin veya dilate kardiyomiyopati 12 genetik modellerinde araştırılması olabilir olabilir. Açıkçası, kemirgen modellerinin en belirgin faydası transgenik ve hücre tipi özel ve uyarılabili…
Divulgazioni
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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