Key result
Long-term volume load induced by aorto-caval shunt in rats led to overt clinical signs of end-stage right ventricular failure at 6 months, but was not associated with myocardial fibrosis or increased pro-fibrotic signaling.
Why the study?
The importance of myocardial fibrosis in right ventricular failure has been challenged, and whether it drives the transition from compensated to decompensated volume load-induced RV dysfunction remains unclear.
Does myocardial fibrosis drive the transition from compensated to decompensated volume load-induced right ventricular dysfunction in rats?
Does myocardial fibrosis drive the transition from compensated to decompensated volume load-induced right ventricular dysfunction in rats?
In a rat model of volume load-induced right ventricular failure, the transition to decompensated RV dysfunction is not associated with the development of myocardial fibrosis or pro-fibrotic signaling.
Animal data question fibrosis as driver of RV decompensation; leaves open translation to human volume-overload phenotypes.
BACKGROUND: Right 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. METHODS: = 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. RESULTS: At 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. CONCLUSIONS: In 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.
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Hagdorn et al. (2021) studied Volume load-induced right ventricular failure (n=37). Aorto-caval shunt (ACS) surgery vs. Sham surgery was evaluated on Myocardial fibrosis and clinical signs of RV failure. Long-term volume load induced by aorto-caval shunt in rats led to overt clinical signs of end-stage right ventricular failure at 6 months, but was not associated with myocardial fibrosis or increased pro-fibrotic signaling.
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