Time dependent changes in cytoplasmic proteins of the right ventricle during prolonged pressure overload (original) (raw)
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Right ventricular plasticity in a porcine model of chronic pressure overload
The Journal of Heart and Lung Transplantation, 2014
BACKGROUND: Ventricular-arterial coupling is a measure of the relationship between ventricular contractility and afterload. We sought to determine the relationship between ventricular-arterial coupling and right ventricular (RV) remodeling in a novel porcine model of progressive pulmonary hypertension (PH). METHODS: Chronic PH was induced in pigs by ligation of the left pulmonary artery (PA) followed by 5 weekly injections of cyanoacrylate to progressively obstruct the right lower lobe arteries (PH group, n ¼ 10). At 6 weeks, 5 PH animals underwent reperfusion of the left lung through conduit anastomosis to decrease RV afterload, whereas 5 other animals received no treatment. Five sham-operated piglets were used as controls. RV function was assessed using echocardiography and conductance catheterization. RV gene expression of beta-myosin heavy chain (β-MHC) and B-type natriuretic peptide (BNP) were quantified by polymerase chain reaction. RESULTS: At 6 weeks, compared with controls, the PH group had higher mean PA pressure (32 Ϯ 6 vs 14 Ϯ 2 mm Hg, p o 0.01). The increase in RV elastance was insufficient to compensate for the increase in pulmonary arterial elastance in the PH group and altered ventricular-arterial coupling occurred (0.65 Ϯ 0.16 vs 1.28 Ϯ 0.14, p o 0.01). The degree of ventricular-arterial uncoupling was related to RV enlargement and systolic dysfunction. Ventricular-arterial uncoupling and increased RV mass index were associated with up-regulation of β-MHC and BNP expression. CONCLUSIONS: Ventricular-arterial coupling is closely associated with ventricular remodeling and systolic function as well as contractile and BNP gene expression. Dynamic changes in myosin expression may determine RV work efficiency in PH.
Journal of Anatomy, 2008
Myocardial hyperplasia is generally considered to occur only during fetal development. However, recent evidence suggests that this type of response may also be triggered by cardiac overload after birth. In congenital heart disease, loading conditions are frequently abnormal, thereby affecting ventricular function. We hypothesized that chronic right ventricular pressure overload imposed on neonatal hearts initiates a hyperplastic response in the right ventricular myocardium. To test this, young lambs (aged 2-3 weeks) underwent adjustable pulmonary artery banding to obtain peak right ventricular pressures equal to left ventricular pressures for 8 weeks. Transmural cardiac tissue samples from the right and left ventricles of five banded and five age-matched control animals were studied. We found that chronic right ventricular pressure overload resulted in a twofold increase in right-to-left ventricle wall thickness ratio. Morphometric right ventricular myocardial tissue analysis revealed no changes in tissue composition between the two groups; nor were right ventricular myocyte dimensions, relative number of binucleated myocytes, or myocardial DNA concentration significantly different from control values. In chronic pressure overloaded right ventricular myocardium, significantly ( P < 0.01) more myocyte nuclei were positive for the proliferation marker proliferating cellular nuclear antigen than in control right ventricular myocardium. Chronic right ventricular pressure overload applied in neonatal sheep hearts results in a significant increase in right ventricular free wall thickness which is primarily the result of a hyperplastic myocardial response.
The Right Ventricle Under Pressure
Chest, 2009
Pulmonary arterial hypertension (PAH) is a deadly disease in which vasoconstriction and vascular remodeling both lead to a progressive increase in pulmonary vascular resistance. The response of the right ventricle (RV) to the increased afterload is an important determinant of patient outcome. Little is known about the cellular and molecular mechanisms that underlie the transition from compensated hypertrophy to dilatation and failure that occurs during the course of the disease. Moreover, little is known about the direct effects of current PAH treatments on the heart. Although the increase in afterload is the first trigger for RV adaptation in PAH, neurohormonal signaling, oxidative stress, inflammation, ischemia, and cell death may contribute to the development of RV dilatation and failure. Here we review cellular signaling cascades and gene expression patterns in the heart that follow pressure overload. Most data are derived from research on the left ventricle, but where possible specific information on the RV response to pressure overload is provided. This overview identifies the gaps in our understanding of RV failure and attempts to fill them, when possible. Together with the online supplement, it provides a starting point for new research and aims to encourage the pulmonary hypertension research community to direct some of their attention to the RV, in parallel to their focus on the pulmonary vasculature.
European Journal of Heart Failure, 2011
Right ventricular (RV) dysfunction is a major determinant of long-term morbidity and mortality in congenital heart disease. The right ventricle (RV) is genetically different from the left ventricle (LV), but it is unknown as to whether this has consequences for the cellular responses to abnormal loading conditions. In the LV, calcineurinactivation is a major determinant of pathological hypertrophy and an important target for therapeutic strategies. We studied the functional and molecular adaptation of the RV in mouse models of pressure and volume load, focusing on calcineurin-activation.
Multi-scale Structure-Function Relationships in Right Ventricular Failure Due to Pressure Overload
American journal of physiology. Heart and circulatory physiology, 2018
Right ventricular failure (RVF) is the major cause of death in pulmonary hypertension. Recent studies have characterized changes in RV structure in RVF, including hypertrophy, fibrosis and abnormalities in mitochondria. Few if any studies have explored the relationships between these multi-scale structural changes and functional changes in RVF. Pulmonary artery banding (PAB) was used to induce RVF due to pressure overload in male rats. Eight-weeks post-surgery, terminal invasive measurements demonstrated RVF with decreased ejection fraction (70±10% vs 45±15%, Sham vs. PAB, p<0.005) and cardiac output (126±40 mL/min vs. 67±32 mL/min, Sham vs. PAB, p<0.05). At the organ level, RV hypertrophy was directly correlated with increased contractility, which was insufficient to maintin ventricular-vascular coupling. At the tissue level, there was a 90% increase in fibrosis that had a direct correlation with diastolic dysfunction measured by reduced chamber compliance (R=0.43, p=0.008). ...
Regression of pressure overload-induced left ventricular hypertrophy in mice
AJP: Heart and Circulatory Physiology, 2005
As a prelude to investigating the mechanism of regression of pressure overload-induced left ventricular (LV) hypertrophy (LVH), we studied the time course for the development and subsequent regression of LVH as well as accompanying alterations in cardiac function, histology, and gene expression. Mice were subjected to aortic banding for 4 or 8 wk to establish LVH, and regression was initiated by release of aortic banding for 6 wk. Progressive increase in LV mass and gradual chamber dilatation and dysfunction occurred after aortic banding. LVH was also associated with myocyte enlargement, interstitial fibrosis, and enhanced expression of atrial natriuretic peptide, collagen I, collagen III, and matrix metalloproteinase-2 but suppressed expression of α-myosin heavy chain and sarcoplasmic reticulum Ca2+-ATPase. Aortic debanding completely or partially reversed LVH, chamber dilatation and dysfunction, myocyte size, interstitial fibrosis, and gene expression pattern, each with a distinct...
Journal of the American College of Cardiology, 2011
Objectives We sought to study whether patients with right ventricular failure (RVF) secondary to chronic thromboembolic pulmonary hypertension (CTEPH) have reduced left ventricular (LV) mass, and whether LV mass reduction is caused by atrophy. Background The LV in patients with CTEPH is underfilled (unloaded). LV unloading may cause atrophic remodeling that is associated with diastolic and systolic dysfunction. Methods We studied LV mass using cardiac magnetic resonance imaging (MRI) in 36 consecutive CTEPH patients (before/after pulmonary endarterectomy [PEA]) and 11 healthy volunteers selected to match age and sex of patients. We studied whether LV atrophy is present in monocrotaline (MCT)-injected rats with RVF or controls by measuring myocyte dimensions and performing in situ hybridization. Results At baseline, CTEPH patients with RVF had significantly lower LV free wall mass indexes than patients without RVF (35 Ϯ 6 g/m 2 vs. 44 Ϯ 7 g/m 2 , p ϭ 0.007) or volunteers (42 Ϯ 6 g/m 2 , p ϭ 0.006). After PEA, LV free wall mass index increased (from 38 Ϯ 6 g/m 2 to 44 Ϯ 9 g/m 2 , p ϭ 0.001), as right ventricular (RV) ejection fraction improved (from 31 Ϯ 8% to 56 Ϯ 12%, p Ͻ 0.001). Compared with controls, rats with RVF had reduced LV free wall mass and smaller LV free wall myocytes. Expression of atrial natriuretic peptide was higher, whereas that of ␣-myosin heavy chain and sarcoplasmic reticulum calcium ATPase-2 were lower in RVF than in controls, both in RV and LV. Conclusions RVF in patients with CTEPH is associated with reversible reduction in LV free wall mass. In a rat model of RVF, myocyte shrinkage due to atrophic remodeling contributed to reduction in LV free wall mass.
Heart failure in pressure overload hypertrophy
Journal of the American College of Cardiology, 2002
Heart failure in pressure overload hypertrophy: The relative roles of This information is current as of July 18, 2011 OBJECTIVES We sought to explore the relative contributions of ventricular remodeling and myocardial dysfunction to heart failure in pressure overload hypertrophy (POH). BACKGROUND The mechanism that underlies heart failure in POH is adverse left ventricular (LV) chamber remodeling or decreased myocardial function, or a combination of these.