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Hagdorn, Q.A.J.; Kurakula, K.; Koop, A.M.C.; Bossers, G.P.L.; Mavrogiannis, E.; Leusden, T. van; ... ; Berger, R.M.F. (2021)

Volume load-induced right ventricular failure in rats is not associated with myocardial fibrosis

Article / Letter to editor
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.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...Show moreBackground 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.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 (TGF beta 1 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.Show less
right ventricular remodeling
right ventricular remodeling and fibrosis
right ventricular failure
fibrosis
volume load
aortocaval shunt
tetralogy of Fallot
All authors
Hagdorn, Q.A.J.; Kurakula, K.; Koop, A.M.C.; Bossers, G.P.L.; Mavrogiannis, E.; Leusden, T. van; Feen, D.E. van der; Boer, R.A. de; Goumans, M.J.T.H.; Berger, R.M.F.
Date
2021-02-26
Journal
Frontiers in Physiology
Volume
12
DOI
doi:10.3389/fphys.2021.557514
Link
https://www.frontiersin.org/articles/10.3389/fphys.2021.557514/pdf