scholarly journals Importance of Cx43 for Right Ventricular Function

2021 ◽  
Vol 22 (3) ◽  
pp. 987
Author(s):  
Kerstin Boengler ◽  
Susanne Rohrbach ◽  
Norbert Weissmann ◽  
Rainer Schulz
Keyword(s):  
Pulmonary Hypertension ◽  
Left Ventricle ◽  
Right Ventricular ◽  
Connexin 43 ◽  
Therapeutic Strategies ◽  
Cx43 Expression ◽  
Developing Heart ◽  
And Function ◽  
Rv Function

In the heart, connexins form gap junctions, hemichannels, and are also present within mitochondria, with connexin 43 (Cx43) being the most prominent connexin in the ventricles. Whereas the role of Cx43 is well established for the healthy and diseased left ventricle, less is known about the importance of Cx43 for the development of right ventricular (RV) dysfunction. The present article focusses on the importance of Cx43 for the developing heart. Furthermore, we discuss the expression and localization of Cx43 in the diseased RV, i.e., in the tetralogy of Fallot and in pulmonary hypertension, in which the RV is affected, and RV hypertrophy and failure occur. We will also introduce other Cx molecules that are expressed in RV and surrounding tissues and have been reported to be involved in RV pathophysiology. Finally, we highlight therapeutic strategies aiming to improve RV function in pulmonary hypertension that are associated with alterations of Cx43 expression and function.

scholarly journals The Role of Four-Dimensional Automatic Right Ventricular Quantification Technology to Determine RV Function and Hemodynamics in Patients With Pulmonary Hypertension Compared With Right Heart Catheterization

2021 ◽  
Vol 8 ◽  
Author(s):  
Weichun Wu ◽  
Bingyang Liu ◽  
Min Huang ◽  
David H. Hsi ◽  
LiLi Niu ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Image Quality ◽  
Right Ventricular ◽  
Right Heart Catheterization ◽  
Heart Catheterization ◽  
Healthy Controls ◽  
Right Heart ◽  
Quality Image ◽  
Rv Function

Background: Four-dimensional automatic right ventricular quantification technology (4D auto-RVQ) is a new method that can simultaneously measure right ventricular (RV) structure and strain. The role of 4D auto-RVQ in determining RV function and hemodynamics is not clear. The role of 4D auto-RVQ in determining RV function and hemodynamics is not clear. We assessed the 4D auto-RVQ to measure right heart structure, function, and hemodynamics in patients with pulmonary hypertension (PHTN) correlated with right heart catheterization (RHC).Methods: We enrolled a prospective cohort of 103 patients with PHTN and 25 healthy controls between September 2017 and December 2018. All patients with PHTN underwent echocardiography and RHC. Patients were included if they underwent two-dimensional (2D) and 4D auto-RVQ echocardiographic sequences on the same day as RHC. We analyzed RV functional indices using 2D and 4D auto-RVQ analyses. We divided patients with PHTN into three groups according to echocardiographic image quality as follows: high (n = 24), average (n = 48), and poor (n = 4). Hemodynamic parameters were measured using RHC, including mean right atrial pressure, mean pulmonary arterial pressure, RV cardiac index (RV-CI), and pulmonary vascular resistance.Results: There were significant differences in most 2D and 4D auto-RVQ parameters between patients with PHTN and healthy controls. Interobserver variability showed significant agreement with 4D auto-RVQ for most measurements except for 4D end-diastolic volume. Indices measured by auto 4D-RVQ in the high-quality image group had a good correlation with RHC but not in the average- and poor-quality image group. Mid-RV diameter showed the best predictive power for the right RV-CI [area under the curve (AUC) 0.935; 95% confidence interval (CI), 0.714–0.997; p < 0.001]. RV end-systolic volume >121.50 mL had a 71.43% sensitivity and a 100% specificity to predict right RV-CI (AUC, 0.890; 95% CI, 0.654–0.986; p < 0.001).Conclusions: 4D auto-RVQ may be used to estimate RV function and some hemodynamic changes compared with RHC in PHTN patients with high image quality. Furthermore, a large sample of the study is needed to evaluate RV function by 4D auto-RVQ in PHTN patients with average image quality.

Abstract 13689: Right Ventricular Edema and Pericardial Effusion in Pulmonary Hypertension: Role of Lymphatics

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Kelley L Colvin ◽  
Ozus Lohani ◽  
Michael E Yeager
Keyword(s):  
Pulmonary Hypertension ◽  
Pericardial Effusion ◽  
Right Ventricular ◽  
Ventricular Remodeling ◽  
Myocardial Edema ◽  
Rat Models ◽  
Lymphatic Vasculature ◽  
Factor C ◽  
And Function ◽  
Rv Function

Introduction: Pulmonary hypertension (PH), regardless of etiology, is characterized by right ventricular remodeling and eventual failure. Pericardial effusion in the setting of PH is a serious and important clinical problem that portends a grim prognosis. Unfortunately, there are few mechanistic data available to explain its pathogenesis. Hypothesis: We hypothesized that the RV lymphatic vasculature and function would be decreased in PH associated with pericardial effusion. Methods: We examined human RV tissue from patients with PH and from rat models of PH with and without pericardial effusion and RV failure. We evaluated the extent of lymphatic vasculature, the presence of myocardial edema, and degree of pericardial effusion using invasive (immunoblot, immunohistology, RV wet/dry ratios) and non-invasive techniques (MRI, echocardiography, intravital imaging). To investigate whether neo-lymphangiogenesis affected RV function in PH, we treated rats with exogenous recombinant vascular endothelial growth factor C (VEGFC) before and during the development of PH. Results: We found decreased prox1+/podoplanin+ lymphatic vessels in RVs, but not left ventricles, from PH compared to either controls or to individuals with PH that lacked RV failure. The extent of lymphatic vasculature inversely correlated with the presence of myocardial edema, pericardial effusion, and positively correlated with cardiac output. In addition, the presence of increased interstitial fluid preceded development of RV fibrosis and was associated with increased numbers of tcf21+ RV fibroblasts. We found that administration of VEGFC induced a neo-lymphangiogenic response in RVs of rats, reduced myocardial edema, and promoted significant improvement in RV function. Conclusions: Decreased lymphatic vasculature and function likely contribute to myocardial edema and pericardial effusion in severe PH with RV failure. Augmentation of RV neo-lymphangiogenesis in rat models of PH greatly attenuated the edema, effusion, and fibrosis compared to vehicle controls. Collectively, these data raise the possibility that therapies to promote RV lymphangiogenesis and function may have important therapeutic benefit by reducing the high mortality of pericardial effusion in PH.

scholarly journals Emerging role of angiogenesis in adaptive and maladaptive right ventricular remodeling in pulmonary hypertension

2018 ◽  
Vol 314 (3) ◽  
pp. L443-L460 ◽  
Author(s):  
Andrea L. Frump ◽  
Sébastien Bonnet ◽  
Vinicio A. de Jesus Perez ◽  
Tim Lahm
Keyword(s):  
Pulmonary Hypertension ◽  
Prognostic Factor ◽  
Right Ventricular ◽  
Physiological Response ◽  
Ventricular Remodeling ◽  
Pressure Overload ◽  
Therapeutic Approaches ◽  
Right Ventricular Remodeling ◽  
Rv Function

Right ventricular (RV) function is the primary prognostic factor for both morbidity and mortality in pulmonary hypertension (PH). RV hypertrophy is initially an adaptive physiological response to increased overload; however, with persistent and/or progressive afterload increase, this response frequently transitions to more pathological maladaptive remodeling. The mechanisms and disease processes underlying this transition are mostly unknown. Angiogenesis has recently emerged as a major modifier of RV adaptation in the setting of pressure overload. A novel paradigm has emerged that suggests that angiogenesis and angiogenic signaling are required for RV adaptation to afterload increases and that impaired and/or insufficient angiogenesis is a major driver of RV decompensation. Here, we summarize our current understanding of the concepts of maladaptive and adaptive RV remodeling, discuss the current literature on angiogenesis in the adapted and failing RV, and identify potential therapeutic approaches targeting angiogenesis in RV failure.

CMR markers for early right ventricular dysfunction in precapillary pulmonary hypertension

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Vos ◽  
T Leiner ◽  
A.P.J Van Dijk ◽  
F.J Meijboom ◽  
G.T Sieswerda ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricle ◽  
Right Ventricular ◽  
Circumferential Strain ◽  
Peak Strain ◽  
Healthy Controls ◽  
Free Wall ◽  
Global Circumferential Strain ◽  
The Right ◽  
Rv Function

Abstract Introduction Precapillary pulmonary hypertension (pPH) causes right ventricular (RV) pressure overload inducing RV remodeling, often resulting in dysfunction and dilatation, heart failure, and ultimately death. The ability of the right ventricle to adequately adapt to increased pressure loading is key for patients' prognosis. RV ejection fraction (RVEF) by cardiac magnetic resonance (CMR) is related to outcome in pPH patients, but this global measurement is not ideal for detecting early changes in RV function. Strain analysis on CMR using feature tracking (FT) software provides a more detailed assessment, and might therefore detect early changes in RV function. Aim 1) To compare RV strain parameters in pPH patients and healthy controls, and 2) to compare strain parameters in a subgroup of pPH patients with preserved RVEF (pRVEF) and healthy controls. Methods In this prospective study, a CMR was performed in pPH patients and healthy controls. Using FT-software on standard cine images, the following RV strain parameters were analyzed: global, septal, and free wall longitudinal strain (GLS, sept-LS, free wall-LS), time to peak strain (TTP, as a % of the whole cardiac cycle), the fractional area change (FAC), global circumferential strain (GCS), global longitudinal and global circumferential strain rate (GLSR and GCSR, respectively). A pRVEF is defined as a RVEF >50%. To compare RV strain parameters in pPH patients to healthy controls, the Mann-Whitney U test was used. Results 33 pPH-patients (55 [45–63] yrs; 10 (30%) male) and 22 healthy controls (40 [36–48] yrs; 15 (68%) male) were included. All RV strain parameters were significantly reduced in pPH patients compared to healthy controls (see table), except for GCS and GCSR. Most importantly, in pPH patients with pRVEF (n=8) GLS (−26.6% [−22.6 to −27.3] vs. −28.1% [−26.2 to −30.6], p=0.04), sept-LS (−21.2% [−19.8 to −23.2] vs. −26.0% [−24.0 to −27.9], p=0.005), and FAC (39% [35–44] vs. 44% [42–47], p=0.02) were still significantly impaired compared to healthy controls. The RV TTP was significantly increased in pPH patients compared to healthy controls (47% [44–57] vs. 40% [33–43], p≤0.001). Conclusions Several CMR-FT strain parameters of the right ventricle are impaired in pPH patients when compared to healthy controls. Moreover, even in pPH patients with a preserved RVEF multiple RV strain parameters (GLS, sept-LS, and FAC) remained significantly impaired, and TTP significantly prolonged, in comparison to healthy controls. This suggests that RV strain parameters may be used as an early marker of RV dysfunction in pPH patients. Funding Acknowledgement Type of funding source: None

scholarly journals Endogenous Mammalian Cardiotonic Steroids—A New Cardiovascular Risk Factor?—A Mini-Review

Life ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 727
Author(s):  
Natalia Słabiak-Błaż ◽  
Grzegorz Piecha
Keyword(s):  
Adenosine Triphosphatase ◽  
Therapeutic Strategies ◽  
Structure And Function ◽  
Sodium Potassium ◽  
Sodium Homeostasis ◽  
Cardiovascular Tissue ◽  
Ancient Times ◽  
And Function ◽  
Regulation Of Blood Pressure

The role of endogenous mammalian cardiotonic steroids (CTS) in the physiology and pathophysiology of the cardiovascular system and the kidneys has interested researchers for more than 20 years. Cardiotonic steroids extracted from toads or plants, such as digitalis, have been used to treat heart disease since ancient times. CTS, also called endogenous digitalis-like factors, take part in the regulation of blood pressure and sodium homeostasis through their effects on the transport enzyme called sodium–potassium adenosine triphosphatase (Na/K-ATPase) in renal and cardiovascular tissue. In recent years, there has been increasing evidence showing deleterious effects of CTS on the structure and function of the heart, vasculature and kidneys. Understanding the role of CTS may be useful in the development of potential new therapeutic strategies.

Right ventricular morphology and function undergo complex changes after cardiac surgery

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P Wejner-Mik ◽  
J.D Kasprzak ◽  
E Szymczyk ◽  
K Wdowiak-Okrojek ◽  
A Ammer ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Right Ventricular ◽  
Artery Bypass ◽  
Public Institution ◽  
Transverse Diameter ◽  
Funding Source ◽  
Longitudinal Function ◽  
Echocardiographic Examination ◽  
And Function ◽  
Rv Function

Abstract Background An impairment of certain echocardiographic parameters of right ventricular (RV) function, such as tricuspid annular peak systolic excursion (TAPSE), is a known phenomenon in patients undergoing cardiac surgery. However, little is known about significance of these alterations with regard to other aspects of RV function. The aim of our study was to clarify this issue using parameters based on 3D echocardiography and speckle tracking technique. Methods The study population comprised 122 patients (92 men, mean age 65±11 years), referred for coronary artery bypass grafting and/or replacement of mitral or aortic valve. Patients undergoing tricuspid annuloplasty and with baseline suboptimal image quality were excluded from the study group. Transthoracic echocardiographic examination was performed on average 2±2 days prior to surgery (TTE1), and 7±4 days after surgery (TTE2), whereas follow-up TTE (TTE3) was performed on average 12±2months after the surgery. Parameters measured during these examinations included both standard and advanced indices of RV size and function (such as TAPSE, systolic velocity of tricuspid annulus (S'), fractional area change (FAC), RV ejection fraction (EF) and RV global longitudinal systolic strain (GLS), as well as a new parameter introduced by our team - RV shortening fraction (RV SF), calculated as the change in mid RV transverse diameter. Results Echocardiographic measurements were completed for TTE1, TTE2 and TTE3 in 95% of patients. We noticed a significant postoperative (TTE2) impairment of parameters of RV longitudinal function (TAPSE, S' and GLS; p<0,0001). However, neither RV size assessed by both 2D and 3D technique changed, nor the global RV function measured with the use of FAC and EF. Additionally during the postoperative period an increase in the value of a RV SF by 12.85% was observed. After 12 months (TTE3) we observed an improvement in the parameters of the longitudinal RV function. Conclusion Cardiac surgery results in an impairment of the longitudinal systolic RV function, with no influence on the global RV function. The preservation of global function results from increased RV SF. After 12 months, an improvement of the longitudinal function can be observed. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Grant Polish Cardiac Society

scholarly journals Delineating the molecular and histological events that govern right ventricular recovery using a novel mouse model of pulmonary artery de-banding

2019 ◽  
Vol 116 (10) ◽  
pp. 1700-1709 ◽  
Author(s):  
Mario Boehm ◽  
Xuefei Tian ◽  
Yuqiang Mao ◽  
Kenzo Ichimura ◽  
Melanie J Dufva ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Mouse Model ◽  
Pulmonary Artery ◽  
Right Ventricular ◽  
Exercise Capacity ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Sequence Of Events ◽  
Reverse Remodelling ◽  
Rv Function

Abstract Aims The temporal sequence of events underlying functional right ventricular (RV) recovery after improvement of pulmonary hypertension-associated pressure overload is unknown. We sought to establish a novel mouse model of gradual RV recovery from pressure overload and use it to delineate RV reverse-remodelling events. Methods and results Surgical pulmonary artery banding (PAB) around a 26-G needle induced RV dysfunction with increased RV pressures, reduced exercise capacity and caused liver congestion, hypertrophic, fibrotic, and vascular myocardial remodelling within 5 weeks of chronic RV pressure overload in mice. Gradual reduction of the afterload burden through PA band absorption (de-PAB)—after RV dysfunction and structural remodelling were established—initiated recovery of RV function (cardiac output and exercise capacity) along with rapid normalization in RV hypertrophy (RV/left ventricular + S and cardiomyocyte area) and RV pressures (right ventricular systolic pressure). RV fibrotic (collagen, elastic fibres, and vimentin+ fibroblasts) and vascular (capillary density) remodelling were equally reversible; however, reversal occurred at a later timepoint after de-PAB, when RV function was already completely restored. Microarray gene expression (ClariomS, Thermo Fisher Scientific, Waltham, MA, USA) along with gene ontology analyses in RV tissues revealed growth factors, immune modulators, and apoptosis mediators as major cellular components underlying functional RV recovery. Conclusion We established a novel gradual de-PAB mouse model and used it to demonstrate that established pulmonary hypertension-associated RV dysfunction is fully reversible. Mechanistically, we link functional RV improvement to hypertrophic normalization that precedes fibrotic and vascular reverse-remodelling events.

scholarly journals Right Ventricular Geometry and Function in Pulmonary Hypertension: Non-Invasive Evaluation

Diseases ◽  
2014 ◽  
Vol 2 (3) ◽  
pp. 274-295 ◽  
Author(s):  
Diletta Peluso ◽  
Francesco Tona ◽  
Denisa Muraru ◽  
Gabriella Romeo ◽  
Umberto Cucchini ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Non Invasive ◽  
Ventricular Geometry ◽  
And Function ◽  
Invasive Evaluation
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