1. بروتوكول النص <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> قبل الشروع في عملية جراحية، تخدير ماوس الذكور (C57BL / 6) وهذا هو 6 أسابيع من العمر أو أكثر عن طريق الاستنشاق من 2-5٪ isoflurane. أداء قليل أخمص القدمين للتأكد من أن الحيوان هو تخدير بما فيه الكفاية. </li><li style=";text-align:right;direction:rtl"> يتم وضع الماوس على ظهرها وعيه على وسادة دافئة للحفاظ على درجة حرارة ثابتة للC. ° 37 وحلق الصدر بركي على الجانب الأيسر. </li><li style=";text-align:right;direction:rtl"> تأمين الماوس لجهاز التنبيب مع دائرة isoflurane شغلها. إدخال أنبوب من 0.2 القطر الداخلي في القصبة الهوائية الماوس من خلال الفم، ثم ضع الماوس المنببين على مساحة جراحي العقيم (37 ° C بواسطة وحدة تحكم بدرجة الحرارة) وتوصيل أنبوب القصبة الهوائية لجهاز التنفس الصناعي (معدل 120 في دقيقة، ضغط من 4-6 MMH 2 O)؛ تطهير المنطقة مع betadine والايثانول 75٪. </li><li style=";text-align:right;direction:rtl"> تطبيق مرهم للعين للعيون الفأر. وضع معيار أقطاب ECG على الكفوف وتوصيل الماوس إلى مسجل ECG. </li&gt; <li style=";text-align:right;direction:rtl"> استخدام مقص العقيمة لجعل شق الطول 1،5 على طول خط منتصف الإبط. وتستخدم بدلا من المقص مشرط لتجنب إصابة الأنسجة الكامنة في الفئران. ثم، استخدم مقص سفينة حادة معلومات سرية لتشريح العضلات وسحب بركي من جدار الصدر. </li><li style=";text-align:right;direction:rtl"> إجراء بضع الصدر بين الأضلاع اليسرى الثالث والرابع لتصور سطح الأمامي للقلب والرئة اليسرى </li><li style=";text-align:right;direction:rtl"> سحب المزيد من الجدار الصدري باستخدام مبعاد مناسبة من أجل تحسين التصور وسهولة الوصول إليها. إزالة التأمور ملقط مسنن باستخدام مقص حادة وذات الرؤوس. </li><li style=";text-align:right;direction:rtl"> Ligate التاجي الأيسر الشريان عن طريق وضع إبرة (المرفقة مع خياطة ethilon 7-0) تحت الشريان مع عصابة من عضلة القلب بين ضمد والشريان. يتم التحقق من وانسداد الشريان التاجي ناجحة من نقص الحراك / تعذر الحركة للجدار البطين الأيسر الأمامي والتعديلات على تسجيل ECG (مثل ارتفاع الجزء ST، QRS broadeniنانوغرام) </li><li style=";text-align:right;direction:rtl"> إغلاق الصدر بوضع اثنين غرز (6-0 ethilon خياطة) على الأضلاع الثالث والرابع. </li><li style=";text-align:right;direction:rtl"> استخدام 5-0 خياطة ethilon لإغلاق الجلد. </li><li style=";text-align:right;direction:rtl"> لتسكين بعد العملية، إدارة حقنة واحدة داخل الصفاق من البوبرينورفين (0.05 مغ / كغ). فإن الحيوانات استرداد تلقائيا خلال 2-5 دقيقة بعد وقف التخدير isoflurane. وأخيرا، ضع الماوس في قفص دافئة وتوفير 0.6 ملغ / مل من البوبرينورفين في مياه الشرب (تراكب النص: 0.6 ملغ / مل في مياه الشرب) لمنع استغاثة بعد الجراحة. يرصد عن كثب الماوس لال 24 ساعة الأولى بعد الجراحة. </li><li style=";text-align:right;direction:rtl"> يتم تنفيذ تخطيط صدى القلب لتقييم وظائف القلب بعد 3 أيام احتشاء عضلة القلب. يتم التحقق الداخلي الناجحة التي قام بها تعذر الحركة في جدار البطين الأيسر الأمامي (انظر الفيديو المرفق في النتائج). في نهاية التجربة، سيتم جمعها وتخزينها قلب في 80oC لاستكمال التحقيقات. أي التعبير الجيني. </li></ol>

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	<li>Tabrizchi, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Beta-blocker+therapy+after+acute+myocardial+infarction.">Beta-blocker therapy after acute myocardial infarction.</a> Expert Rev. Cardiovasc. Ther. 11, 293-296 (2013).</li><li>Pell, S., Fayerweather, W. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Trends+in+the+incidence+of+myocardial+infarction+and+in+associated+mortality+and+morbidity+in+a+large+employed+population,+1957-1983.">Trends in the incidence of myocardial infarction and in associated mortality and morbidity in a large employed population, 1957-1983.</a> N. Engl. J. 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J., Flegal, K., O'Donnell, C., Kittner, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Heart+disease+and+stroke+statistics--2006+update:+A+report+from+the+american+heart+association+statistics+committee+and+stroke+statistics+subcommittee.">Heart disease and stroke statistics--2006 update: A report from the american heart association statistics committee and stroke statistics subcommittee.</a> Circulation. 113, 85-151 (2006).</li><li>van den Bos, E. J., Mees, B. M., de Waard, M. C., de Crom, R., Duncker, D. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+novel+model+of+cryoinjury-induced+myocardial+infarction+in+the+mouse:+A+comparison+with+coronary+artery+ligation.">A novel model of cryoinjury-induced myocardial infarction in the mouse: A comparison with coronary artery ligation.</a> Am. J. Physiol. Heart Circ. Physiol. 289, 1291-1300 (2005).</li><li>Omerovic, E., Ramunddal, T., Lorentzon, M., Nordlander, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+neuropeptide+y2+receptor+blockade+on+ventricular+arrhythmias+in+rats+with+acute+myocardial+infarction.">Effects of neuropeptide y2 receptor blockade on ventricular arrhythmias in rats with acute myocardial infarction.</a> Eur. J. Pharmacol. 565, 138-143 (2007).</li><li>Ahn, D., Cheng, L., Moon, C., Spurgeon, H., Lakatta, E. G., Talan, M. 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Card Fail. 14, 161-166 (2008).</li><li>Omerovic, E., Bollano, E., Basetti, M., Kujacic, V., Waagstein, L., Hjalmarson, A., Waagstein, F., Soussi, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Bioenergetic,+functional+and+morphological+consequences+of+postinfarct+cardiac+remodeling+in+the+rat.">Bioenergetic, functional and morphological consequences of postinfarct cardiac remodeling in the rat.</a> J. Mol. Cell. Cardiol. 31, 1685-1695 (1999).</li><li>Gao, E., Lei, Y. H., Shang, X., Huang, Z. M., Zuo, L., Boucher, M., Fan, Q., Chuprun, J. K., Ma, X. L., Koch, W. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+novel+and+efficient+model+of+coronary+artery+ligation+and+myocardial+infarction+in+the+mouse.">A novel and efficient model of coronary artery ligation and myocardial infarction in the mouse.</a> Circ. Res. 107, 1445-1453 (2010).</li></ol>

الإعلان عن أي تضارب في المصالح.

العملية الجراحية لربط المخصص كما هو موضح في هذا التقرير هو وسيلة يمكن الاعتماد عليها وقابلة للتكرار لتحريض MI التجريبية في الفئران 3 و 6. وربط المخصص للوفقا لهذا البروتوكول يدفع نقص تروية عضلة القلب عادة الانخراط ~ 40٪ من البطين الأيسر 3. هذا يدفع تغييرات مهمة في قطاع ST ECG 7 و شحوب مرئية على سطح الأمامي للقلب. بسبب احتشاء عضلة القلب وكبيرة، يمكن أن تكون وفيات تصل إلى 30٪ 8 و 9. وينبغي بذل علما بأن معدل وفيات المنطقة واحتشاء آخر MI-عضلة القلب قد تكون مختلفة بين سلالات الحيوانية المختلفة. طريقة ديها العديد من المزايا. وضع شق الجلد على طول خط منتصف الإبط بدلا من جدار الصدر الأمامي على تسهيل التحقيق في وقت لاحق مع ضربات القلب. وغرز في الجرح المنطوق لا تتداخل مع التصوير بالموجات فوق الصوتية للقطاعات الأمامية للقلب. وعلاوة على ذلك، فإن التنبيب من الفئران يسمح للمشغلما يكفي من الوقت لإجراء الجراحة. وربط المخصص لل&quot;في الموقع&quot; داخل الصدر هو أكثر &quot;الفسيولوجية&quot; بدلا من ربط للLCA بعد تخريج من حيث سيؤدي ذلك إلى بطء شديد وحمل نقص الأكسجة العالمية 10. يحمل هذا النهج أيضا المزايا على النهج القائم على cryoinjury يرتبط هذا الأخير مع العمليات الفيزيولوجية المرضية تختلف عن نقص التروية الناجم عن احتشاء عضلة القلب التي قد تؤدي إلى تشويش الدراسات الآلي من اعتلال عضلة القلب الإقفاري. ونحن نعتقد أن هذا الفيديو والتعليمات المرفقة سيكون من تكملة مفيدة للتقنيات القائمة لMI التجريبية في الفئران. استكشاف الأخطاء وإصلاحها: <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> للحصول على أفضل رؤية الهياكل التشريحية الهامة (الأذين الأيسر، البطين الأيسر الأمامي الجدار، والرئة اليسرى)، وعادة ما يتم إجراء بضع الصدر الأيسر بين الثالث والضلع الرابع. </li><li style=";text-align:right;direction:rtl"> تكون على علم بأن عرضي ثقب من اليسار ATRالنتائج البوتاسيوم في نزيف حاد قد يؤدي إلى موت الحيوان. </li><li style=";text-align:right;direction:rtl"> وينبغي تجنب كدمة الرئة لأنه قد يسبب زيادة معدل الوفيات. إذا الرئة اليسرى والقلب بعد تغطية افتتاح الصدر، ينبغي سحب أنسجة الرئة بلطف باستخدام مثل القطن لاصقة. </li><li style=";text-align:right;direction:rtl"> وينبغي تجنب تركيز عال من isoflurane. عادة 2٪ من isoflurane هو الأمثل لتحقيق التخدير المناسب لعملية جراحية في الوقت الحاضر. </li></ol>

modified technique for coronary artery ligation in mice

احتشاء عضلة القلب (MI) هو واحد من أهم أسباب الوفيات في البشر 1-3. من أجل تحسين معدلات الاعتلال والوفيات في المرضى الذين يعانون من MI نحتاج معرفة أفضل حول الفيزيولوجيا المرضية لنقص تروية عضلة القلب. قد تكون هذه المعرفة قيمة لتحديد أهداف علاجية جديدة لعلاج القلب والأوعية الدموية مبتكرة 4. نموذج تجريبي MI في الفئران هو شعبية متزايدة الحيوانات الصغيرة في مجال البحوث قبل السريرية نموذج التي يسببها MI عن طريق ربط دائمة أو مؤقتة من الشريان التاجي الأيسر (LCA) 5. في هذا الفيديو، ونحن تصف طريقة خطوة بخطوة لكيفية حمل MI التجريبية في الفئران. الحيوان للتخدير الأولى مع 2٪ isoflurane. ومدخل أنبوب الماوس ثم فاقدا للوعي وصله بجهاز التنفس الصناعي للتهوية اصطناعية. وحلق الصدر الأيسر ويتم شق 1،5 سم على طول خط منتصف الإبط في الجلد. العضلة الصدرية الكبرى اليسار هو بصراحة dissociated حتى تتعرض الأضلاع. يتم سحبها طبقات العضلات جانبا وثابتة مع مبعاد-جفن. بعد هذه الاستعدادات، يتم تنفيذ بضع الصدر بين الأضلاع اليسرى الثالث والرابع من أجل رؤية سطح الأمامي للقلب والرئة اليسرى. وligated ثم الجزء القريب من الشريان LCA مع خياطة ethilon 7-0 الذي يدفع عادة حجم احتشاء ~ 40٪ من البطين الأيسر. في النهاية، يتم إغلاق الصدر والحيوانات تسكين بعد العملية الجراحية تلقي (Temgesic، 0.3 مل mg/50، والملكية الفكرية). يتم الاحتفاظ الحيوانات في قفص دافئ حتى الشفاء التلقائي.

<html><table border="1" style=";text-align:right;direction:rtl"><tbody><tr><td> صك </td><td> وصف وظيفة </td></tr><tr><td> معلومات سرية حادة مقص </td><td> تستخدم لقطع الجلد، وعضلات الصدر وربي، وخياطة الجروح </td></tr><tr><td> العين مبعاد </td><td> تستخدم للكشف عن رأي الجراحية </td></tr><tr><td> كليلة معلومات سرية ملقط </td><td> تستخدم لفهم الجلد والعضلات </td></tr><tr><td> إبرة حامل </td><td> عقد إبرة </td></tr><tr><td> 5-0 خياطة </td><td> خياطة الجلد تستخدم ل </td></tr><tr><td> 6-0 خياطة </td><td> تستخدم لخياطة عضلات الصدر </td></tr><tr><td> 7-0 خياطة </td><td> تستخدم لligate الشريان التاجي </td></tr></tbody></table> الجدول 1. الأدوات المستخدمة في إجراء احتشاء عضلة القلب. / ftp_upload/3093/3093figA.jpg &quot;/&gt; والرقم A. قبل ربط الشريان التاجي، ويتعرضون الأذين الأيسر، الرئة اليسرى، والجدار الأمامي للبطين الأيسر. كانت المجمعات QRS هو مبين في ECG ضيقة وقصيرة. <img alt="الرقم B" src="/files/ftp_upload/3093/3093figB.jpg" /> الرقم B. بعد ربط الشريان التاجي، الجدار الأمامي للبطين الأيسر وضعت زراق diskinesia. أصبحت المجمعات QRS أوسع بكثير وكان من الواضح أن قطاعات مرتفعة ST، مقارنة مع تلك قبل ربط الشريان التاجي.

Watch this Scientific Journal Video about Modified Technique for Coronary Artery Ligation in Mice at JoVE.com

Modified Technique for Coronary Artery Ligation in Mice

العملية الجراحية المستخدمة للحث على احتشاء عضلة القلب التجريبية في الفئران يبدأ بضع الصدر الأيسر بين الثالث والرابع في الأضلاع أجل رؤية سطح الأمامي للقلب والرئة اليسرى. وligated التاجي الأيسر الشريان، يتم إغلاق الصدر ويسمح الماوس لاسترداد تلقائيا.

تقنية لربط تعديل الشريان التاجي في الفئران

Myocardial infarction (MI) is one of the most important causes of mortality in humans1-3. In order to improve morbidity and mortality in patients with MI ...

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25.4K Views.  Sahlgrenska Academy, University of Gothenburg. العملية الجراحية المستخدمة للحث على احتشاء عضلة القلب التجريبية في الفئران يبدأ بضع الصدر الأيسر بين الثالث والرابع في الأضلاع أجل رؤية سطح الأمامي للقلب والرئة اليسرى. وligated التاجي الأيسر الشريان، يتم إغلاق الصدر ويسمح الماوس لاسترداد تلقائيا.

Video: Modified Technique for Coronary Artery Ligation in Mice

Use of a Hanging Weight System for Coronary Artery Occlusion in Mice

Murine studies of acute injury are an area of intense investigation, as knockout mice for different genes are becoming increasingly available 1-38. Cardioprotection by ischemic preconditioning (IP) remains an area of intense investigation. To further elucidate its molecular basis, the use of knockout mouse studies is particularly important 7, 14, 30, 39. Despite the fact that previous studies have already successfully performed cardiac ischemia and reperfusion in mice, this model is technically very challenging. Particularly, visual identification of the coronary artery, placement of the suture around the vessel and coronary occlusion by tying off the vessel with a supported knot is technically difficult. In addition, re-opening the knot for intermittent reperfusion of the coronary artery during IP without causing surgical trauma adds additional challenge. Moreover, if the knot is not tied down strong enough, inadvertent reperfusion due to imperfect occlusion of the coronary may affect the results. In fact, this can easily occur due to the movement of the beating heart.
Based on potential problems associated with using a knotted coronary occlusion system, we adopted a previously published model of chronic cardiomyopathy based on a hanging weight system for intermittent coronary artery occlusion during IP 39. In fact, coronary artery occlusion can thus be achieved without having to occlude the coronary by a knot. Moreover, reperfusion of the vessel can be easily achieved by supporting the hanging weights which are in a remote localization from cardiac tissues.
We tested this system systematically, including variation of ischemia and reperfusion times, preconditioning regiments, body temperature and genetic backgrounds39. In addition to infarct staining, we tested cardiac troponin I (cTnI)
as a marker of myocardial infarction in this model. In fact, plasma levels of cTnI correlated with infarct sizes (R2=0.8). Finally, we could show in several studies that this technique yields highly reproducible infarct sizes during murine IP and myocardial infarction6, 8, 30, 40, 41. Therefore, this technique may be helpful for researchers who pursue molecular mechanisms involved in cardioprotection by IP using a genetic approach in mice with targeted gene deletion. Further studies on cardiac IP using transgenic mice may consider this technique.

A murine model for myocardial ischemia and ischemic preconditioning is an important tool study cardioprotective mechanisms in vivo. Here, we report an easy applicable in situ model for cardiac IP using a hanging-weight system for coronary artery occlusion.

استخدام نظام وزن المعلقة لانسداد الشريان التاجي في الفئران

Murine studies of acute injury are an area of intense investigation, as knockout mice for different genes are becoming increasingly available 1-38. ...

Coronary Artery Ligation and Intramyocardial Injection in a Murine Model of Infarction

Mouse models are a valuable tool for studying acute injury and chronic remodeling of the myocardium in vivo. With the advent of genetic modifications to the whole organism or the myocardium and an array of biological and/or synthetic materials, there is great potential for any combination of these to assuage the extent of acute ischemic injury and impede the onset of heart failure pursuant to myocardial remodeling. 
Here we present the methods and materials used to reliably perform this microsurgery and the modifications involved for temporary (with reperfusion) or permanent coronary artery occlusion studies as well as intramyocardial injections. The effects on the heart that can be seen during the procedure and at the termination of the experiment in addition to histological evaluation will verify efficacy. 
Briefly, surgical preparation involves anesthetizing the mice, removing the fur on the chest, and then disinfecting the surgical area. Intratracheal intubation is achieved by transesophageal illumination using a fiber optic light. The tubing is then connected to a ventilator. An incision made on the chest exposes the pectoral muscles which will be cut to view the ribs. For ischemia/reperfusion studies, a 1 cm piece of PE tubing placed over the heart is used to tie the ligature to so that occlusion/reperfusion can be customized. For intramyocardial injections, a Hamilton syringe with sterile 30gauge beveled needle is used. When the myocardial manipulations are complete, the rib cage, the pectoral muscles, and the skin are closed sequentially. Line block analgesia is effected by 0.25% marcaine in sterile saline which is applied to muscle layer prior to closure of the skin. The mice are given a subcutaneous injection of saline and placed in a warming chamber until they are sternally recumbent. They are then returned to the vivarium and housed under standard conditions until the time of tissue collection. At the time of sacrifice, the mice are anesthetized, the heart is arrested in diastole with KCl or BDM, rinsed with saline, and immersed in fixative. Subsequently, routine procedures for processing, embedding, sectioning, and histological staining are performed. 
Nonsurgical intubation of a mouse and the microsurgical manipulations described make this a technically challenging model to learn and achieve reproducibility. These procedures, combined with the difficulty in performing consistent manipulations of the ligature for timed occlusion(s) and reperfusion or intramyocardial injections, can also affect the survival rate so optimization and consistency are critical.

Numerous genetic manipulations and/or intramyocardial injections of genes, proteins, cells, and/or biomaterials are superimposed upon the dimension of time in studies of acute ischemia/ reperfusion injury and chronic remodeling in mice. This video illustrates the microsurgical procedures for ischemia/reperfusion, permanent coronary artery ligation, and intramyocardial injection studies.

الشريان التاجي ربط Intramyocardial وحقن الفئران في نموذج من احتشاء

Mouse models are a valuable tool for studying acute injury and chronic remodeling of the myocardium in vivo.  With the advent of genetic modifications to ...

Permanent Ligation of the Left Anterior Descending Coronary Artery in Mice: A Model of Post-myocardial Infarction Remodelling and Heart Failure

Heart failure is a syndrome in which the heart fails to pump blood at a rate commensurate with 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 failure.
Ventricular remodelling refers to changes in structure, size, and shape of the left ventricle. 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. Since ventricular remodelling affects wall stress, it has a profound impact on cardiac function and on the development of heart failure. 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 reperfusion. In contrast, the infarct area at 24 hr 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.
Besides the model of permanent ligation of the left anterior descending coronary artery, the technique of invasive hemodynamic measurements in mice is presented in detail.

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.

ربط دائم في الشريان التاجي الأيسر الأمامي تنازلي في الفئران: نموذج ما بعد إعادة تشكيل عضلة القلب احتشاء وقصور القلب

Heart failure is a syndrome in which the heart fails to pump blood at a rate commensurate with cellular oxygen requirements at rest or during stress. It ...

Ultrasound Based Assessment of Coronary Artery Flow and Coronary Flow Reserve Using the Pressure Overload Model in Mice

Transthoracic Doppler echocardiography (TTDE) is a clinically useful, noninvasive tool for studying coronary artery flow velocity and coronary flow reserve (CFR) in humans. Reduced CFR is accompanied by marked intramyocardial and pericoronary fibrosis and is used as an indication of the severity of dysfunction. This study explores, step-by-step, the real-time changes measured in the coronary flow velocity, CFR and systolic to diastolic peak velocity (S/D) ratio in the setting of an aortic banding model in mice. By using a Doppler transthoracic imaging technique that yields reproducible and reliable data, the method assesses changes in flow in the septal coronary artery (SCA), for a period of over two weeks in mice, that previously either underwent aortic banding or thoracotomy. 
During imaging, hyperemia in all mice was induced by isoflurane, an anesthetic that increased coronary flow velocity when compared with resting flow. All images were acquired by a single imager. Two ratios, (1) CFR, the ratio between hyperemic and baseline flow velocities, and (2) systolic (S) to diastolic (D) flow were determined, using a proprietary software and by two independent observers. Importantly, the observed changes in coronary flow preceded LV dysfunction as evidenced by normal LV mass and fractional shortening (FS). 
The method was benchmarked against the current gold standard of coronary assessment, histopathology. The latter technique showed clear pathologic changes in the coronary artery in the form of peri-coronary fibrosis that correlated to the flow changes as assessed by echocardiography. 
The study underscores the value of using a non-invasive technique to monitor coronary circulation in mouse hearts. The method minimizes redundant use of research animals and demonstrates that advanced ultrasound-based indices, such as CFR and S/D ratios, can serve as viable diagnostic tools in a variety of investigational protocols including drug studies and the study of genetically modified strains.

Coronary flow reserve (CFR) is useful for assessment of myocardial oxygen demand and evaluation of cardiovascular risk. This study establishes a step-by-step transthoracic Doppler echocardiographic (TTDE) method for longitudinal monitoring of the changes in CFR, as measured from coronary artery in mice, under the experimental pressure overload of aortic banding.

تقييم الموجات فوق الصوتية وبناء من الشريان التاجي تدفق وتدفق التاجي الاحتياطي باستخدام نموذج الزائد الضغط في الفئران

Transthoracic Doppler echocardiography (TTDE) is a clinically useful, noninvasive tool for studying coronary artery flow velocity and coronary flow ...

Murine Left Anterior Descending (LAD) Coronary Artery Ligation: An Improved and Simplified Model for Myocardial Infarction

Ischemic heart disease (IHD), or acute coronary syndrome (ACS), is one of the leading causes of death in the United States. IHD is characterized by reduced blood supply to the heart, resulting in the loss of oxygen to and the ensuing necrosis of the heart muscle. The MI model has gained popularity for its use as a short-term ischemia-reperfusion model and a long-term permanent ligation model. Below, we describe a reliable method for the permanent ligation of the LAD. With mouse genetic engineering technology becoming more advanced, and with an increasing availability of quality murine surgical instruments, the mouse has become a popular model for MI surgeries. Our surgical model incorporates the use of an easily reversible anesthetic for the rapid recovery of the mouse; a minimally invasive endotracheal intubation without involving a tracheotomy; and a thoracentesis through the original thoracotomy site without creating an additional incision in the chest, as is done in some other methods, to effectively remove excess blood and air from the chest cavity. This method is comparatively less invasive than other methods, which dramatically reduces surgical and post-surgical complications and mortality and improves reproducibility.

Murine Left Anterior Descending LAD Coronary Artery Ligation: An Improved and Simplified Model for Myocardial Infarction

We provide a reliable method for left anterior descending artery (LAD) ligation in a mouse model. This method is comparatively less invasive than other methods, involving endotracheal intubation, a left-sided thoracotomy approach, and thoracentesis. This method can be used as a model for both acute and chronic myocardial infarction (MI).

الفئران اليسار الأمامي تنازلي (LAD) التاجي ربط الشريان: نموذج تحسين والمبسطة لاحتشاء عضلة القلب

Ischemic heart disease (IHD), or acute coronary syndrome (ACS), is one of the leading causes of death in the United States. IHD is characterized by ...

Direct Re-implantation of Left Coronary Artery into the Aorta in Adults with Anomalous Origin of Left Coronary Artery from the Pulmonary Artery (ALCAPA)

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital anomaly which is one of leading causes of myocardial ischemia and infarction in children. If left untreated, it results in a 90% mortality rate in the first year of life. In patients who survive to the adulthood, the coronary steal phenomenon and retrograde left-sided coronary flow provide a substrate for chronic subendocardial ischemia, which may lead to left ventricular dysfunction, ischemic mitral regurgitation, malignant ventricular arrhythmias, and sudden cardiac death. The average age of life-threatening presentation is 33 years and of sudden cardiac death 31 years. Therefore, surgical correction is highly recommended as soon as the diagnosis is made, regardless of age. In adult-type ALCAPA originating from the right-facing sinus of the pulmonary artery, direct re-implantation of the ALCAPA into the aorta is the more physiologically sound repair technique to re-establish the dual-coronary perfusion system and is recommended. This protocol describes the technique of direct re-implantation of adult-type ALCAPA into the aorta.

Direct Re-implantation of Left Coronary Artery into the Aorta in Adults with Anomalous Origin of Left Coronary Artery from the Pulmonary Artery ALCAPA

Surgical correction of ALCAPA is highly recommended, regardless of age or the degree of intercoronary collateralization. This protocol presents a technique for the direct re-implantation of adult-type ALCAPA into the aorta to re-establish the dual-coronary perfusion. Whenever feasible, direct re-implantation is preferred to other surgical correction techniques.

مباشر إعادة زرع الشريان التاجي الأيسر إلى الشريان الأبهر في البالغين الذين يعانون الشاذة منشأ الشريان التاجي الأيسر من الشريان الرئوي (ALCAPA)

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital anomaly which is one of leading causes of myocardial ...

Murine Myocardial Infarction Model using Permanent Ligation of Left Anterior Descending Coronary Artery

Myocardial infarction (MI) and acute coronary diseases are among the most prominent causes of death in population with western lifestyle. The murine models of MI with permanent ligation of left-anterior descending (LAD) coronary artery closely mimics MI in humans. Murine models benefit from the extensive genetic engineering available nowadays. Here we propose a reproducible murine surgical model of myocardial infarction by permanent LAD coronary ligation. Our technique comprises anesthesia with ketamine/xylazine that can be rapidly reversed by administration of an antagonist, intubation without tracheotomy for mechanical-assisted ventilation, ventilation with application of extrinsic positive end-expiratory pressure (PEEP) to avoid alveolar collapse, a thoracotomy method limiting to the minimum surgical lesions made to skeletal muscles, and lung inflation without thoracentesis. This method is sparsely invasive, reproducible and reduces post-surgery mortality and complications.

Herein we describe a surgical procedure showing how to achieve permanent ligation of the left-anterior descending coronary artery in mice. This model is of high relevance to investigate the pathophysiology of myocardial infarction and the concomitant biological processes.

نموذج احتشاء عضلة القلب Murine باستخدام الربط الدائم للشريان التاجي الأمامي الأيسر

Myocardial infarction (MI) and acute coronary diseases are among the most prominent causes of death in population with western lifestyle. The murine ...

Generation and Characterization of Right Ventricular Myocardial Infarction Induced by Permanent Ligation of the Right Coronary Artery in Mice

Right ventricular infarction (RVI) is a common presentation in clinical practice. Severe RVI can lead to fatal hemodynamic dysfunction and arrhythmia. In contrast to the extensively used mouse myocardial infarction (MI) model generated by left coronary artery ligation, the RVI mouse model is rarely employed due to the difficulty associated with model generation. Research on the mechanisms and treatment of RVI-induced RV remodeling and dysfunction requires animal models to mimic the pathophysiology of RVI in patients. This study introduces a feasible procedure for RVI model generation in C57BL/6J mice. Further, this model was characterized based on the following: infarct size evaluation at 24 h after MI, assessment of cardiac remodeling and function with echocardiography, RV hemodynamics assessment, and histology of the infarct zone at 4 weeks after RVI. In addition, a coronary vasculature cast was performed to observe the coronary arterial arrangement in RV. This mouse model of RVI would facilitate the research on mechanisms of right heart failure and seek new therapeutic targets of RV remodeling.

There are several differences between the right and left ventricles. However, the pathophysiology of right ventricular infarction (RVI) has not been clarified. In the present protocol, a reproducible method for RVI mouse model generation is introduced, which may provide a means to explain the mechanism of RVI.

توليد وتوصيف احتشاء عضلة القلب البطيني الأيمن الناجم عن الربط الدائم للشريان التاجي الأيمن في الفئران

Right ventricular infarction (RVI) is a common presentation in clinical practice. Severe RVI can lead to fatal hemodynamic dysfunction and arrhythmia. In ...

Left Coronary Artery Ligation: A Surgical Murine Model of Myocardial Infarction

Ischemic heart disease and subsequent myocardial infarction (MI) is one of the leading causes of mortality in the United States and around the world. In order to explore the pathophysiological changes after myocardial infarction and design future treatments, research models of MI are required. Permanent ligation of the left coronary artery (LCA) in mice is a popular model to investigate cardiac function and ventricular remodeling post MI. Here we describe a less invasive, reliable, and reproducible surgical murine MI model by permanent ligation of the LCA. Our surgical model comprises of an easily reversible general anesthesia, endotracheal intubation that does not require a tracheotomy, and a thoracotomy. Electrocardiography and troponin measurement should be performed to ensure MI. Echocardiography at day 28 after MI will discern heart function and heart failure parameters. The degree of cardiac fibrosis can be evaluated by Masson's trichrome staining and cardiac MRI. This MI model is useful for studying the pathophysiological and immunological alterations after MI.

Presented here is a surgical procedure for permanent ligation of the left coronary artery in mice. This model can be used to investigate the pathophysiology and associated inflammatory response after myocardial infarction.

ربط الشريان التاجي الأيسر: نموذج الفئران الجراحي لاحتشاء عضلة القلب

Ischemic heart disease and subsequent myocardial infarction (MI) is one of the leading causes of mortality in the United States and around the world. In ...

Left Anterior Descending Coronary Artery Ligation for Ischemia-Reperfusion Research: Model Improvement via Technical Modifications and Quality Control

Coronary heart disease is the leading cause of death globally. Complete cessation of blood flow in coronary arteries causes ST-segment elevation myocardial infarction (STEMI), resulting in cardiogenic shock and fatal arrhythmia, which are associated with high mortality. Primary coronary intervention (PCI) for recanalizing the coronary artery significantly improves the outcomes of STEMI, but advancements made in shortening the door-to-balloon time have failed to reduce in-hospital mortality, suggesting that additional therapeutic strategies are required. Left anterior descending coronary artery (LAD) ligation in rats is an animal model for acute myocardial IR research that is comparable to the clinical scenario in which rapid coronary recanalization through PCI is used for STEMI; however, PCI-induced STEMI is a technically challenging and complicated operation associated with high mortality and great variation in infarction size. We identified the ideal position for LAD ligation, created a gadget to control a snare loop, and supported a modified surgical maneuver, thereby reducing tissue damage, to establish a reliable and reproducible acute myocardial ischemia-reperfusion (IR) research protocol for rats. This is a non-survival surgery. We also propose a method for validating the quality of study results, which is a critical step for determining the accuracy of subsequent biochemical analyses.

Herein, we present a protocol focusing on the quality control of the left anterior descending coronary artery ligation by technically modifying the traditional procedure in rats for acute myocardial ischemia-reperfusion research.