Abstract
BackgroundRight ventricular (RV) function and failure are key determinants of morbidity and mortality in various cardiovascular diseases. Myocardial fibrosis is regarded as a contributing factor to heart failure, but its importance in RV failure has been challenged. This study aims to assess whether myocardial fibrosis drives the transition from compensated to decompensated volume load-induced RV dysfunction.MethodsWistar rats were subjected to aorto-caval shunt (ACS, n = 23) or sham (control, n = 15) surgery, and sacrificed after 1 month, 3 months, or 6 months. Echocardiography, RV pressure-volume analysis, assessment of gene expression and cardiac histology were performed.ResultsAt 6 months, 6/8 ACS-rats (75%) showed clinical signs of RV failure (pleural effusion, ascites and/or liver edema), whereas at 1 month and 3 months, no signs of RV failure had developed yet. Cardiac output has increased two- to threefold and biventricular dilatation occurred, while LV ejection fraction gradually decreased. At 1 month and 3 months, RV end-systolic elastance (Ees) remained unaltered, but at 6 months, RV Ees had decreased substantially. In the RV, no oxidative stress, inflammation, pro-fibrotic signaling (TGFβ1 and pSMAD2/3), or fibrosis were present at any time point.ConclusionsIn the ACS rat model, long-term volume load was initially well tolerated at 1 month and 3 months, but induced overt clinical signs of end-stage RV failure at 6 months. However, no myocardial fibrosis or increased pro-fibrotic signaling had developed. These findings indicate that myocardial fibrosis is not involved in the transition from compensated to decompensated RV dysfunction in this model.
Highlights
Right ventricular (RV) function and failure are key determinants of morbidity and mortality in various cardiovascular diseases
In pulmonary hypertension (PH), increased RV pressure load leads to rapid RV deterioration and failure (Zijlstra et al, 2014), whereas RV volume loading in patients with repaired tetralogy of Fallot (rTOF) is generally tolerated for decades until eventually failure occurs (Kuehne et al, 2003; Bouzas et al, 2005)
To assess whether myocardial fibrosis drives the transition from compensated to decompensated volume load-induced RV dysfunction, this study aimed to describe the temporal pattern of ventricular adaptation, fibrosis and pro-fibrotic signaling in a long-term model of volume load induced RV failure
Summary
Right ventricular (RV) function and failure are key determinants of morbidity and mortality in various cardiovascular diseases. When exposed to chronic abnormal loading conditions, as is often the case in patients with congenital heart disease, deterioration of RV function and progression toward failure can occur (Friedberg and Reddy, 2019). Abnormal loading conditions consist either of increased pressure load, for example in the case of pulmonary hypertension (PH), or increased volume load, for example, in the case of pulmonary regurgitation in repaired tetralogy of Fallot (rTOF). Both types of ventricular loading induce very distinct phenotypes This study aims to assess whether myocardial fibrosis drives the transition from compensated to decompensated volume load-induced RV dysfunction
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