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Abstract Wed020: Controlled Rigth Ventricular Pressure Overload Can Rescue Left Ventricular Dysfunction by Promoting Biventricular Adaptive Hypertrophy

2025· article· en· W4414962124 on OpenAlexaff
Matteo Ponzoni, Libo Zhang, Jennifer J. Zhang, Kaley Hogarth, John G. Coles, Jason T. Maynes

Bibliographic record

VenueCirculation Research · 2025
Typearticle
Languageen
FieldMedicine
TopicCardiovascular Function and Risk Factors
Canadian institutionsHospital for Sick Children
Fundersnot available
KeywordsPressure overloadMuscle hypertrophyHeart failureFibrosisVolume overloadEjection fractionVentricular remodelingMyocardial fibrosisPulmonary artery bandingHemodynamics

Abstract

fetched live from OpenAlex

Introduction: Pulmonary artery banding (PAB) has emerged as a potential strategy for left ventricular (LV) functional recovery in pediatric dilated cardiomyopathy (DCM), yet the underlying mechanisms remain unclear. This study establishes a small animal model to investigate the hemodynamic and molecular adaptations induced by PAB. Methods: Sprague-Dawley rats underwent left anterior descending (LAD) artery ligation, followed by PAB one-week post-injury (LAD+PAB, n=13). Control groups included sham (n=16), PAB-only (n=16), and LAD-only (n=15). Echocardiography was performed weekly, and histological and molecular analyses were conducted four weeks after surgery. Results: Compared to LAD-only rats, LAD+PAB animals exhibited positive LV remodeling with reduced LV end-diastolic volume (0.49±0.02 vs. 0.66±0.03 mL, p<0.001), improvement of LV ejection fraction (0.48±0.01 vs. 0.36±0.01, p<0.001), and normalization of mitral valve Doppler E/A (p<0.001). Histological analysis documented LV hypertrophy (p=0.005), increased LV cardiomyocyte diameter (p=0.001), and augmented neoangiogenesis (p=0.005) in LAD+PAB versus LAD-only hearts. Mechanistically, we observed reduced LV fibrosis (p=0.003) and fibroblast cellular senescence (p=0.02), and preserved phospholamban (PLN) phosphorylation in the LV of LAD+PAB versus LAD-only rats (pPLN/PLN, p=0.008). Discussion: PAB induced a biventricular compensated hypertrophic response, which contributed to LV functional recovery after injury by recruiting residual myocardial reserve, limiting fibrosis, and maintaining calcium handling pathways. This adaptive response suggests that controlled RV pressure overload can trigger beneficial ventricular-ventricular interactions, promoting myocardial remodeling. The reduction in LV fibrosis and cellular senescence observed in PAB-treated animals supports the role of PAB in mitigating progressive myocardial injury. Increased neoangiogenesis in both ventricles suggests that PAB-induced hypertrophy is accompanied by vascular adaptation, which may enhance metabolic efficiency. Preservation of PLN phosphorylation may constitute another potential mechanism by which PAB sustains LV contractility through improved calcium cycling. This study provides mechanistic insights into PAB as a therapeutic strategy for LV dysfunction and as a potential bridge-to-recovery therapy in acute pediatric heart failure.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.003
metaresearch head score (Gemma)0.002
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.093
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0030.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.002
Science and technology studies0.0010.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.023
GPT teacher head0.298
Teacher spread0.275 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2025
Admission routes1
Has abstractyes

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