Name: chronic ovine model of right ventricular failure and functional tricuspid regurgitation
Uploaded: 2023-03-17T13:40:00
Description: Watch this Scientific Journal Video about Chronic Ovine Model of Right Ventricular Failure and Functional Tricuspid Regurgitation at JoVE.com

The study was funded by an internal grant from the Meijer Heart and Vascular Institute at Spectrum Health.

The protocol was approved by the Michigan State University Institutional Animal Care and Use Committee (IACUC) (Protocol 2020-035, approved on 7/27/2020). For this study, 20 adult male sheep weighing 62 &#177; 7 kg were used.
1. Preoperative steps
<ol>
	<li>Fast the animal 12 h prior to surgery (overnight).</li>
	<li>Place the animal in a sheep chair (Figure 1), and prepare for the right jugular vein cannulation using a long 11 Fr introducer she...

<ol>
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(173), e62694 (2021).</li><li>Dufva, M. 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In this model, 8 weeks of pulmonary artery banding resulted in a stable chronic ovine model of right ventricular dysfunction and, in most cases, significant FTR. The strengths of the presented chronic PAB model include the precise afterload adjustment during the procedure, although its influence on RV responses may differ. The model is suitable for evaluating varying degrees of RV failure or FTR, with the severity modulated by the degree of pulmonary artery constriction. Moreover, the application of fixed and stable resi...

Right ventricular failure (RVF) is recognized as an important factor contributing to the morbidity and mortality of cardiac patients. The most common causes of RVF are left-sided heart disease and pulmonary hypertension1. During the progression of RVF, functional tricuspid regurgitation (FTR) may arise as a consequence of right ventricular (RV) dysfunction, annular dilatation, and subvalvular remodeling. Moderate to severe FTR is an independent predictor of mortality2,3, and it is estimated that 80%-90% of tricuspid regurgitation cases are functional in nature4. FTR itself may promote adverse ventricular remodeling by influencing either afterload or preload5. The tricuspid valve has historically been considered the forgotten valve6, and it was believed that the treatment of left-sided heart disease would resolve the associated RV pathology and FTR7. Recent data have shown this to be a faulty strategy, and current clinical guidelines advocate a much more aggressive approach to FTR4. However, the pathophysiology of severe FTR associated with right ventricular dysfunction is still poorly understood, leading to suboptimal clinical results8. The currently available large animal models of RVF are based on pressure, volume, or mixed overload. We have previously described a large animal model of RVF and TR but only in an acute setting9.
The current study focuses on a chronic ovine model of pulmonary artery banding (PAB) to increase RV afterload (pressure overload) and induce RV dysfunction and FTR. The afterload model is reliable and reproducible compared to pulmonary hypertension models, in which changes in microvasculature are less predictable and more likely10. The goal of the study was to develop a chronic large animal model of RVF and FTR that would most accurately mimic RV pressure overload in patients with left-sided heart disease and pulmonary hypertension. The establishment of such a model would permit in-depth studies on the pathophysiology of the ventricular and valvular remodeling associated with RV dysfunction and tricuspid insufficiency. The ovine model was chosen based on our prior work on the mitral valve and the published literature supporting the anatomical and physiological similarities between human and ovine hearts11,12,13.
For this study, 20 adult sheep (62 &#177; 7 kg) underwent a left thoracotomy and main pulmonary artery banding (PAB) to at least double the systolic pulmonary artery pressure (SPAP), thus inducing RV pressure overload. The animals were followed for 8 weeks, and the symptoms of heart failure were treated with diuretics when clinically apparent. Surveillance echocardiography was performed periodically to assess RV function and valvular competence. Following the completion of the experimental protocol for model development (8 weeks), the animals were taken back to the operating room for median sternotomy and the implantation of sonomicrometry crystals on the epicardial and intra-cardiac structures. This procedure was performed using cardiopulmonary bypass with the heart beating and with bicaval control. There were no problems in weaning the animals from the cardiopulmonary bypass or acquiring the sonomicrometry data in a stable steady-state hemodynamic environment without the need for inotropes for right heart support. We anticipate performing tricuspid ring annuloplasty and other right heart procedures in the near future using a right thoracotomy approach in both terminal and survival experiments. The current experience leads us to believe that it will be possible to wean the animals from the cardiopulmonary bypass without difficulty and that long-term survival is feasible. As such, we believe the model will permit the performance of clinically pertinent cardiac procedures. Below is a description of the steps (perioperative and operative) performed for carrying out the ovine experimental protocol.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Anesthesia Machine Drager Narkomed MRI-2</td>
			<td>Drager</td>
			<td>4116091-001</td>
			<td></td>
		</tr>
		<tr>
			<td>angiocatheter</td>
			<td>BD</td>
			<td>BD382268</td>
			<td>14GAx8.25cm</td>
		</tr>
		<tr>
			<td>BD ChloraPrep Scrub Teal 26 ml applicator with a sterile solution</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Blade #11</td>
			<td>Bard-Parker</td>
			<td>371111</td>
			<td></td>
		</tr>
		<tr>
			<td>Buprenorphine&#160;</td>
			<td>HIKMA</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>cefazolin 1.0g</td>
			<td>Hikma</td>
			<td>0143-9924-90</td>
			<td></td>
		</tr>
		<tr>
			<td>Diprivan 200mg/20ml</td>
			<td>63323-0269-29</td>
			<td>FRESENIUS KABI</td>
			<td></td>
		</tr>
		<tr>
			<td>Electrosurgical generator Valleylab Force FX</td>
			<td>Valleylab</td>
			<td>CF5L44233A</td>
			<td></td>
		</tr>
		<tr>
			<td>Gentamicin Sulfate 40 mg / mL</td>
			<td>Fresenius</td>
			<td>406365</td>
			<td></td>
		</tr>
		<tr>
			<td>i-Stat Blood analyzer MN 300</td>
			<td>Abbott</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Lidocaine HCl 1%</td>
			<td>Pfizer</td>
			<td>243243</td>
			<td></td>
		</tr>
		<tr>
			<td>Open ligating clip appliers Horizon Medium</td>
			<td>Teleflex</td>
			<td>237061</td>
			<td></td>
		</tr>
		<tr>
			<td>PERMAHAND Silk Suture</td>
			<td>PERMA HAND</td>
			<td>SA 63H</td>
			<td></td>
		</tr>
		<tr>
			<td>Pinnacle Introducer sheath</td>
			<td>Terrumo</td>
			<td>RSS102</td>
			<td>sheath length 10cm</td>
		</tr>
		<tr>
			<td>Prolene 3-0</td>
			<td>ETHICON</td>
			<td>8684H</td>
			<td></td>
		</tr>
		<tr>
			<td>Titanium Clips Medium</td>
			<td>Teleflex</td>
			<td>2200</td>
			<td></td>
		</tr>
		<tr>
			<td>Umbilical tape</td>
			<td>Ethicon</td>
			<td>EFA 1165</td>
			<td></td>
		</tr>
		<tr>
			<td>VICRYL 2 coated undyed 1X54&#34; TP-1</td>
			<td>ETHICON</td>
			<td>J 880T</td>
			<td></td>
		</tr>
		<tr>
			<td>Vicryl 2-0</td>
			<td>ETHICON</td>
			<td>J269H</td>
			<td></td>
		</tr>
	</tbody>
</table>

chronic ovine model of right ventricular failure and functional tricuspid regurgitation

The pathophysiology of severe functional tricuspid regurgitation (FTR) associated with right ventricular dysfunction is poorly understood, leading to suboptimal clinical results. We set out to establish a chronic ovine model of FTR and right heart failure to investigate the mechanisms of FTR. Twenty adult male sheep (6-12 months old, 62 &#177; 7 kg) underwent a left thoracotomy and baseline echocardiography. A pulmonary artery band (PAB) was placed and cinched around the main pulmonary artery (PA) to at least double the systolic pulmonary artery pressure (SPAP), inducing right ventricular (RV) pressure overload and signs of RV dilatation. PAB acutely increased the SPAP from 21 &#177; 2 mmHg to 62 &#177; 2 mmHg. The animals were followed for 8 weeks, symptoms of heart failure were treated with diuretics, and surveillance echocardiography was used to assess for pleural and abdominal fluid collection. Three animals died during the follow-up period due to stroke, hemorrhage, and acute heart failure. After 2 months, a median sternotomy and epicardial echocardiography were performed. Of the surviving 17 animals, 3 developed mild tricuspid regurgitation, 3 developed moderate tricuspid regurgitation, and 11 developed severe tricuspid regurgitation. Eight weeks of pulmonary artery banding resulted in a stable chronic ovine model of right ventricular dysfunction and significant FTR. This large animal platform can be used to further investigate the structural and molecular basis of RV failure and functional tricuspid regurgitation.

Following the completion of the experimental protocol for model development (nearly 8 weeks), the animals were taken back to the operating room for median sternotomy and the implantation of sonomicrometry crystals on the epicardial and intra-cardiac structures. This procedure was performed using cardiopulmonary bypass with the heart beating and with bicaval control, as&#160;described by our group in detail previously9. There were no problems in weaning the animals from the cardiopulmonary bypass o...

Watch this Scientific Journal Video about Chronic Ovine Model of Right Ventricular Failure and Functional Tricuspid Regurgitation at JoVE.com

Chronic Ovine Model of Right Ventricular Failure and Functional Tricuspid Regurgitation

Right ventricular failure and functional tricuspid regurgitation are associated with left-sided heart disease and pulmonary hypertension, which contribute significantly to morbidity and mortality in patients. Establishing a chronic ovine model to study right ventricular failure and functional tricuspid regurgitation will help in understanding their mechanisms, progression, and possible treatments.

The pathophysiology of severe functional tricuspid regurgitation (FTR) associated with right ventricular dysfunction is poorly understood, leading to ...

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