Long-Term Effects of Right Ventricular Pressure and Volume Overload: A Comparative Analysis in an Ovine Model

Vollständiger Abstract

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Background/Objectives: Pressure overload (PO) and volume overload (VO) represent important mechanisms underlying right ventricular (RV) failure; however, long-term comparative data regarding their distinct pathophysiological consequences remain limited. This study aimed to compare the long-term effects of PO versus VO in a large animal model. Methods: Juvenile sheep were randomly assigned to either a PO group (n = 7) or a VO group (n = 8). PO was induced by pulmonary artery banding, whereas VO was induced by pulmonary leaflet perforation (n = 4) or transannular patch (TAP) reconstruction (n = 4). Both VO procedures resulted in moderate-to-severe pulmonary regurgitation with comparable acute hemodynamic profiles and were therefore analyzed as a single VO group for the long-term assessment. Six animals from each group completed the follow-up period. Animals were evaluated preoperatively and at one-year follow-up using invasive hemodynamic monitoring, blood gas analysis, and echocardiography, followed by postmortem histological analysis of the myocardium. Results: Both models resulted in significant reductions in stroke volume index, cardiac index, RV stroke work index, ScvO2 and tricuspid annular plane systolic excursion (TAPSE). Similarly, the TAPSE/RV systolic pressure (RVSP) ratio decreased in both groups but was significantly lower in the PO group than in the VO group (p = 0.0022). Moreover, PO showed more pronounced RV diastolic dysfunction, characterized by a significant increase in right atrial pressure from baseline (p = 0.0313) and higher RV diastolic pressure compared to VO (p = 0.0065). In contrast, VO showed a greater impact on left ventricular (LV) geometry and diastolic filling, evidenced by reduced transmitral filling (p = 0.0313) and a lower indexed LV internal diameter compared to PO (p = 0.0411). Histological analysis revealed myocardial hypertrophy and fibrosis in both groups, as well as clusters of multinucleated cardiomyocyte-like cells showing preferential ventricular distribution according to overload physiology. Conclusions: Chronic PO and VO induced distinct phenotypes of RV dysfunction with differential ventricular adaptation and remodelling patterns.