Large animal model of acute right ventricular failure with functional tricuspid regurgitation

Abstract

BackgroundFunctional tricuspid regurgitation (FTR) commonly arises secondary to conditions affecting the left heart and is associated with right ventricular dysfunction and tricuspid annular dilatation. We set out to establish an animal model of acute RV failure (RVF) with FTR resembling the clinical features. MethodsTen adult sheep had pressure sensors placed in the LV, RV, and right atrium while sonomicrometry crystals were implanted around tricuspid annulus and on the RV. Animals were studied open-chest to assess for RV function and FTR after: (1) volume infusion, (2) pulmonary artery constriction, (3) 5 min posterior descending artery occlusion, and (4) combination of all interventions. Hemodynamic, echocardiographic, and sonomicrometry data were collected at baseline and after every intervention. RV dimensions, RV strain, and annular area, perimeter, and size were calculated from crystal coordinates. The model was validated in six additional sheep studied only before and after combined interventions. ResultsNeither volume infusion, pulmonary hypertension, nor ischemia were associated with RVF or clinically significant TR when applied separately but combined resulted in RVF and greater than moderate FTR. In the validation group, maximal RV volume increased (62 ± 14 vs 70 ± 16 ml, p = 0.006), contractility decreased (20 ± 6 vs 12 ± 2%, p = 0.02), and strain increased. FTR increased from 0.4 ± 0.5 to 2.5 ± 0.8 (p < 0.001) and annular area from 652 ± 87 mm2 to 739 ± 87 mm2 (p = 0.005). ConclusionsThe developed ovine model of acute RVF was associated with significant annular and RV enlargement and FTR. This novel and clinically pertinent research platform offers insight into the acute RVF pathophysiology and can be utilized to evaluate treatment interventions.