A novel porcine model for right ventricular dilatation by external suture plication of the pulmonary valve leaflets – practical and reproducible☆

Abstract

The right ventricle (RV) tolerates acute pulmonary valvular regurgitation fairly well, however, in the long-term dilatation and failure often ensues. There is little known of the structural and functional myocardial alterations following this pathophysiology, and therefore animal models are sought. We aimed to develop an animal experimental model for RV dilatation emphasizing feasibility, reproducibility and human compatibility. Free pulmonary valve insufficiency and RV dilatation were created with a novel external suture plication technique in nine 5 kg piglets. Six matched animals served as controls. After 10 weeks cardiac dimensions and physiology were assessed with in vivo cardiovascular MRI and conductance technique. RV end-diastolic volume increased 31% in the intervention group (P=0.03). The regurgitation fraction was 37% in the intervention group compared to -2% in controls (P<0.001). Conductance measurements showed preserved RV contractile function, but significant left ventricular diastolic impairment. This study is the first to show that pulmonary valve regurgitation, RV dilatation and functional impairment can be achieved by external leaflet plication. Compared to known methods, the advantages of this model are: 1) no induction of stenosis over time, 2) no risk of stent migration, and 3) very simple and reproducible.

Acute and Chronic Effects of Dysfunction of Right Ventricular Outflow Tract Components on Right Ventricular Performance in a Porcine Model

“…In contrast with other animal models addressing the RV properties after chronic PI (8,9), a decreased RV contractile state was noted after isolated PI at baseline conditions. Although contractility indices were lower at rest, contractile reserve only seemed to be impaired during dobutamine stress testing in these studies.…”

“…The chronic effects of pulmonary insufficiency-related volume overload on RV function have already been studied in animal models (7)(8)(9). Kuehne et al (8) demonstrated impaired biventricular systolic function and decreased RV contractility in growing swine, in relation to pulmonary insufficiency, through transcatheter stent implantation across the PV.…”

Effects of milrinone and epinephrine or dopamine on biventricular function and hemodynamics in right heart failure after pulmonary regurgitation

“…Dopamine-treated animals had a greater vasopressor effect in both the systemic and pulmonary circulation. Following 11 wk of PR, the classical features of right heart failure secondary to volume overload were pronounced, with right ventricular dilatation (4 -6, 10, 19, 20, 24, 27), decreased RV contractility (20), reduced compliance (2)(3)(4)20), a leftward septal shift in the diastolic phase, and compromised LV pressure generation (1,19). The degree of change in RV EDVI and LV EDVI was close to what have been described as the difference in healthy adults and patients with repaired tetralogy of Fallot (28).…”

Physiologic and molecular characterization of a murine model of right ventricular volume overload

“…Much less is known about the mechanisms of LV remodeling secondary to chronic volume overload (7,17,25,29,31,38,42). There are less data available in the volume overloaded RV (3), and only one prior study in a large animal model (1). Although the response of the RV and LV to afterload stress has many similarities, there are also important differences related to different embryologic precursors and differences in global structure, cell signaling, and calcium handling in response to hemodynamic loading (4,19,20,22,26,36).…”