scholarly journals An exploratory assessment of stretch-induced transmural myocardial fiber kinematics in right ventricular pressure overload

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Danial Sharifi Kia ◽  
Ronald Fortunato ◽  
Spandan Maiti ◽  
Marc A. Simon ◽  
Kang Kim
Keyword(s):  
Right Ventricular ◽  
Pressure Overload ◽  
Longitudinal Direction ◽  
Protective Role ◽  
Large Animal ◽  
High Frequency Ultrasound ◽  
Large Animal Models ◽  
Concentric Hypertrophy ◽  
Fiber Reorientation ◽  
Longitudinal Fiber

AbstractRight ventricular (RV) remodeling and longitudinal fiber reorientation in the setting of pulmonary hypertension (PH) affects ventricular structure and function, eventually leading to RV failure. Characterizing the kinematics of myocardial fibers helps better understanding the underlying mechanisms of fiber realignment in PH. In the current work, high-frequency ultrasound imaging and structurally-informed finite element (FE) models were employed for an exploratory evaluation of the stretch-induced kinematics of RV fibers. Image-based experimental evaluation of fiber kinematics in porcine myocardium revealed the capability of affine assumptions to effectively approximate myofiber realignment in the RV free wall. The developed imaging framework provides a noninvasive modality to quantify transmural RV myofiber kinematics in large animal models. FE modeling results demonstrated that chronic pressure overload, but not solely an acute rise in pressures, results in kinematic shift of RV fibers towards the longitudinal direction. Additionally, FE simulations suggest a potential protective role for concentric hypertrophy (increased wall thickness) against fiber reorientation, while eccentric hypertrophy (RV dilation) resulted in longitudinal fiber realignment. Our study improves the current understanding of the role of different remodeling events involved in transmural myofiber reorientation in PH. Future experimentations are warranted to test the model-generated hypotheses.

P4684Differential right ventricular adaptation patterns to chronic pressure overload

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
I Garcia Lunar ◽  
D Pereda ◽  
M Ascaso ◽  
P Jorda ◽  
C Galan ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Pressure Overload ◽  
Heart Catheterization ◽  
Sham Operation ◽  
Large Animal ◽  
Continuous Variables ◽  
Pulmonary Shunt ◽  
Large Animal Models ◽  
Underlying Mechanisms

Abstract Background Right ventricular (RV) dysfunction is the most important prognostic factor in chronic pulmonary hypertension (PH), but its underlying mechanisms are unknown. Clinical observation and prior experimental work suggest that RV pressure overload is not the only cause since the degree of RV adaptation varies with similar RV end-systolic pressures. Purpose Our aim was to characterize serial RV adaptation by cardiac magnetic resonance (CMR) in 3 different experimental large-animal models of increased afterload: a model of chronic postcapillary PH, a model of PH secondary to systemic-to-pulmonary shunt and a model of mechanical RV pressure overload (generated by pulmonary artery [PA] banding). Methods Four-week old piglets underwent pulmonary vein banding surgery to generate the chronic postcapillary PH model (n=20), aorto-pulmonary shunt (n=6), PA banding (n=7) or sham operation (n=7). They were followed up monthly with CMR and right heart catheterization (RHC). All procedures followed the “Principles of laboratory animal care”. Comparison of continuous variables among groups was performed with Mann-Whitney U test. Results Animals with either postcapillary PH or PH secondary to aorto-pulmonary shunt presented significant RV dilatation, hypertrophy and dysfunction that was maintained during follow-up (median RV end-systolic volume [RVESV]=32.6 ml/m2 for postcapillary PH and 32.6 ml/m2 for shunt vs. 16.1 ml/m2 in sham controls; median RV ejection fraction [RVEF]=61.5% for postcapillary PH and 60.5% for shunt vs. 69.6% in sham controls at the end of follow-up). Animals with PA banding also presented with significant RV dilatation and hypertrophy at the first month follow-up, but unlike all other groups, they developed reverse RV remodeling from the second month onwards and maintained normal RV volumes and RVEF values until the end of follow-up despite having severe RV hypertrophy (RV mass 22.6 g/m2 in PA banding vs. 16.1 g/m2 in controls at the 4th month follow-up; Figure). CMR parameters (median values). Conclusion In PH there is a maladaptive RV hypertrophy that is not present in a model of progressive RV pressure overload without alterations of the pulmonary circulation. Increased RV pressure overload alone does not fully explain PH-associated RV dysfunction. Further research is needed to clarify the underlying mechanisms of adaptive and maladaptive hypertrophy in PH. Acknowledgement/Funding The CNIC is supported by the Ministerio de Ciencia, Innovaciόn y Universidades and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence

Impaired NO-mediated vasodilation with increased superoxide but robust EDHF function in right ventricular arterial microvessels of pulmonary hypertensive rats

2007 ◽  
Vol 292 (6) ◽  
pp. H2737-H2744 ◽  
Author(s):  
Masahito Kajiya ◽  
Masanori Hirota ◽  
Yousuke Inai ◽  
Takahiko Kiyooka ◽  
Taro Morimoto ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Pressure Overload ◽  
Suppressive Effect ◽  
Protective Role ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
Small Arteries ◽  
Sprague Dawley Rats ◽  
Endothelial Nitric Oxide ◽  
Arteriolar Vasodilation

Pulmonary hypertension (PH) causes right ventricular (RV) hypertrophy and, according to the extent of pressure overload, eventual heart failure. We tested the hypothesis that the mechanical stress in PH-RV impairs the vasoreactivity of the RV coronary microvessels of different sizes with increased superoxide levels. Five-week-old male Sprague-Dawley rats were injected with monocrotaline ( n = 126) to induce PH or with saline as controls ( n = 114). After 3 wk, coronary arterioles (diameter = 30–100 μm) and small arteries (diameter = 100–200 μm) in the RV were visualized using intravital videomicroscopy. We evaluated ACh-induced vasodilation alone, in the presence of Nω-nitro-l-arginine methyl ester (l-NAME), in the presence of tetraethylammonium (TEA) or catalase with or without l-NAME, and in the presence of SOD. The degree of suppression in vasodilation by l-NAME and TEA was used as indexes of the contributions of endothelial nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF), respectively. In PH rats, ACh-induced vasodilation was significantly attenuated in both arterioles and small aretries, especially in arterioles. This decreased vasodilation was largely attributable to reduced NO-mediated vasoreactivity, whereas the EDHF-mediated vasodilation was relatively robust. The suppressive effect on arteriolar vasodilation by catalase was similar to TEA in both groups. Superoxide, as measured by lucigenin chemiluminescence, was significantly elevated in the RV tissues in PH. SOD significantly ameliorated the impairment of ACh-induced vasodilation in PH. Robust EDHF function will play a protective role in preserving coronary microvascular homeostasis in the event of NO dysfunction with increased superoxide levels.

Abstract 249: The Epigenetically Modified Pro-inflammatory Cardiac Fibroblast Drives Cardiomyocyte Dysfunction in Pulmonary Hypertension-induced Right Ventricular Pressure Overload

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Danielle R Bruns ◽  
Stephen F Thoemmes ◽  
Peter M Buttrick ◽  
Lori A Walker
Keyword(s):  
Dna Methylation ◽  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Cardiac Fibroblasts ◽  
Strong Predictor ◽  
Pressure Overload ◽  
Large Animal Model ◽  
Central Component ◽  
Large Animal ◽  
Dna Hypomethylation

Right ventricular (RV) dysfunction is a strong predictor of survival in a variety of clinical contexts including pulmonary hypertension (PH). Thus elucidating mechanisms that contribute to RV dysfunction is of great importance. Persistent inflammation, a central component of PH-induced RV dysfunction, is regulated in part by cardiac fibroblasts (Cfib). We hypothesized that persistent changes in the Cfib pro-inflammatory phenotype may be mediated through epigenetic processes such as DNA methylation and that secretion of inflammatory signals from activated Cfib drives cardiomyocyte dysfunction and contributes to myofibrillar disarray. Therefore the purpose of this investigation was to assess epigenetic changes to pro-inflammatory Cfib and the contribution of the Cfib secretome on myocyte function. We approached this question using a large animal model with significant resonance with human disease- the neonatal calf exposed to hypobaric hypoxia (HH). HH caused RV Cfib global DNA hypomethylation. RNA-seq identified 2115 genes significantly changed in HH including 193 transcriptional regulators and 21 genes involved in DNA methylation. Further, we identified 105 inflammatory genes with enrichment of IL-1β as a central node of inflammatory signaling. Mass spec profiling of conditioned media (CM) from Cfib isolated from the PH calf (PH-CM) also confirmed significant pro-inflammatory protein secretion. We then examined the effects of PH-CM on adult rat ventricular myocytes (ARVM) in culture. Brief exposure to PH-CM caused marked dedifferentiation of ARVM to a neonatal-like phenotype that exhibited spontaneous contractile behavior. This response was not seen in ARVM exposed to CM from Cfib from the normoxic RV. These data suggest the combination of pressure overload and hypoxia causes epigenetic reprogramming of pro-inflammatory Cfib, signaling a phenotypic transformation in a population of myocytes which likely contributes to RV dysfunction. Therapies that target this inflammatory process have the potential to prevent RV dysfunction.

Regional Left Ventricular Systolic Function in Relation to the Cavity Geometry in Patients With Chronic Right Ventricular Pressure Overload

Circulation ◽  
1995 ◽  
Vol 91 (9) ◽  
pp. 2359-2370 ◽  
Author(s):  
Sheng-Jing Dong ◽  
Adrian P. Crawley ◽  
John H. MacGregor ◽  
Yael Fisher Petrank ◽  
Dale W. Bergman ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Systolic Function ◽  
Pressure Overload ◽  
Left Ventricular Systolic Function ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Ventricular Systolic Function

Decreased Myocyte Tension Development and Calcium Responsiveness in Rat Right Ventricular Pressure Overload

Circulation ◽  
1997 ◽  
Vol 95 (9) ◽  
pp. 2312-2317 ◽  
Author(s):  
Dongsheng Fan ◽  
Thomas Wannenburg ◽  
Pieter P. de Tombe
Keyword(s):  
Right Ventricular ◽  
Pressure Overload ◽  
Ventricular Pressure ◽  
Tension Development

scholarly journals Molecular Mechanisms of Fetal Tendon Regeneration Versus Adult Fibrous Repair

2021 ◽  
Vol 22 (11) ◽  
pp. 5619
Author(s):  
Iris Ribitsch ◽  
Andrea Bileck ◽  
Alexander D. Aldoshin ◽  
Maciej M. Kańduła ◽  
Rupert L. Mayer ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Molecular Mechanisms ◽  
Unmet Need ◽  
Tendon Healing ◽  
Tendon Injury ◽  
Inflammatory Factors ◽  
Large Animal ◽  
Post Injury ◽  
Tendon Regeneration ◽  
Large Animal Models

Tendinopathies are painful, disabling conditions that afflict 25% of the adult human population. Filling an unmet need for realistic large-animal models, we here present an ovine model of tendon injury for the comparative study of adult scarring repair and fetal regeneration. Complete regeneration of the fetal tendon within 28 days is demonstrated, while adult tendon defects remained macroscopically and histologically evident five months post-injury. In addition to a comprehensive histological assessment, proteome analyses of secretomes were performed. Confirming histological data, a specific and pronounced inflammation accompanied by activation of neutrophils in adult tendon defects was observed, corroborated by the significant up-regulation of pro-inflammatory factors, neutrophil attracting chemokines, the release of potentially tissue-damaging antimicrobial and extracellular matrix-degrading enzymes, and a response to oxidative stress. In contrast, secreted proteins of injured fetal tendons included proteins initiating the resolution of inflammation or promoting functional extracellular matrix production. These results demonstrate the power and relevance of our novel ovine fetal tendon regeneration model, which thus promises to accelerate research in the field. First insights from the model already support our molecular understanding of successful fetal tendon healing processes and may guide improved therapeutic strategies.

scholarly journals One clot after another in COVID-19 patient: diagnostic utility of handheld echocardiogram

2021 ◽  
Vol 2021 (2) ◽  
Author(s):  
Gini Priyadharshini Jeyashanmugaraja ◽  
Evgeny Shloknik ◽  
Deborah Tosin Akanya ◽  
Kristin Stawiarski ◽  
Christopher Winterbottom ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Care Setting ◽  
Pressure Overload ◽  
Massive Pulmonary Embolism ◽  
Cardiac Ultrasound ◽  
Ventricular Dilation ◽  
Severe Respiratory Distress ◽  
Systemic Thrombolysis ◽  
Focused Cardiac Ultrasound ◽  
Right Ventricular Dilation

ABSTRACT A 63-year-old woman was admitted with severe respiratory distress requiring mechanical ventilation and shock requiring vasopressor support. She was found to have COVID-19 pneumonia. Focused cardiac ultrasound performed for evaluation of shock was significant for right ventricular dilation and dysfunction with signs of right ventricular pressure overload. Given worsening shock and hypoxemia systemic thrombolysis was administered for presumed massive pulmonary embolism with remarkable improvement of hemodynamics and respiratory failure. In next 24 h patient’s neurologic status deteriorated to the point of unresponsiveness. Emergent computed tomography showed multiple ischemic infarcts concerning for embolic etiology. Focused cardiac ultrasound with agitated saline showed large right to left shunt due to a patent foramen ovale. This was confirmed by transesophageal echocardiogram, 5 months later. This case highlights strengths of focused cardiac ultrasound in critical care setting and in patients with COVID-19 when access to other imaging modalities can be limited.

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