Volume Load-Induced Right Ventricular Failure in Rats Is Not Associated With Myocardial Fibrosis
Open Access
- 26 February 2021
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Physiology
Abstract
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: Wistar 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. 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.Keywords
This publication has 50 references indexed in Scilit:
- FHL2 Protein Is a Novel Co-repressor of Nuclear Receptor Nur77Published by Elsevier BV ,2011
- Extracellular Signal-Regulated Kinases 1 and 2 Regulate the Balance Between Eccentric and Concentric Cardiac GrowthCirculation Research, 2011
- Differential Cardiac Remodeling in Preload Versus AfterloadCirculation, 2010
- Passive Stiffness of Myocardium From Congenital Heart Disease and Implications for DiastoleCirculation, 2010
- Structural analysis of four and half LIM protein-2 in dilated cardiomyopathyBiochemical and Biophysical Research Communications, 2007
- The Failing Heart — An Engine Out of FuelNew England Journal of Medicine, 2007
- Calcineurin/NFAT Coupling Participates in Pathological, but not Physiological, Cardiac HypertrophyCirculation Research, 2004
- Different Growth Factor Activation in the Right and Left Ventricles in Experimental Volume OverloadHypertension, 2004
- Effects of Pulmonary Insufficiency on Biventricular Function in the Developing Heart of Growing SwineCirculation, 2003
- The L45 loop in type I receptors for TGF‐β family members is a critical determinant in specifying Smad isoform activationFEBS Letters, 1998