The authors have nothing to disclose.

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The authors would like to thank the INRA institute, which housed the piglets, and Cardio Innovating systems for the funding.

لأول مرة، وقد تبين أن التغيرات في تدفق نابض الرئوي علاقة سببية تطوير الهيئة العامة للإسكان الثانوي التعرض المزمن ميتة. هذا النهج متعدية يوفر أدلة على أن يحفز زيادة مصطنعة في الرئوي تدفق نابض باستخدام القسطرة التي صممت خصيصا يحسن ارتفاع ضغط الدم الرئوي، وربما عن طريق...

ارتفاع ضغط الدم الشرياني الرئوي هو مرض مهدد للحياة التي تؤثر على الأوعية الدموية الرئوية. وهناك اتفاق في الحقل الذي اختلال التوازن بين الزيادة في vasoconstrictors (endothelin، السيروتونين) وانخفاض في موسعات (NO، بروستاسيكلين) يساهم في تطوير الهيئة العامة للإسكان. مع مرور الوقت، وهذا النمط الظاهري الموالية للالتضييقية يتطور إلى النمط الظاهري الموالية للالتكاثري ومكافحة أفكارك معقدة، والمساهمة في تطوير الآفات الوعائية 1. التعرض لفترات طويلة للvasoconstrictors يؤدي إلى زيادة كبيرة ومطردة في [كا 2+] أنا في الشريان الرئوي خلايا العضلات الملساء، مما يسمح تفعيل عدة عوامل النسخ التنظيم الكالسيوم، مثل NFAT 2-4، وتعزيز انتشار PASMC والمقاومة ل موت الخلايا المبرمج النمط الظاهري 5. هذا النمط الظاهري يؤدي إلى آفات الأوعية الدموية الرئوية، مما يساهم في زيادة في كل من ضغط السلطة الفلسطينية والدقة الرئويةistance، الأمر الذي يؤدي في نهاية المطاف إلى قاتل فشل القلب الأيمن (6). حاليا، لا يوجد علاج المتاحة التي يعكس الهيئة العامة للإسكان على الرغم من أن هناك العديد من شأنها تحسين نوعية حياة المريض 7. من بين هذه العلاجات، فقد ثبت فعالية استنشاق NO العلاج ولكن بسبب قصيرة العمر النصفي لأنه من الصعب استخدامها في الممارسة السريرية. لهذا السبب، قد يفضل العلاجات أكثر استقرارا ودواما، مثل النظير بروستاسيكلين، أو حاصرات مستقبلات endothelin 7. لتطوير علاجات أفضل، لا بد من تحسين وتوسيع معرفة الفيزيولوجيا المرضية من الهيئة العامة للإسكان. Pulsatility هو التحفيز معروفة تفعيل القص الإجهاد الناجم عن توسع الأوعية، وحماية الشرايين القاصي غير مرنة من الإصابات تدفق الضغط العالي 8،9. في نموذج من الهيئة العامة للإسكان الثانوي إلى أبهري رئوي السحب الجراحية، نور وآخرون أظهرت داخل الرئة القص شارعبوساطة وفاق سطيف وظيفة بطانة الأوعية الدموية تعزيز 10. وقد أثبتت العديد من الدراسات أن NO، بروستاسيكلين وET-1 التعبير وينظم عن كثب التغيرات في تدفق نابض. في الواقع، زيادة معتدلة في تدفق نابض يزيد النشاط أنوش ومستويات بروستاسيكلين، وكلاهما يتم تخفيض في الهيئة العامة للإسكان. تعديل تدفق نابض وربما تورط في المسببات من الهيئة العامة للإسكان وزيادة مصطنعة هو وسيلة جذابة ومبتكرة لزيادة NO والإنتاج بروستاسيكلين في الدورة الدموية الرئوية. وتهدف هذه الدراسة إلى تقييم الآثار المترتبة على نابض 10 دقيقة تدفق باستخدام القسطرة نابض وضعت حديثا على قياسات الدورة الدموية في ارتفاع ضغط الدم الرئوي (PH) نموذج في الخنازير ومنهم من تم يسببها نقص الأكسجة. فقد تم الافتراض أن زيادة الشريان الرئوي pulsatility يدفع ارتخاء وعائي الشرايين الرئوية، مما يقلل ضغط الشريان الرئوي. الصحيح القط القلبheterization (RHC) هو التدخل السريري حاسم لتشخيص ومتابعة مرضى الهيئة العامة للإسكان. في الواقع، هذا هو السبيل الأكثر موثوقية لتشخيص الهيئة العامة للإسكان، ويسمح الأطباء لتقييم تفاعل الأوعية الدموية 11،12 فضلا عن تطور المرض. في الواقع كل مريض الهيئة العامة للإسكان يخضع RHC عدة مرات. وتهدف هذه الدراسة في الحيوانات الكبيرة لإثبات فعالية وسلامة القسطرة نابض في تقييم وعلاج PAH أثناء إجراء RHC منتظم. لأن القسطرة نابض متاحة بالفعل، ويتم تنفيذها RHC بشكل روتيني في المرضى الذين يعانون الهيئة العامة للإسكان، توفر هذه الدراسة جميع المعلومات المطلوبة لتكون قادرة على إجراء التجارب السريرية بسرعة.

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	<tbody>
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			<td height="17" style="height:17px;width:311px;">Drugs for anesthesia</td>
			<td style="width:336px;"></td>
			<td style="width:141px;"></td>
			<td style="width:224px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">sodium thiopental, THIOPENTAL SODIUM</td>
			<td>Abbott, France</td>
			<td>0000071-73-8</td>
			<td>powder 
			3 place Gustave Eiffe 94518 RUNGIS CEDEX.</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">&#160;isoflurane, FORANE</td>
			<td>Abbott, France</td>
			<td style="width:141px;">05260-05</td>
			<td>glass bottle 250 ml 
			3 place Gustave Eiffe 94518 RUNGIS CEDEX.</td>
		</tr>
		<tr height="17">
			<td height="17" style="height:17px;">midazolam, Hypnovel</td>
			<td>Accord Healthcare&#160;</td>
			<td>Vidal</td>
			<td>injectable ampoules 1mg/ml 
			45 Rue du Faubourg de Roubaix 59000 Lille France</td>
		</tr>
		<tr height="17">
			<td height="17" style="height:17px;">pramocaine,TRONOTHANE 1 %&#160;</td>
			<td>Laboratoires LISAPHARM</td>
			<td>Vidal</td>
			<td>Gel appl locale T/30g 
			3, rue Scheffer. 75016 Paris.</td>
		</tr>
		<tr height="17">
			<td height="17" style="height:17px;">morphine chlohydrate Lavoisier</td>
			<td>CMD Lavoisier Laboratoires CHAIX et DU MARAIS</td>
			<td>Vidal</td>
			<td>injectable ampoules&#160; 
			7, rue Labie -75017 Paris - France</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:311px;">Acrylates Copolymer-Carbopol&#174; Aqua SF-1 Polymer</td>
			<td>Lubrizol</td>
			<td></td>
			<td>gel appl local 
			Elys&#233;es La D&#233;fense 19 le Parvis 92073 Paris la d&#233;fense</td>
		</tr>
		<tr height="17">
			<td height="17" style="height:17px;">Material&#160;</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Ventilateur Harvard 683</td>
			<td>Harvard apparatus</td>
			<td>Harvard apparatus</td>
			<td>DRIM 75 rue des Anglais - 78700 Conflans Ste Honorine &#160;&#160;</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Echographe Voluson E8 with a 3,5 MHz probe</td>
			<td>General Electric</td>
			<td>GEHealthcare</td>
			<td>DRIM 75 rue des Anglais - 78700 Conflans Ste Honorine &#160;&#160;</td>
		</tr>
		<tr height="17">
			<td height="17" style="height:17px;">Pulsatil Catheter</td>
			<td>Cardio inovating system</td>
			<td></td>
			<td>Cardio innovative systems, 33 rue Vivienne, Paris, France 75002</td>
		</tr>
		<tr height="17">
			<td height="17" style="height:17px;">NO breath Analyseur</td>
			<td>Respur</td>
			<td>Respur</td>
			<td>26 rue Felix Rouget 95490 Vaureal France</td>
		</tr>
	</tbody>
</table>

increasing pulmonary artery pulsatile flow improves hypoxic pulmonary hypertension in piglets

ارتفاع ضغط الدم الشرياني الرئوي (الهيئة العامة للإسكان) هو مرض يصيب الشرايين الرئوية البعيدة (PA). هذه الشرايين هي مشوهة، مما أدى إلى فشل البطين الأيمن. العلاجات الحالية محدودة. من الناحية الفسيولوجية، وتدفق الدم نابض يضر الأوعية الدموية. ردا على الإجهاد نابض مستمرة، سفن تطلق أكسيد النيتريك (NO) للحث على توسع الأوعية للدفاع عن النفس. وبناء على هذه الملاحظة، وضعت هذه الدراسة على بروتوكول لتقييم ما إذا كان الاصطناعي الرئوي تدفق الدم نابض يمكن أن يفضي إلى انخفاض تعتمد على NO في ضغط الشريان الرئوي. تعرضت مجموعة من الخنازير إلى نقص الأكسجة المزمن لمدة 3 أسابيع ومقارنة مع مجموعة السيطرة على الخنازير. مرة واحدة في الأسبوع، خضعت الخنازير تخطيط صدى القلب لتقييم شدة الهيئة العامة للإسكان. في نهاية التعرض نقص الأكسجين، وتعرضوا الخنازير في بروتوكول نابض باستخدام القسطرة نابض. بعد تخدير وإعداد لعملية جراحية، وكان حبل الوريد من خنزير صغير معزول وCAوقدم theter من خلال الأذين الأيمن والبطين الأيمن والشريان الرئوي، بالتصوير بالأشعة تحت السيطرة. وقد تم قياس ضغط الشريان الرئوي (PAP) قبل (T0)، مباشرة بعد (T1) و 30 دقيقة بعد (T2) بروتوكول نابض. وقد تبين أن هذا البروتوكول نابض هو وسيلة آمنة وفعالة على إحداث خفض كبير في متوسط ​​PAP عبر آلية NO-تعتمد. فتح هذه البيانات آفاقا جديدة لإدارة السريرية للالهيئة العامة للإسكان.

زيادة الشريان الرئوي نابض تدفق يحسن المستحثة المزمن نقص الأوكسجين ارتفاع ضغط الدم الرئوي في الخنازير قبل تعريض الحيوانات إلى زيادة في تدفق نابض، تم استخدام الموجات فوق الصوتية غير جراحية للتأكد من أن الخنازير قد وضعت ارتفاع ضغط...

Watch this Scientific Journal Video about Increasing Pulmonary Artery Pulsatile Flow Improves Hypoxic Pulmonary Hypertension in Piglets at JoVE.com

زيادة التدفق النابض للشريان الرئوي يحسن ارتفاع ضغط الدم الرئوي الناتج عن نقص التأكسج في الخنازير | طب | فيديو

Increasing Pulmonary Artery Pulsatile Flow Improves Hypoxic Pulmonary Hypertension in Piglets

Pulmonary hypertension is associated with a significant reduction in pulmonary artery pulsatility, contractility and elasticity, contributing to an increase in pulmonary artery pressure and pulmonary resistance. Using a hypoxic piglet model, this study demonstrated that improving pulmonary artery plasticity using a newly developed pulsatile catheter improves hypoxic pulmonary hypertension.

زيادة الشريان الرئوي نابض تدفق يحسن نقص الأوكسجين ارتفاع ضغط الدم الرئوي في الخنازير

Pulmonary arterial hypertension (PAH) is a disease affecting distal pulmonary arteries (PA). These arteries are deformed, leading to right ventricular ...

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14.0K Views.  Laval University. Pulmonary hypertension is associated with a significant reduction in pulmonary artery pulsatility, contractility and elasticity, contributing to an increase in pulmonary artery pressure and pulmonary resistance. Using a hypoxic piglet model, this study demonstrated that improving pulmonary artery plasticity using a newly developed pulsatile catheter improves hypoxic pulmonary hypertension.

Video: Increasing Pulmonary Artery Pulsatile Flow Improves Hypoxic Pulmonary Hypertension in Piglets

Human Internal Mammary Artery (IMA) Transplantation and Stenting: A Human Model to Study the Development of In-Stent Restenosis

Preclinical in vivo research models to investigate pathobiological and pathophysiological processes in the development of intimal hyperplasia after vessel stenting are crucial for translational approaches1,2.
The commonly used animal models include mice, rats, rabbits, and pigs3-5. However, the translation of these models into clinical settings remains difficult, since those biological processes are already studied in animal vessels but never performed before in human research models6,7. In this video we demonstrate a new humanized model to overcome this translational gap. The shown procedure is reproducible, easy, and fast to perform and is suitable to study the development of intimal hyperplasia and the applicability of diverse stents.
This video shows how to perform the stent technique in human vessels followed by transplantation into immunodeficient rats, and identifies the origin of proliferating cells as human.

Human Internal Mammary Artery IMA Transplantation and Stenting: A Human Model to Study the Development of In-Stent Restenosis

This video shows a model to study the development of intimal hyperplasia after stent deployment using a human vessel (IMA) in an immunodeficient rat model.

الداخلية الثديية البشرية الشريان (IMA) وزرع الدعامات: نموذج الإنسان لدراسة تطوير داخل الدعامة عودة التضيق

Preclinical in vivo research models to investigate pathobiological and pathophysiological processes in the development of intimal hyperplasia after vessel ...

Videomorphometric Analysis of Hypoxic Pulmonary Vasoconstriction of Intra-pulmonary Arteries Using Murine Precision Cut Lung Slices

Acute alveolar hypoxia causes pulmonary vasoconstriction (HPV) - also known as von Euler-Liljestrand mechanism - which serves to match lung perfusion to ventilation. Up to now, the underlying mechanisms are not fully understood. The major vascular segment contributing to HPV is the intra-acinar artery. This vessel section is responsible for the blood supply of an individual acinus, which is defined as the portion of lung distal to a terminal bronchiole. Intra-acinar arteries are mostly located in that part of the lung that cannot be selectively reached by a number of commonly used techniques such as measurement of the pulmonary artery pressure in isolated perfused lungs or force recordings from dissected proximal pulmonary artery segments1,2. The analysis of subpleural vessels by real-time confocal laser scanning luminescence microscopy is limited to vessels with up to 50 &#181;m in diameter3.
We provide a technique to study HPV of murine intra-pulmonary arteries in the range of 20-100 &#181;m inner diameters. It is based on the videomorphometric analysis of cross-sectioned arteries in precision cut lung slices (PCLS). This method allows the quantitative measurement of vasoreactivity of small intra-acinar arteries with inner diameter between 20-40 &#181;m which are located at gussets of alveolar septa next to alveolar ducts and of larger pre-acinar arteries with inner diameters between 40-100 &#181;m which run adjacent to bronchi and bronchioles. In contrast to real-time imaging of subpleural vessels in anesthetized and ventilated mice, videomorphometric analysis of PCLS occurs under conditions free of shear stress. In our experimental model both arterial segments exhibit a monophasic HPV when exposed to medium gassed with 1% O2 and the response fades after 30-40 min at hypoxia.

Hypoxic pulmonary vasoconstriction (HPV) is an important physiological phenomenon by which at alveolar hypoxia lung perfusion is matched to ventilation. The major vascular segment contributing to HPV is the intra-acinar artery. Here, we describe our protocol for the analysis of HPV of murine pulmonary vessels with diameters of 20-100 &mu;m.

تحليل مجسم الفيديو لنقص الأكسجين الرئوي من الشرايين داخل الرئة باستخدام مورين الدقة قطع شرائح الرئة

Acute alveolar hypoxia causes pulmonary vasoconstriction (HPV) - also known as von Euler-Liljestrand mechanism - which serves to match lung perfusion to ...

Automated Measurement of Microcirculatory Blood Flow Velocity in Pulmonary Metastases of Rats

Because the lung is a major target organ of metastatic disease, animal models to study the physiology of pulmonary metastases are of great importance. However, very few methods exist to date to investigate lung metastases in a dynamic fashion at the microcirculatory level, due to the difficulty to access the lung with a microscope. Here, an intravital microscopy method is presented to functionally image and quantify the microcirculation of superficial pulmonary metastases in rats, using a closed-chest pulmonary window and automated analysis of blood flow velocity and direction. The utility of this method is demonstrated to measure increases in blood flow velocity in response to pharmacological intervention, and to image the well-known tortuous vasculature of solid tumors. This is the first demonstration of intravital microscopy on pulmonary metastases in a closed-chest model. Because of its minimized invasiveness, as well as due to its relative ease and practicality, this technology has the potential to experience widespread use in laboratories that specialize on pulmonary tumor research.

A method is presented to measure microcirculatory blood flow velocity in pulmonary cancer metastases of the pleural surface in rats in an automated fashion, using closed-chest pulmonary intravital microscopy. This model has potential to be used as a widespread tool to perform physiologic research on pulmonary metastases in rodents.

القياس الآلي من الأوعية الدقيقة سرعة تدفق الدم في الرئة الانبثاث من الجرذان

Because the lung is a major target organ of metastatic disease, animal models to study the physiology of pulmonary metastases are of great importance. ...

Chronic Thromboembolic Pulmonary Hypertension and Assessment of Right Ventricular Function in the Piglet

An original piglet model of Chronic Thromboembolic Pulmonary Hypertension (CTEPH) associated with chronic Right Ventricular (RV) dysfunction is described. Pulmonary Hypertension (PH) was induced in 3-week-old piglets by a progressive obstruction of the pulmonary vascular bed. A ligation of the left Pulmonary Artery (PA) was performed first through a mini-thoracotomy. Second, weekly embolizations of the right lower pulmonary lobe were done under fluoroscopic guidance with n-butyl-2-cyanoacrylate during 5 weeks. Mean Pulmonary Arterial Pressure (mPAP) measured by ritght heart catheterism, increased progressively, as well as Right Atrial pressure and Pulmonary Vascular Resistances (PVR) after 5 weeks compared to sham animals. Right Ventricular (RV) structural and functional remodeling were assessed by transthoracic echocardiography (RV diameters, RV wall thickness, RV systolic function). RV elastance and RV-pulmonary coupling were assessed by Pressure-Volume Loops (PVL) analysis with conductance method. Histologic study of the lung and the right ventricle were also performed. Molecular analyses on RV fresh tissues could be performed through repeated transcutaneous endomyocardial biopsies. Pulmonary microvascular disease in obstructed and unobstructed territories was studied from lung biopsies using molecular analyses and pathology. Furthermore, the reliability and the reproducibility was associated with a range of PH severity in animals. Most aspects of the human CTEPH disease were reproduced in this model, which allows new perspectives for the understanding of the underlying mechanisms (mitochondria, inflammation) and new therapeutic approaches (targeted, cellular or gene therapies) of the overloaded right ventricle but also pulmonary microvascular disease.

Chronic Thromboembolic Pulmonary Hypertension (CTEPH) and Right Ventricular (RV) dysfunction were induced in piglets by progressive obstruction of the pulmonary arteries. Consequences were remarkably similar to those observed in CTEPH patients. This animal model would be a very useful tool for pathophysiology and therapeutic experiments on CTEPH and RV failure.

الانصمام الخثاري المزمن ارتفاع ضغط الدم الرئوي وتقييم الحق البطيني وظيفة في الخنزير الصغير

An original piglet model of Chronic Thromboembolic Pulmonary Hypertension (CTEPH) associated with chronic Right Ventricular (RV) dysfunction is described. ...

Hemodynamic Characterization of Rodent Models of Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a rare disease of the pulmonary vasculature characterized by endothelial cell apoptosis, smooth muscle proliferation and obliteration of pulmonary arterioles. This in turn results in right ventricular (RV) failure, with significant morbidity and mortality. Rodent models of PAH, in the mouse and the rat, are important for understanding the pathophysiology underlying this rare disease. Notably, different models of PAH may be associated with different degrees of pulmonary hypertension, RV hypertrophy and RV failure. Therefore, a complete hemodynamic characterization of mice and rats with PAH is critical in determining the effects of drugs or genetic modifications on the disease. 
Here we demonstrate standard procedures for assessment of right ventricular function and hemodynamics in both rat and mouse PAH models. Echocardiography is useful in determining RV function in rats, although obtaining standard views of the right ventricle is challenging in the awake mouse. Access for right heart catheterization is obtained by the internal jugular vein in closed-chest mice and rats. Pressures can be measured using polyethylene tubing with a fluid pressure transducer or a miniature micromanometer pressure catheter. Pressure-volume loop analysis can be performed in the open chest. After obtaining hemodynamics, the rodent is euthanized. The heart can be dissected to separate the RV free wall from the left ventricle (LV) and septum, allowing an assessment of RV hypertrophy using the Fulton index (RV/(LV+S)). Then samples can be harvested from the heart, lungs and other tissues as needed.

Pulmonary arterial hypertension (PAH) is a disease of pulmonary arterioles that leads to their obliteration and the development of right ventricular failure. Rodent models of PAH are critical in understanding the pathophysiology of PAH. Here we demonstrate hemodynamic characterization, with right heart catheterization and echocardiography, in the mouse and rat.

الدورة الدموية توصيف نماذج القوارض من الرئوي الشرياني ارتفاع ضغط الدم

Pulmonary arterial hypertension (PAH) is a rare disease of the pulmonary vasculature characterized by endothelial cell apoptosis, smooth muscle ...

Shunt Surgery, Right Heart Catheterization, and Vascular Morphometry in a Rat Model for Flow-induced Pulmonary Arterial Hypertension

In this protocol, PAH is induced by combining a 60 mg/kg monocrotalin (MCT) injection with increased pulmonary blood flow through an aorto-caval shunt (MCT+Flow). The shunt is created by inserting an 18-G needle from the abdominal aorta into the adjacent caval vein. Increased pulmonary flow has been demonstrated as an essential trigger for a severe form of PAH with distinct phases of disease progression, characterized by early medial hypertrophy followed by neointimal lesions and the progressive occlusion of the small pulmonary vessels. To measure the right heart and pulmonary hemodynamics in this model, right heart catheterization is performed by inserting a rigid cannula containing a flexible ball-tip catheter via the right jugular vein into the right ventricle. The catheter is then advanced into the main and the more distal pulmonary arteries. The histopathology of the pulmonary vasculature is assessed qualitatively, by scoring the pre- and intra-acinar vessels on the degree of muscularization and the presence of a neointima, and quantitatively, by measuring the wall thickness, the wall-lumen ratios, and the occlusion score.

This protocol describes a surgical procedure to create a model for flow-induced pulmonary arterial hypertension (PAH) in rats and the procedures to analyze the principle hemodynamic and histological end-points in this model.

جراحة التحويلة، الحق القلب قسطرة، والأوعية الدموية القياس الشكلي في الفأر نموذج لالناجم عن تدفق-الرئوي الشرياني ارتفاع ضغط الدم

In this protocol, PAH is induced by combining a 60 mg/kg monocrotalin (MCT) injection with increased pulmonary blood flow through an aorto-caval shunt ...

Murine Echocardiography of Left Atrium, Aorta, and Pulmonary Artery

The present methodology teaches the investigator how to measure and use the LAV as a surrogate of chronic elevations in Left Ventricular diastolic pressure through echocardiography, as well as to obtain measurements of the Aorta and PA diameter in mice.
Mice older than 10 d of age can be analyzed using the present technique. The technique is composed of 3 main steps: set-up, image acquisition, and image analysis. The set-up step consists of getting the mouse anesthetized with 1% isoflurane, shaving it, and taping it in a supine position to a heated EKG board where the image acquisition will take place. The image acquisition step consists of learning to identify the cardiac structures and obtaining all the required images with its correspondent probe and axis in order to be able to calculate volumes and diameters. The image analysis step consists of measuring the previously acquired images with the aid of computer software.
Advantages of the proposed technique include a fast (15 min) procedure that would allow the researcher to evaluate interventions in a non-invasive, non-terminal approach and therefore follow the same mouse over time; each mouse can be used as its own control. This fact plus having the same operator perform all the acquisition and analysis for the entire experiment minimizes the limitation of operator-dependency. The present methodology is useful for mouse researchers in cardiovascular and pulmonary medicine.

The following protocol describes the methodology for the acquisition and analysis of echocardiographic images used to obtain the Left Atrial Volume (LAV), Aorta (Ao) diameter, and Pulmonary Artery (PA) diameter in mice. This technique is a non-invasive, non-terminal procedure that allows assessment of the cardiopulmonary function.

فأري ضربات القلب من الأذين الأيسر، الأورطي، والشريان الرئوي

The present methodology teaches the investigator how to measure and use the LAV as a surrogate of chronic elevations in Left Ventricular diastolic ...

Left Atrial Stenosis Induced Pulmonary Venous Arterialization and Group 2 Pulmonary Hypertension in Rat

The mechanism of mitral stenosis-induced pulmonary venous arterialization and group 2 pulmonary hypertension (PH) is unclear. There is no rodent model of group 2 PH, due to mitral stenosis (MS), to facilitate the investigation of disease mechanisms and potential therapeutic strategies. We present a novel rat model of pulmonary venous congestion-induced pulmonary venous arterialization and group 2 PH caused by left atrial stenosis (LAS). LAS is achieved by constricting the left atrium using a half-closed titanium clip. After the LAS surgery, a rat model with a transmitral inflow velocity greater than or equal to 2.0 m/s on echocardiography gradually develops pulmonary venous arterialization and group 2 PH over an 8- to 10-week period. In this protocol, we provide the step-by-step procedure of how to perform the LAS surgery. The presented LAS rat model mimics MS in humans and is useful for studying the underlying molecular mechanism of pulmonary venous arterialization and for the preclinical evaluation of therapies for group 2 PH.

Left atrial stenosis (LAS) is a novel surgical technique used for studying group 2 pulmonary hypertension (PH) and mechanisms underlying pulmonary venous arterialization. Here, we present a protocol to constrict the left atrium using a titanium clip to cause pulmonary venous arterialization and moderate PH in a rat.

تضيق أذينية الأيسر الناجم عن أرتيرياليزيشن الوريدي الرئوي وارتفاع ضغط الدم الرئوي المجموعة 2 في الفئران

The mechanism of mitral stenosis-induced pulmonary venous arterialization and group 2 pulmonary hypertension (PH) is unclear. There is no rodent model of ...

The Left Pneumonectomy Combined with Monocrotaline or Sugen as a Model of Pulmonary Hypertension in Rats

In this protocol, we detail the correct procedural steps and necessary precautions to successfully perform a left pneumonectomy and induce PAH in rats with the additional administration of monocrotaline (MCT) or SU5416 (Sugen). We also compare these two models to other PAH models commonly used in research. In the last few years, the focus of animal PAH models has moved towards studying the mechanism of angioproliferation of plexiform lesions, in which the role of increased pulmonary blood flow is considered as an important trigger in the development of severe pulmonary vascular remodeling. One of the most promising rodent models of increased pulmonary flow is the unilateral left pneumonectomy combined with a "second hit" of MCT or Sugen. The removal of the left lung leads to increased and turbulent pulmonary blood flow and vascular remodeling. Currently, there is no detailed procedure of the pneumonectomy surgery in rats. This article details a step-by-step protocol of the pneumonectomy surgical procedure and post-operative care in male Sprague-Dawley rats. Briefly, the animal is anesthetized and the chest is opened. Once the left pulmonary artery, pulmonary vein, and bronchus are visualized, they are ligated and the left lung is removed. The chest then closed and the animal recovered. Blood is forced to circulate only on the right lung. This increased vascular pressure leads to a progressive remodeling and occlusion of small pulmonary arteries. The second hit of MCT or Sugen is used one week post-surgery to induce endothelial dysfunction. The combination of increased blood flow in the lung and endothelial dysfunction produces severe PAH. The primary limitation of this procedure is that it requires general surgical skills.

The rodent left pneumonectomy is a valuable technique in pulmonary hypertension research. Here, we present a protocol to describe the rat pneumonectomy procedure and postoperative care to ensure minimal morbidity and mortality.

بنيومونيكتومي اليسرى جنبا إلى جنب مع مونوكروتاليني أو سكر كنموذج لارتفاع ضغط الدم الرئوي في الفئران

In this protocol, we detail the correct procedural steps and necessary precautions to successfully perform a left pneumonectomy and induce PAH in rats ...

Induction and Characterization of Pulmonary Hypertension in Mice using the Hypoxia/SU5416 Model

Pulmonary Hypertension (PH) is a pathophysiological condition, defined by a mean pulmonary arterial pressure exceeding 25 mm Hg at rest, as assessed by right heart&#160;catheterization. A broad spectrum of diseases can lead to PH, differing in their etiology, histopathology, clinical presentation, prognosis, and response to&#160;treatment. Despite significant progress in the last years, PH remains an uncured disease. Understanding the underlying mechanisms can pave the way for the development of new therapies. Animal models are important research tools to achieve this goal. Currently, there are several models available for recapitulating PH. This protocol describes a two-hit mouse PH model. The stimuli for PH development are hypoxia and the injection of SU5416, a vascular endothelial growth factor (VEGF) receptor antagonist. Three weeks after initiation of Hypoxia/SU5416, animals develop pulmonary vascular remodeling imitating the histopathological changes observed in human PH (predominantly Group 1). Vascular remodeling in the pulmonary circulation results in the remodeling of the right&#160;ventricle (RV). The procedures for measuring RV pressures (using the open chest method), the morphometrical analyses of the RV (by dissecting and weighing both cardiac ventricles) and the histological assessments of the remodeling (both pulmonary by assessing vascular remodeling and cardiac by assessing RV cardiomyocyte hypertrophy and fibrosis) are described in detail. The advantages of this protocol are the possibility of the application both in wild type and in genetically modified mice, the relatively easy and low-cost implementation, and the quick development of the disease of interest (3 weeks). Limitations of this method are that mice do not develop a severe phenotype and PH is reversible upon return to normoxia. Prevention, as well as therapy studies, can easily be implemented in this model, without the necessity of advanced skills (as opposed to surgical rodent models).

This protocol describes the induction of pulmonary hypertension (PH) in mice based on the exposure to hypoxia and the injection of a VEGF receptor antagonist. The animals develop PH and right ventricular (RV) hypertrophy 3 weeks after the initiation of the protocol. The functional and morphometrical characterization of the model is also presented.

التعريفي وتوصيف ارتفاع ضغط الدم الرئوي في الفئران باستخدام نموذج نقص الأكسجة/SU5416

Pulmonary Hypertension (PH) is a pathophysiological condition, defined by a mean pulmonary arterial pressure exceeding 25 mm Hg at rest, as assessed by ...