Abstract
Right ventricular (RV) failure is a major cause of mortality in acute or chronic lung disease and left heart failure. The objective of this study was to demonstrate a percutaneous approach to study biventricular hemodynamics in murine models of primary and secondary RV pressure overload (RVPO) and further explore biventricular expression of two key proteins that regulate cardiac remodeling: calcineurin and transforming growth factor beta 1 (TGFβ1).MethodsAdult, male mice underwent constriction of the pulmonary artery or thoracic aorta as models of primary and secondary RVPO, respectively. Conductance catheterization was performed followed by tissue analysis for changes in myocyte hypertrophy and fibrosis.ResultsBoth primary and secondary RVPO decreased biventricular stroke work however RV instantaneous peak pressure (dP/dtmax) and end-systolic elastance (Ees) were preserved in both groups compared to controls. In contrast, left ventricular (LV) dP/dtmax and LV-Ees were unchanged by primary, but reduced in the secondary RVPO group. The ratio of RV:LV ventriculo-arterial coupling was increased in primary and reduced in secondary RVPO. Primary and secondary RVPO increased RV mass, while LV mass decreased in primary and increased in the secondary RVPO groups. RV fibrosis and hypertrophy were increased in both groups, while LV fibrosis and hypertrophy were increased in secondary RVPO only. RV calcineurin expression was increased in both groups, while LV expression increased in secondary RVPO only. Biventricular TGFβ1 expression was increased in both groups.ConclusionThese data identify distinct effects of primary and secondary RVPO on biventricular structure, function, and expression of key remodeling pathways.
Highlights
Right ventricular (RV) failure is a major determinant of morbidity and mortality for millions of individuals worldwide who suffer from pulmonary hypertension (PH) due to acute and chronic lung disease, or left heart failure [1,2,3]
No significant difference in RV pressure was observed after 7 days of secondary RV pressure overload (RVPO) (Figure S1A)
RV end-diastolic volume was significantly increased in 7day primary RVPO only, while end-systolic volume was increased in both 7-day primary and 10-week secondary RVPO compared to sham controls
Summary
Right ventricular (RV) failure is a major determinant of morbidity and mortality for millions of individuals worldwide who suffer from pulmonary hypertension (PH) due to acute and chronic lung disease, or left heart failure [1,2,3]. Several studies have confirmed that elevated pulmonary artery systolic pressures are inversely associated with RV systolic function in both primary and secondary PH [4,5]. Ventriculo-arterial coupling describes the impact of arterial loading conditions on ventricular function. Optimal pump efficiency is achieved if ventricular function, or end-systolic elastance (Ees), is matched by vascular load, known as arterial elastance (Ea) [6,7,8,9,10]. Under conditions of RV pressure overload (RVPO) within an intact pericardium, reduced
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