The Right Ventricle

Archer, Stephen L.; Ryan, John; Rich, Stuart; Nathan, Sandeep; Tsai, Kevin; Patel, Amit R.; Yao, Fang; Piao, Lin

doi:10.1016/b978-0-12-381510-1.00038-7

Cited by 2 publications

(1 citation statement)

References 88 publications

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“…Regardless of the etiology, key histopathological features of pathological RV remodeling include the development of RV hypertrophy (RVH), ventricular dilatation and excessive extracellular matrix (ECM) deposition ( brosis) [7]. Whilst these changes are aimed at maintaining cardiac output and stabilizing the RV in the short-term, the long-term consequence is an inexorable progression to RVF and morbidity [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

The SGLT2i Dapagliflozin Reduces RV Hypertrophy Independent of Changes in RV Pressure Induced by Pulmonary Artery Banding

Connelly

Visram

et al. 2021

Preprint

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Background— Sodium glucose linked transporter 2 (SGLT2) inhibition not only reduces morbidity and mortality in patients with diagnosed heart failure but also prevents the development of heart failure hospitalization in those at risk. While studies to date have focused on the role of SGLT2 inhibition in left ventricular failure, whether this drug class might be similarly efficacious in the treatment and prevention of right heart failure has not been unexplored.Hypothesis: We hypothesized that SGLT2 inhibition would reduce the structural, functional and molecular responses to pressure overload of the right ventricle.Methods: Thirteen-week-old Fischer F344 rats underwent pulmonary artery banding (PAB) or sham surgery prior to being randomized to receive either the SGLT2 inhibitor: dapagliflozin (1.5mg/kg/day) or vehicle by oral gavage. After six weeks of treatment, animals underwent transthoracic echocardiography and invasive hemodynamic studies. Animals were then terminated, and their hearts harvested for structural and molecular analyses.Results: PAB induced features consistent with a compensatory response to increased right ventricular (RV) afterload with elevated mass, end systolic pressure, collagen content and alteration in calcium handling protein expression (all p<0.05 when compared to sham + vehicle). Dapagliflozin reduced RV mass, including both wet and dry weight as well as normalizing the protein expression of SERCA 2A, AMPkinase and LC3I/II ratio expression (all p<0.05).Significance: Dapagliflozin reduces the structural, functional, and molecular manifestations of right ventricular pressure overload. Whether amelioration of these early changes in the RV may ultimately lead to a reduction in RV failure remains to be determined.

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Section: Introductionmentioning

confidence: 99%

The SGLT2i Dapagliflozin Reduces RV Hypertrophy Independent of Changes in RV Pressure Induced by Pulmonary Artery Banding

Connelly

Visram

et al. 2021

Preprint

View full text Add to dashboard Cite

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The Right Ventricle in Pulmonary Arterial Hypertension

Ryan

Archer

2014

Circulation Research

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379

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The right ventricle (RV) is the major determinant of functional state and prognosis in pulmonary arterial hypertension (PAH). RV hypertrophy (RVH) triggered by pressure overload is initially compensatory but often leads to RV failure. Despite similar RV afterload and mass some patients develop adaptive RVH (concentric with retained RV function), whilst others develop maladaptive RVH, characterized by dilatation, fibrosis and RV failure. The differentiation of adaptive versus maladaptive RVH is imprecise but adaptive RVH is associated with better functional capacity and survival. At the molecular level, maladaptive RVH displays greater impairment of angiogenesis, adrenergic signaling and metabolism than adaptive RVH and these derangements often involve the left ventricle. Clinically, maladaptive RVH is characterized by increased NT-proBNP levels, troponin release, elevated catecholamine levels, RV dilatation and late gadolinium-enhancement on magnetic resonance imaging, increased 18fluorodeoxyglucose uptake on positron emission tomography and QTc prolongation on the electrocardiogram. In maladaptive RVH there is reduced inotrope responsiveness due to G-protein receptor kinase (GRK2)-mediated downregulation, desensitization and uncoupling of β-adrenoreceptors. RV ischemia may result from capillary rarefaction and/or decreased right coronary artery perfusion pressure. Maladaptive RVH shares metabolic abnormalities with cancer including aerobic glycolysis (resulting from a FOXO1-mediated transcriptional upregulation of pyruvate dehydrogenase kinase, PDK), and glutaminolysis (reflecting ischemia-induced cMyc activation). Augmentation of glucose oxidation is beneficial in experimental RVH and can be achieved by inhibition of PDK, fatty acid oxidation, or glutaminolysis. Therapeutic targets in RV failure include chamber-specific abnormalities of metabolism, angiogenesis, adrenergic signaling and phosphodiesterase-5 expression. The ability to restore RV function in experimental models challenges the dogma that RV failure is irreversible without regression of pulmonary vascular disease.

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The Right Ventricle

Cited by 2 publications

References 88 publications

The SGLT2i Dapagliflozin Reduces RV Hypertrophy Independent of Changes in RV Pressure Induced by Pulmonary Artery Banding

The SGLT2i Dapagliflozin Reduces RV Hypertrophy Independent of Changes in RV Pressure Induced by Pulmonary Artery Banding

The Right Ventricle in Pulmonary Arterial Hypertension

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