arterial cannulation for ascending aortic banding in swine 

פסים עולים של אבי העורקים לחקר אי ספיקת לב הנגרמת על ידי עומס יתר בלחץ

Heart failure (HF) is a life-threatening disease that affects millions of people worldwide, causing major social and economic impacts1. One of its significant etiologies is aortic valve disease or aortic stenosis (AS). Aortic stenosis is more prevalent in advanced age and ranks as the second most common valvular lesion in the United States. AS-related mortality has also increased in Europe, particularly in countries without access to recent interventional procedures2. Given the complexity of HF and the scarcity of therapeutic innovations, there is a pressing need for reliable animal models that can replicate the human condition and facilitate the testing of new interventions3. While rodent models outnumber large animal models, the latter offers several advantages due to their size and physiological similarities, allowing the testing of drug doses and medical devices intended for human use.
The aim of this method is to establish a reproducible model of ascending aortic banding (AAB) applicable to most large animal species used in biomedical research. In this study, the procedure is demonstrated in swine using a minimally invasive approach, adhering to the 3Rs principles (replacement, reduction, and refinement4). This approach ensures the creation of an accurate pressure gradient, resulting in high reproducibility (potentially reducing the number of required animals). Additionally, the small surgical incision (2-3 cm) minimizes surgical insult, improving animal well-being compared to more aggressive approaches like sternotomy and larger thoracotomies5 (refinement). Furthermore, providing a video demonstration of the method, along with detailed descriptions in the literature, could potentially reduce the need for animals used solely for training purposes (replacement), further decreasing animal usage. This model can be adapted for different swine strains/breeds with distinct growth rates and induces sustained pressure overload, leading to significant hypertrophy after 1 or 2 months of follow-up.
Current methods employ fixed stenosis6, disregarding animal size variability, or calculate gradient using fluid-filled pressure readings7, which are less reliable than high-fidelity pressure sensors and are susceptible to signal damping8. Another approach uses a single pressure measurement distal to the stenosis5. However, calibrating the stenosis through simultaneous proximal and distal pressure signals using percutaneously delivered high-fidelity pressure sensors represents a substantial optimization of the protocol, resulting in improved group homogeneity. By visually demonstrating this method, other researchers should be able to replicate it without significant obstacles, increasing the availability of this model while promoting the application of the 3Rs principles.

מחבר זרקור: פיתוח מודל זעיר פולשני של בעלי חיים גדולים למחקר אמין וניתן לשחזור של הלב וכלי הדם 

מודל זעיר פולשני של היצרות אבי העורקים בחזירים

Most preclinical cardiovascular research is conducted on rodents and other small animal models. From a logistical, economic, reproducibility, and throughput perspective, it has obvious advantages. However, their phylogenetics, pathophysiological, and pharmacological responses are different from humans, and this may preclude the reliable translation to clinical use.Taking advantage of our highly specialized surgical and endovascular skillset, we have focused on developing surgical and they breed large animal models of common cardiac pathologies. This protocol is one good example of a simple, minimally invasive procedure that provides a good balance between reliability, reproducibility, and animal welfare. By monitoring the gradient in real time using high fidelity pressure sensors, we are able to accurately titrate the pressure gradient across the stenosis, resulting in a very homogeneous degree of severity between animals.Furthermore, the minimally invasive approach results in a much lower complication rate and better animal recovery. The development of large animal models, in this case swine, is promising for human-like pharmacological and device testing. This is particularly true for very sensitive areas where anatomophysiological similarities to humans are key, like anesthesia, cardiopulmonary bypass, ECMO, LVAS, percutaneous interest catheter therapies, and minimally invasive and robotic surgery.

Watch this Scientific Journal Video about Arterial Cannulation for Ascending Aortic Banding in Swine at JoVE.com

Arterial Cannulation for Ascending Aortic Banding in Swine   

קנולציה עורקית לפס אבי העורקים העולה בחזירים 

כדי להתחיל, לזהות את אתר לנקב עבור קנולציה עורקית בחזיר מורדם. באמצעות בדיקת כלי הדם, לזהות את עורק הירך המשותף ולאשר את המיקום של סמן אולטרסאונד עומק נכון. לפני הרכבת נדן המבוא, לשטוף את המבוא ואת מרחיב עם מלוחים heparinized.בהנחיית אולטרסאונד, הכנס מחט עורקי אקוגני לעורק הירך. ברגע שמגיעים ללומן העורקי ודם עורקי פועם יוצא ממרכז המחט, מקדמים חוט מנחה J-tip לתוך העורק. תוך שמירה על לחץ על אתר הניקוב, הסר את המחט, וקדם את מכלול המכנס והמרחיב לתוך העורק.לאחר מכן, להסיר את המרחיב ולשאוף את הדם מן היציאה הצדדית של המציג כדי לאשר את המיקום הנכון של המציג. שוטפים ברצף את המבוא במי מלח סטריליים. לבסוף, חבר קו לחץ עורקי ליציאה הצדדית של מבוא עורק הירך כדי לפקח על לחץ הדם.

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Research

JoVE Journal

Medicine

Arterial Cannulation for Ascending Aortic Banding in Swine 

108 Views.  University of Porto. כדי להתחיל, לזהות את אתר לנקב עבור קנולציה עורקית בחזיר מורדם. באמצעות בדיקת כלי הדם, לזהות את עורק הירך המשותף ולאשר את המיקום של סמן אולטרסאונד עומק נכון. לפני הרכבת נדן המבוא, לשטוף את המבוא ואת מרחיב עם מלוחים heparinized.בהנחיית אולטרסאונד, הכנס מחט עורקי אקוגני לעורק היר...

Video: Arterial Cannulation for Ascending Aortic Banding in Swine   

A Minimally Invasive Model of Aortic Stenosis in Swine

Large animal models of heart failure play an essential role in the development of new therapeutic interventions due to their size and physiological similarities to humans. Efforts have been dedicated to creating a model of pressure-overload induced heart failure, and ascending aortic banding while still supra-coronary and not a perfect mimic of aortic stenosis in humans, closely resembling the human condition.
The purpose of this study is to demonstrate a minimally invasive approach to induce left ventricular pressure overload by placing an aortic band, precisely calibrated with percutaneously introduced high-fidelity pressure sensors. This method represents a refinement of the surgical procedure (3Rs), resulting in homogenous trans-stenotic gradients and reduced intragroup variability. Additionally, it enables swift and uneventful animal recovery, leading to minimal mortality rates. Throughout the study, animals were followed for up to 2 months after surgery, employing transthoracic echocardiography and pressure-volume loop analysis. However, longer follow-up periods can be achieved if desired. This large animal model proves valuable for testing new drugs, particularly those targeting hypertrophy and the structural and functional alterations associated with left ventricular pressure overload.

This protocol describes a minimally invasive surgical procedure for ascending aortic banding in swine.

Large animal models of heart failure play an essential role in the development of new therapeutic interventions due to their size and physiological ...

To begin, identify the puncture site for arterial cannulation in an anesthetized pig. Using the vascular probe, identify the common femoral artery and confirm the position of the ultrasound marker and correct depth. Before assembling the introducer sheath, flush the introducer and dilator with heparinized saline.Under ultrasound guidance, insert an echogenic arterial needle into the femoral artery. Once the arterial lumen is reached and pulsating arterial blood comes out from the needle hub, advance a J-tip guidewire into the artery. While maintaining pressure on the puncture site, remove the needle, and advance the introducer and dilator assembly into the artery.Next, remove the dilator and aspirate the blood from the side port of the introducer to confirm the correct positioning of the introducer. Sequentially flush the introducer with sterile saline. Finally, connect an arterial pressure line to the side port of the femoral artery introducer to monitor blood pressure.

Ascending Aortic Banding and Left Ventricle/Aorta Catheterization in Swine for Pressure Measurements and Hemodynamic Monitoring 

After performing arterial cannulation in an anesthetized pig, using the cardiac ultrasound transducer, locate the position of the ascending aorta. Then mark the incision site and disinfect the chest of the animal. Using a scalpel, make a two to three centimeter skin incision at the level of the three-fourth intercostal space.Then dissect the underlying fascia and muscle layers until the intercostal space is reached. Stop the ventilation without positive and expiratory pressure. Incise the intercostal muscles to enter the thorax.Then increase the incision to allow the placement of the retractor blades. Retract the ribs and visualize the underlying structures. Using minimally invasive cardiac surgery forceps and scissors, open the pericardium.Then use with sterile gauze to retract the left atria and any lung tissue covering the view of the aorta. Carefully separate the aorta from the pulmonary artery until the transverse pericardial sinus is reached. To facilitate aortic catheterization, place a radiopaque marker in the banding area.Position the ePTFE graft or the nylon band around the ascending aorta. Connect a dual hemostasis valve adapter to a six French MP1 guide catheter, and flush it with heparinized saline. Preload the guide catheter with a 260-centimeter 0.035-inch J-tip guidewire and introduce this assembly through the femoral arterial sheath.Under fluoroscopic guidance, advance the guide wire and guide the catheter into the ascending aorta. When the aortic valve is identified, carefully cross it with a guidewire and introduce the guide catheter into the left ventricle. Check pressure traces to confirm left ventricle positioning.Next, remove the guidewire while leaving the guide catheter in the left ventricle. After aspirating the blood, flush the catheter with sterile saline and ensure no air bubbles are present in the catheter. After advancing two high-fidelity pressure sensors through the dual hemostasis valve adapter, pull the guide catheter back into the ascending aorta distally to the radiopaque marker placed on the banding site.While leaving one of the high-fidelity pressure sensors in the left ventricle, confirm the catheter position using pressure traces. After left ventricle catheterization, close the nylon band one click at a time while closely monitoring pressures. Place sterile plastic tubing on the nylon band end to avoid accidental damage to the surrounding structures.for ePTFE ends, constrict the band using 45-degree forceps. Monitor the pressure to estimate the relative location of the constriction. Finally, place a titanium hemoclip on the forceps position.The use of high fidelity pressure sensors enables obtaining high quality pressure signals, allowing real time and accurate calibration of the stenosis. Transthoracic echocardiography confirm significant aortic stenosis immediately after surgery and during follow-up. Banding surgery resulted in significant aortic stenosis and left ventricular concentric hypertrophy.Post-mortem macroscopic analysis of the heart revealed larger hearts and a thicker left ventricular wall.