Name: Rat Model of Right-Sided Cardiac Remodeling and Arrhythmia Using Pulmonary Artery Banding (Video) | JoVE Journal
Uploaded: 2024-08-30T13:20:00.000+00:00
Duration: 10 min 39 s
Description: Learn pulmonary artery banding in rats to model right heart failure and study inflammation-driven cardiac arrhythmias. This method enables detailed echocardiographic assessment of atrial fibrillation mechanisms.

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5 minutes

The authors are thankful to Colombe Roy, YanFen Shi, Sandra Querry, and Josiane Deslandes for the technical performance of transthoracic echocardiography and to Nathalie L&#39;Heureux for preliminary technical assistance during the standardization of the PAB method. We are grateful to the members of the animal care facility of the Montreal Heart Institute.

Optimizing Pulmonary Artery Banding for Consistent Right Heart Failure Induction

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<li>Prihadi, E. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Morphologic+types+of+tricuspid+regurgitation.+Characteristics+and+prognostic+implications%5BTitle%5D)+AND+%22JACC%3A+Cardiovasc+Imaging%22%5BJournal%5D)">Morphologic types of tricuspid regurgitation. Characteristics and prognostic implications.</a> JACC: Cardiovasc Imaging. 12 (3), 491-499 (2019).</li>
<li>Samson, N., Paulin, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Epigenetics%2C+inflammation+and+metabolism+in+right+heart+failure+associated+with+pulmonary+hypertension%5BTitle%5D)+AND+%22Pulm+Circ%22%5BJournal%5D)">Epigenetics, inflammation and metabolism in right heart failure associated with pulmonary hypertension.</a> Pulm Circ. 7 (3), 572-587 (2017).</li>
<li>Liu, Z., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Low-voltage+zones+as+the+atrial+fibrillation+substrates%3A+Relationship+With+initiation%2C+perpetuation%2C+and+termination%5BTitle%5D)+AND+%22Front+Cardiovasc+Med%22%5BJournal%5D)">Low-voltage zones as the atrial fibrillation substrates: Relationship With initiation, perpetuation, and termination.</a> Front Cardiovasc Med. 8, 705510(2021).</li>
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<li>Hiram, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Resolution-promoting+autacoids+demonstrate+promising+cardioprotective+effects+against+heart+diseases%5BTitle%5D)+AND+%22Mol+Biol+Rep%22%5BJournal%5D)">Resolution-promoting autacoids demonstrate promising cardioprotective effects against heart diseases.</a> Mol Biol Rep. 49 (6), 5179-5197 (2022).</li>
<li>Hiram, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Cardiac+cytokine+therapy%3F+Relevance+of+targeting+inflammatory+mediators+to+combat+cardiac+arrhythmogenic+remodeling%5BTitle%5D)+AND+%22Int+J+Cardiol+Heart+Vasc%22%5BJournal%5D)">Cardiac cytokine therapy? Relevance of targeting inflammatory mediators to combat cardiac arrhythmogenic remodeling.</a> Int J Cardiol Heart Vasc. 37, 100918(2021).</li>
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</ol>

The authors have nothing to disclose.

The successful performance of the PAB is the most crucial part of this protocol. It is important to properly distinguish the aorta and the PA trunk. The isolation of the PA must be performed meticulously to avoid tearing, bleeding, and death during the procedure. The application of the suture around the 19G lead must be performed quickly and followed by immediate removal of the lead, to avoid too long &#39;complete obstruction&#39; of the PA due to the presence of the lead.
According to the requirements of the investigations, we determined that a 5-0 Silk was more stable than a metal clip to perform the PAB10,13. In addition, the 5-0 Silk allowed removal, while the clips provoked risks of tearing the PA. Researchers performing the PAB must adapt the choice of suture material (silk, metal, plastic clip) in accordance with their research objectives10.
In this study, the PAB (leaving 1 mm free diameter) was followed by in vivo analyses 3 weeks post-PAB. After 21 days, the mortality rate increased among the animals due to the severity of the right-sided cardiac remodeling10,13,23 (Figure 9). This protocol was designed and adapted for our exploration of arrhythmogenic cardiac remodeling in 3 weeks. Researchers reproducing this model can consider adapting the diameter using another lead than the 19 G and/or prolonging or decreasing the duration of post-PAB remodeling until euthanasia23.
The single-dose MCT injection is a recognized method to induce severe PAH and RHF8,9. However, due to the importance of MCT-induced pneumo-toxicity, this method was not relevant in our specific context, which aimed to study the impact of inflammation in RHF-induced CA9. The specific research hypothesis of this study required the use of a method of increased PA without pulmonary injury to avoid inflammation signaling originating from the lung. Hence, the PAB strategy was the best option in our context13.
This method can find applications in various research areas. In cardiology, the PAB protocol can be useful in studying right-sided cardiac hypertrophy, cardiac arrhythmogenesis, and valvular disorder (PA stenosis, tricuspid malfunction)24,25,26. In research on aging, the PAB protocol can be useful to evaluate the impact of RHF in the aggravation of age-related cardiac dysfunction27. In pulmonology, the PAB protocol can be used to study the impact of PA trunk stenosis on intra-pulmonary function28. Among other avenues, the PAB can also be useful to evaluate the role of long-standing PAB-induced RHF on brain function and neuro-degenerative disorders29. Overall, the impact of cardiac inflammation and fibrosis in heart-associated disorders is a major concern30. The PAB model of cardiac fibrosis and inflammation offers an interesting standardized and reproducible approach to evaluate the mechanisms associated with cardiac inflammation and the possibility of testing potential interventional strategies31,32.
Depending on the specificity of the model studied, researchers may prefer inducing other levels of RHF severity than the one described in this paper by using gauge needles different from the 19 G presented in the article. It is therefore important to notice that for smaller lead diameters, using 20 G or 21 G, we faced 100% mortality of rats weighing 225-275 g within minutes following the suture due to the obstruction of the PA trunk.
The PAB-induced RHF is a reproducible and efficient method to induce and study CA, including AF in rats. The atrial and ventricular remodeling provoked by the narrow PAB (1 mm diameter) is characterized by myocardial inflammation and fibrosis, which confers an interesting approach to investigating RHF-associated ventricular and atrial arrhythmogenesis.

Right heart failure (RHF) is characterized by right ventricular (RV) and atrial (RA) hypertrophy and dilation, leading to right-sided cardiac malfunction in response to chronic RV pressure overload due to the constriction of the pulmonary arteries (PA)1. Hence, conditions provoking the narrowing of PA can be responsible for an increased risk of RHF1,2,3,4. Clinical data revealed that RHF is the major cause of hospitalization (56%) in patients with PA hypertension (PAH)2. Clinical studies have shown that independent of the cause of PAH, including thromboembolic pulmonary hypertension (PH) and idiopathic PAH, patients are often affected by RHF and are 20% more susceptible to developing cardiac arrhythmias including supraventricular tachyarrhythmias and atrial fibrillation (AF)2,5,6.
To better understand the association between PAH and RHF, animal studies, including the model of a single dose of monocrotaline (MCT), have been used to provoke severe lung inflammation and RHF7,8. We recently observed that MCT-induced RHF was associated with RA inflammation and AF9. However, due to the importance of MCT-induced pulmonary inflammation and circulating cytokines, it was difficult to describe whether MCT-induced RA inflammation is a consequence of RHF only9. Hence, a new model of RHF-induced cardiac arrhythmia was required to study the RA inflammatory status.
The PA trunk banding (PAB) experimental model has been used in various animal species to mimic obstructive PA diseases and to study the associated pathological cardiac remodeling affecting the right side of the heart10. PAB has been reported as an effective method to induce right RV dysfunction and failure in various studies mimicking RV overload10,11,12,13,14,15,16. Technically, PAB is the placement of a permanent suture on the PA trunk, provoking a mechanical reduction of the PA trunk diameter10. PAB generates an increased pressure overload to the RV10. First, as a compensatory adaptation to the sudden increase in RV afterload, the RV cavity is dilated, leading to chronic RV hypertrophy10,13. RV dilation and hypertrophy affect the tricuspid valves, which become leaky13. More precisely, the pronounced dilation of the RV combined with high RV afterload has the effect of stretching the tricuspid valve annulus located between the RV and the RA13,17. Due to the incomplete occlusion of the valve, a portion of the blood ejected from the RV during systole will be directed toward the RA cavity17. Leakage of the tricuspid valve can be observed through echocardiography and is called tricuspid regurgitation17. Then, the RA receives inappropriately high blood pressure, contributing to increased RA dilation and hypertrophy13. The chronic RV and RA remodeling are accompanied by local myocardial inflammatory reactions leading to RV and RA fibrosis and loss of function9,13. Cardiac fibrosis is characterized by the development of low-voltage zones that are less contractile and more susceptible to provoking conduction block and re-entry circuits involved in the development of cardiac arrhythmias, including ventricular fibrillation and AF18,19.
The originality of this paper resides in the utilization of a standardized method of PAB-induced right-sided cardiac remodeling to provoke and study cardiac arrhythmias inducibility in 3 weeks post-PAB. The main advantages of this surgical approach are: i) the direct control over the reduction of the PA trunk diameter and ii) the avoidance of pulmonary inflammation to focus on RHF-induced myocardial inflammation to study cardiac arrhythmias, including AF.
The approach described here involves a precise microsurgical procedure to create the PAB, assessment of increased RV afterload, echocardiography to observe PAB-induced myocardial structural and functional remodeling, and electrophysiological study to evaluate vulnerability to cardiac arrhythmias, including AF.

<table><tbody><tr><td>0.9% Sodium Chlorine Injection USB (100 ml)&amp;nbsp;</td><td>Baxter</td><td>JB1302P</td><td>Solution used for drugs (analgesic and anti-inflammatory) dilution and for preparing saline water syringes dedicated to rehydrating the animal after the surgery</td></tr><tr><td>19 G x 1 1/2 PrecisionGlide Needle</td><td>BD</td><td>305187</td><td>Needle modified (bent and blunted) to be used as a spacer during for the partial constriction of the pulmonary trunk</td></tr><tr><td>2&quot; x 2&quot; Non Woven Non-Sterile Ritmed Gauze Sponge, 4-Ply</td><td>AMD-Ritmed</td><td>A2101-CH</td><td>Gauze sponges used to absorb blood from the wound or to gently push organs (ex: thymus) aside.</td></tr><tr><td>4&quot; x 4&quot; Non Woven Non-Sterile Ritmed Gauze Sponge, 4-Ply (x200)</td><td>AMD-Ritmed</td><td>A2100-CH</td><td>Gauze sponges used to absorb blood from the wound or to gently push organs (ex: thymus) aside.</td></tr><tr><td>5-0 Vicryl Violet Suture RB-1 1/2 Circle Needle 17mm 27&quot;</td><td>Ethicon</td><td>J303H</td><td>Synthetic absorbable sterile surgical suture with a taperpoint needle used for muscle and skin wounds closure.</td></tr><tr><td>Anafen (100 mg/mL)</td><td>Merial Canada, Inc.</td><td>1938126</td><td>Diluted injectable solution of ketoprofen administered as a nonsteroidal anti-inflammatory, analgesic and antipyretic drug.</td></tr><tr><td>AutoClip&amp;nbsp;System</td><td>FST</td><td>12020-00</td><td>Can be used to close the skin wound. Includes a clip applier, wound clips (9 mm) and a clip remover.</td></tr><tr><td>Dumont #5/45 Forceps</td><td>FST</td><td>11251-35</td><td>Dumoxel forceps with tips angled at 45&amp;deg;. Used to tighten the knots around the spacer placed on the pulmonary trunk.</td></tr><tr><td>Fine Scissors - Sharp</td><td>FST</td><td>14060-10</td><td>Stainless steel iris scissors dedicated to intercostal muscles incision and suture cutting.</td></tr><tr><td>Forane (Isoflurane) 100 mL</td><td>Baxter Canada</td><td>BAXCA2L9100</td><td>Inhalation anesthetic used for rodents during their PAB surgery.</td></tr><tr><td>IV Catheter 16 G x 1.77 &quot; (Straight)</td><td>BD Insyte</td><td>381257</td><td>Catheter used as an endotracheal tube with its metal stylet blunted.</td></tr><tr><td>Light&amp;nbsp; LED 130 F - DrMach</td><td>Eickemeyer</td><td>M130300</td><td>LED wall mounted light.</td></tr><tr><td>Magnetic Fixator Retraction System: Base plate</td><td>FST</td><td>18200-50</td><td>Metal plate on which the associated fixtures are installed. It is placed around the heating plate.</td></tr><tr><td>Magnetic Fixator Retraction System: Elastomer (2 m Roll)</td><td>FST</td><td>18200-07</td><td>Used to attach the retractors to the fixators.</td></tr><tr><td>Magnetic Fixator Retraction System: Fixators</td><td>FST</td><td>18200-02</td><td>Movable anchors that can be placed on the base plate.</td></tr><tr><td>Magnetic Fixator Retraction System: Retractors</td><td>FST</td><td>18200-11</td><td>Retractors allowing to maintain the surgical wound with the desired opening</td></tr><tr><td>Metzenbaum Scissors (Curved)</td><td>FST</td><td>14017-14</td><td>Stainless steel blunt scissors used for blunt dissection of the skin and muscles.</td></tr><tr><td>Micro-Adson Forceps</td><td>FST</td><td>11018-12</td><td>Stainless steel serrated forceps used to grasp skin and other tissues.</td></tr><tr><td>Oster Golden A5 2-Speed Clipper</td><td>Oster Professional</td><td>34264416949</td><td>Pet grooming clipper used to prepare the surgical field. Since it&#039;s meant to be used with large animals, the user needs to be careful with rats.</td></tr><tr><td>Rodent heating plate or warming system</td><td>Custom made</td><td>N/A</td><td>Plate connected to a unit equipped with a LED screen displaying the temperature detected by the rectal probe as well as the target temperature.</td></tr><tr><td>Rodent Ventilator Model 683</td><td>Harvard Apparatus</td><td>74240-2</td><td>Mechanical ventilator used for small laboratory animals (max 5 kg).</td></tr><tr><td>Semken Forceps with Serrations (Curved)</td><td>FST</td><td>11009-13</td><td>Stainless steel forceps used for tissue dissection.</td></tr><tr><td>Semken Forceps with Serrations (Straight)</td><td>FST</td><td>11008-13</td><td>Stainless steel forceps used for tissue dissection.</td></tr><tr><td>Silky Fresh Hair removal Cream</td><td>Veet</td><td>62200825036</td><td>Hair removal product used to prepare the surgical site after shaving.</td></tr><tr><td>Soluprep&amp;nbsp;</td><td>3M</td><td>103.26</td><td>Bottled antiseptic solution tinted with 2% chlorhexidine and 70 % alcohol 225 mL.</td></tr><tr><td>Stainless steel spatula 195 mm</td><td>Heathrow Scientific</td><td>HS15907</td><td>Spatula used as a tongue depressor during rat intubation.</td></tr><tr><td>Stereomicroscope System SZ61TR</td><td>Olympus</td><td>88-126</td><td>Microscope equipped with binoculars and a built-in camera allowing for video filming.</td></tr><tr><td>Sterile Sodium Chloride 0.9% Irrigation Bottle (60 mL)</td><td>Saline H2O</td><td>25-6048SA-L</td><td>Solution used to keep the wound moist throughout the surgery.</td></tr><tr><td>Surgical Scissors - Sharp-Blunt (Straight)</td><td>FST</td><td>14001-12</td><td>Stainless steel scissors used to make the initial skin incision.</td></tr><tr><td>Suture 5-0 Silk No Needle</td><td>Henry Schein</td><td>102-6344</td><td>Silk thread used to do the constriction of the pulmonary trunk</td></tr><tr><td>Systane Ointment</td><td>Alcon</td><td>2444062</td><td>Eyes lubricant providing a temporary relief of burning and irritation caused by the dryness of the eyes during surgery.</td></tr><tr><td>SZ2-STU2 stereomicroscope stand</td><td>Olympus</td><td>N1198900</td><td>The arm attached to the base provides a great freedom of movement to the microscope head.</td></tr><tr><td>Tissue forceps - 1X2 Teeth</td><td>FST</td><td>11021-15</td><td>Stainless steel forceps allowing to grasp, hold and manipulate tissues (skin and muscles).</td></tr><tr><td>Transpore Surgical Tape</td><td>3M</td><td>1527-1</td><td>Medical tape used to immobilized the rats&#039; forelimbs and hindlimbs.</td></tr><tr><td>Vetbond Tissue Adhesive (3 mL)</td><td>3M</td><td>1469SB</td><td>Surgical glue that can be applied in small amounts on the skin It can be used as a complement to subcutaneous sutures.</td></tr><tr><td>Vetergesic Multidose (0.3 mg/mL) 10 mL</td><td>Ceva Canada</td><td>2342510</td><td>Diluted injectable solution of buprenorphine administered as an analgesic drug.</td></tr><tr><td>Veterinary anesthesia evaporator Tec 4</td><td>Dispomed</td><td>34001 Iso</td><td>Enables vaporization of isoflurane and concentration at 0&amp;ndash;5%.</td></tr></tbody></table>

rat model of right-sided cardiac remodeling and arrhythmia using pulmonary artery banding

Rat Model of Right-Sided Cardiac Remodeling and Arrhythmia Using Pulmonary Artery Banding

Clinical conditions, including chronic obstructive pulmonary disease or pulmonary arterial hypertension (PAH), can lead to chronic right ventricle pressure overload and progressive right heart failure (RHF). RHF can be identified by right-sided cardiac hypertrophy and dilation associated with abnormal myocardial function affecting the RV and the right atrium (RA). We recently demonstrated that severe RHF is accompanied by an increased risk of atrial inflammation, atrial fibrosis, and atrial fibrillation (AF), the most common type of cardiac arrhythmia (CA). Recent studies have shown that RV and RA inflammation plays an important role in the arrhythmogenesis of CA, including AF. However, the impact of inflammation in the development of CA and AF in RHF is poorly described.
Experimental models of RHF are required to better understand the association between right-sided myocardial inflammation and CA. The rat model of monocrotaline (MCT)-induced pulmonary hypertension (PH) is well-established to provoke RHF. However, MCT triggers severe pneumo-toxicity and pulmonary inflammation. Hence, MCT-induced RHF does not help to distinguish whether the subsequent myocardial inflammation originates from the RHF per se or circulating inflammatory signals secreted by the injured lung.
In this article, a mechanical method involving pulmonary artery trunk banding (PAB) was used to provoke right-sided cardiac arrhythmogenesis. The PAB consists of performing a permanent suture of the pulmonary artery trunk for 3 weeks. Such an approach generates increased right-sided pressure overload. At D21 post-PAB, the suture results in hypertrophied, dilated, and inflamed RV and RA. The PAB-induced RHF is also accompanied by vulnerability to ventricular and atrial arrhythmias, including AF.

Visual confirmation of the appropriate ligation of the PA trunk during surgery 
During the PAB procedure, an indication of good positioning of the suture is an immediate augmentation of the blood pressure and prompt dilation of the RV and the root of the PA -trunk at the junction with the RV. The suture must not move to ensure a constant and permanent pressure overload for 3 weeks. In this study, the use of a 5-0 Silk was validated as more stable than a metal clip (Figure 2E,F). The 5-0 Silk also allows the possibility of removing the suture if required by a specific study design.
An important observation made during this study was that the application of metal clips resulted in random shapes of the free diameter around the 19 G lead, which is an important source of variability. In this study, a steady diameter of 1 mm was required. Moreover, removing the metal clips often resulted in tearing the PA trunk, which is not acceptable in a study design that would require the removal of the suture to evaluate the restoration of the normal pressure (Figure 2E,F).
Confirmation and measurement of PAB-induced right-sided ventricular pressure overload (Figure 4 and Figure 5) 
The ideal confirmation of the increased pressure post-PAB would be the hemodynamic measurement of the pressure with an intravenous and intracardiac catheter as described previously9. For protocols requiring preservation of the heart for a long period and non-invasive approaches, the above-described echocardiography methodology helped to assess the increase in blood velocity and pressure gradient around the suture using CW Doppler (Figure 4A,C). This non-invasive method even allowed the visualization of the ligation and the blood flow disruption caused by the narrowing of the artery diameter by the PAB (Figure 4B,C). Here are shown echocardiography data obtained at D21 post-PAB, but researchers applying this method can perform such non-invasive transthoracic echocardiography at various time points pre- and post-PAB, according to the requirements of their specific investigation and research objectives.
<img alt="Pulmonary artery Doppler echocardiography, sham vs. PAB; velocity, gradient, statistical analysis." class="xfigimg" src="/files/ftp_upload/67001/67001fig04.jpg" data-altupdatedat="1788304762000" data-alt="Figure 4"> 
Figure 4: Assessment of PA trunk ligation post-PAB. Continue wave Doppler in a 2D parasternal short axis view was used to visualize the flow pattern crossing the PA trunk in PAB compared to sham rats. (A) Measurement of the blood-flow velocity ejected from the RV through the PA trunk in a sham (left panel) and PAB rats (right panel). (B) Color-flow mapping of the PA trunk in sham (left panel) and PAB rat (right panel). The blood normally ejected from the RV and moving away from the heart with laminar flow appears in blue, and turbulent blood flow after the PAB due to the fixed RV outflow obstruction appears in red and yellow. The partial ligation of the PA trunk can be recognized on the right panel due to the opacity of the silk suture. (C) PA peak velocity expressed in cm/s in PAB compared to sham at D21 post-PAB. (D) Quantification of the PA mean gradient of pressure expressed in mmHg in PAB compared to sham at D21 post-PAB. (Statistical analyses: Data were normally distributed as assessed by the Shapiro-Wilk test. A comparison of the data was performed using the student's t-test. n = 6 rats per group. Results are expressed as mean ± S.E.M.) <a href="https://www.jove.com/files/ftp_upload/67001/67001fig04large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
On the right side of the heart, PAB induced a severe RHF confirmed by increased RV thickness and RA dilation accompanied by myocardial malfunction, as observed by echocardiography on D21 post-PAB. In terms of RV function, the RV systolic pressure was significantly increased in PAB rats compared to sham, and the in vivo echocardiography also revealed that the contractility rate (Sr) was decreased in PAB compared to sham (Figure 5A-C). Compared to sham rats, the RV dimension at end-diastole (RVDd) and the RV anterior wall thickness at end-diastole (RVAWd) were significantly increased. These echocardiography observations were confirmed after euthanasia and histological analysis of the transverse section of the heart from PAB rats compared to sham (Figure 5D). The increase in the volumetric capacity of the RV in response to the elevated afterload caused the interventricular septum to be pushed toward the LV, generating a relative compression of the LV (Figure 5A,D).
<img alt="Heart ultrasound and histology; RV, LV analysis; graphs of pressure, contractility; PAB vs. Sham." class="xfigimg" src="/files/ftp_upload/67001/67001fig05.jpg" data-altupdatedat="1788304762000" data-alt="Figure 5"> 
Figure 5: Confirmation of PAB-induced Right Ventricle Remodeling at D21 post-PAB. (A) 2D apical 4-chamber view of the four cardiac chambers highlighting the dilation of the RA and RV in PAB rats (right panel) compared to sham (left panel). Tissue Doppler imaging was used for (B) the quantification of the RV systolic pressure expressed in mmHg in PAB rats compared to sham and (C) the measurement of the RV lateral wall systolic contractility (Sr) expressed in cm/s in PAB rats compared to sham. (D) Histological pictures of transverse sections of the heart in the sham (left panel) and PAB rat (right panel) confirming that the PAB induced a significant enlargement of the RV compared to the sham. Scale bars: 5 mm. (Statistical analyses: Data were normally distributed as assessed by the Shapiro-Wilk test. A comparison of the data was performed using the student's t-test. n = 6 rats per group. Results are expressed as mean ± S.E.M.) <a href="https://www.jove.com/files/ftp_upload/67001/67001fig05large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
Assessment of PAB-induced right-sided atrial dilation and tricuspid regurgitation (Figure 6) 
The in vivo echocardiography performed at D21 post-PAB confirmed that the RADs significantly increased while the LADs was unchanged, because of the PAB-induced constant augmentation of pressure on the right side of the heart (Figure 5A, Figure 6A,B). The persistent PAB-induced right-sided pressure overload was accompanied by the deformation of the tricuspid valve annulus. PAB-induced malfunction of the tricuspid valve was assessed by in vivo echocardiography performed at D21 post-PAB, by the observation of tricuspid regurgitation characterized by blood leakage into the RA at systole (Figure 6C-E).
<img alt="RADs and LADs echocardiography; TAPSE and tricuspid velocity graph; pulmonary artery banding study." class="xfigimg" src="/files/ftp_upload/67001/67001fig06.jpg" data-altupdatedat="1788304762000" data-alt="Figure 6"> 
Figure 6: Evaluation of PAB-induced remodeling of the RA and tricuspid valve at D21 post-PAB. (A) Quantification of the RA dimension at end-systole (RADs) in sham and PAB rats measured by 2D apical 4-chamber view. (B) Quantification of the LA dimension at end-systole (LADs) in sham and PAB rats. (C) Color mapping on 2D apical 4-chamber view was recorded to observe normal closure of the tricuspid valve in sham (left panel) compared to tricuspid regurgitation characterized by blood leakage from the RV into the RA of PAB rats (right panel) in response to PAB-induced right-sided stretching and deformation of the tricuspid valve annulus. (D) M-mode echocardiography in apical 4-chamber view was used for the quantification of tricuspid annulus plane systolic excursion (TAPSE) in PAB rats compared to sham. (E) Pulsed wave Doppler was used for the quantification of the tricuspid annulus moving velocity in PAB rats compared to sham. (Statistical analyses: Data were normally distributed as assessed by the Shapiro-Wilk test. A comparison of data was performed with the Student's t-test. n = 6 rats per group. Results are expressed as mean ± S.E.M.) <a href="https://www.jove.com/files/ftp_upload/67001/67001fig06large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
Evaluation of PAB-induced cardiac arrhythmogenesis (Figure 7 and Figure 8) 
AB-induced cardiac remodeling was observable by electrophysiological analyses on D21 post-PAB. ECG parameters, including R-R interval, P-wave duration, and QT interval were significantly increased in PAB rats compared to sham (Figure 3A). These changes revealed that the heart rate, the atrial conduction, and the ventricular contractility were affected by the PAB (Figure 7).
In addition, compared to sham, PAB rats were significantly more vulnerable to cardiac arrhythmias, including AF, in response to electrical stimulations (Figure 8).
<img alt="Cardiac interval analysis; graphs comparing R-R, P-wave, P-R, QRS, QT intervals in Sham vs. PAB." class="xfigimg" src="/files/ftp_upload/67001/67001fig07.jpg" data-altupdatedat="1788304762000" data-alt="Figure 7"> 
Figure 7: Electrocardiogram analyses. ECG parameters (in ms) were measured, including (A) R-R interval, (B) P-wave duration, (C) P-R segment, (D) QRS complex, and (E) QT interval. (Statistical analysis: Data were normally distributed as assessed by the Shapiro-Wilk test. Comparisons were performed by Student's T-test. Each point represents an individual animal. n = 6 rats per group. Results are expressed as mean ± S.E.M.). <a href="https://www.jove.com/files/ftp_upload/67001/67001fig07large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="ECG analysis with stimulation impact; graphs showing atrial fibrillation inducibility, duration comparison." class="xfigimg" src="/files/ftp_upload/67001/67001fig08.jpg" data-altupdatedat="1788304762000" data-alt="Figure 8"> 
Figure 8: PAB-induced cardiac arrhythmias, including AF. (A) Representative surface ECG observed in sham (upper panel) and PAB rats (lower panel) during electrophysiological study showing sinus rhythm (SR), 3-second burst pacing (stimulation) followed by AF or/and SR recovery. (B) Quantification of PAB-induced vulnerability to atrial tachyarrhythmias, including AF and atrial flutter (AFl). (C) Duration of AF in inducible sham and PAB rats. (Statistical analyses: (B) Fisher's exact text. (C) n was too short in sham to perform a comparison test. n = 6 rats per group. Results are expressed as mean ± S.E.M.) <a href="https://www.jove.com/files/ftp_upload/67001/67001fig08large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
Mortality (Figure 9) 
The placement of the suture at D0 was accompanied by a 30% mortality among PAB versus 0% in sham rats in the minutes to D3 following the surgery. Rats who survived the first 3 days post-surgery survived until the day of final experiments (D21). After D21, the mortality rate increased significantly among PAB rats (60% versus 0% in sham) due to the severity of the right-sided remodeling and RHF (Figure 9).
<img alt="Mortality rate bar graph comparing sham vs PAB post-surgery survival rates with statistical notation." class="xfigimg" src="/files/ftp_upload/67001/67001fig09.jpg" data-altupdatedat="1788304762000" data-alt="Figure 9"> 
Figure 9: Mortality rate. Mortality expressed in percent (%) in sham and PAB rats between D0 and D3, D4 and D21, and after D21 post-surgery. <a href="https://www.jove.com/files/ftp_upload/67001/67001fig09large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>

Right heart failure (RHF) is characterized by right-sided cardiac dilation and hypertrophy, leading to ventricular and atrial malfunction. Cardiopulmonary conditions associated with RHF are accompanied by an increased risk for cardiac arrhythmias. This article describes a standardized model of pulmonary artery banding-induced RHF associated with enhanced ventricular and atrial arrhythmogenesis.

Clinical conditions, including chronic obstructive pulmonary disease or pulmonary arterial hypertension (PAH), can lead to chronic right ventricle ...

rat-model-right-sided-cardiac-remodeling-arrhythmia-using-pulmonary

Research

JoVE Journal

Medicine

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