चूहे में वाम पूर्वकाल अवरोही कोरोनरी धमनी के स्थायी Ligation: पोस्ट-रोधगलन पुनर्गठन और दिल की विफलता का एक मॉडल
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
दिल की विफलता दिल आराम में या तनाव के दौरान सेलुलर ऑक्सीजन आवश्यकताओं के अनुरूप दर से रक्त पंप करने में विफल रहता है, जिसमें एक सिंड्रोम है। यह परिश्रम पर विशेष रूप से तरल पदार्थ प्रतिधारण, सांस की तकलीफ, और थकान, की विशेषता है। दिल की विफलता एक से बढ़ सार्वजनिक स्वास्थ्य समस्या है, अस्पताल में भर्ती का प्रमुख कारण है, और मृत्यु दर का एक प्रमुख कारण है। इस्कीमिक हृदय रोग दिल की विफलता का मुख्य कारण है।
वेंट्रिकुलर remodeling के बाएं वेंट्रिकल की संरचना, आकार, और आकार में परिवर्तन को दर्शाता है। बाएं वेंट्रिकल की यह वास्तु remodeling के (जैसे, प्रणालीगत धमनी उच्च रक्तचाप या महाधमनी एक प्रकार का रोग), या मात्रा अधिभार द्वारा दबाव अधिभार से, चोट (जैसे, रोधगलन) से प्रेरित है। वेंट्रिकुलर remodeling के दीवार तनाव को प्रभावित करता है, यह हृदय समारोह पर और दिल की विफलता के विकास पर गहरा प्रभाव पड़ता है। बाईं पूर्वकाल descendin की स्थायी बंधाव का एक मॉडलचूहों में जी कोरोनरी धमनी वेंट्रिकुलर remodeling और हृदय समारोह के बाद रोधगलन जांच करने के लिए प्रयोग किया जाता है। इस मॉडल को कोरोनरी धमनी उतरते बाईं पूर्वकाल के क्षणिक बंधाव के मॉडल की तुलना में उद्देश्यों और pathophysiological प्रासंगिकता के संदर्भ में मौलिक रूप से अलग है। Ischemia / reperfusion की चोट के बाद इस मॉडल में, रोधगलितांश की प्रारंभिक हद reperfusion की निम्नलिखित दौरे निस्तारण को प्रभावित करने वाले कारकों द्वारा संग्राहक जा सकता है। इसके विपरीत, कोरोनरी धमनी उतरते बाईं पूर्वकाल की स्थायी बंधाव के बाद 24 घंटे में रोधगलितांश क्षेत्र तय हो गई है। इस मॉडल में हृदय समारोह 1) रोधगलितांश विस्तार, रोधगलितांश चिकित्सा, और निशान गठन की प्रक्रिया से प्रभावित हो जाएगा; और 2) बाएं निलय फैलने, हृदय अतिवृद्धि, और वेंट्रिकुलर remodeling के सहवर्ती विकास।
कोरोनरी धमनी, आक्रामक hemodynamic विदेश मंत्रालय की तकनीक उतरते बाईं पूर्वकाल की स्थायी बंधाव के मॉडल के अलावाचूहों में surements विस्तार से प्रस्तुत किया है।
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
दौरे संरचना और समारोह में लगातार परिवर्तन, दिल की विफलता के लिए बाएं निलय में शिथिलता के विकास, और प्रगति के कई murine मॉडल 12 में जांच की जा सकती है। कार्डिएक remodeling और शिथिलता दौरे चोट से प्रेरित या दबाव से…
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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