Chronic Ovine Model of Right Ventricular Failure and Functional Tricuspid Regurgitation

Summary

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.

Abstract

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 ± 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 ± 2 mmHg to 62 ± 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.

Introduction

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 mortality^2,3, and it is estimated that 80%-90% of tricuspid regurgitation cases are functional in nature⁴. ....

Protocol

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 ± 7 kg were used.

1. Preoperative steps

1. Fast the animal 12 h prior to surgery (overnight).
2. Place the animal in a sheep chair (Figure 1), and prepare for the right jugular vein cannulation using a long 11 Fr introducer sheath (sheath length = 10 cm).
3. Shave with clippers along the IV placement site-the right anterior aspect of the neck around 10-15 cm lateral f....

Results

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 described by our group in detail previously⁹. There were no problems in weaning the animals from the cardiopulmonary bypass or acq.......

Discussion

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.......

Materials

List of materials used in this article

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