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Abstract 4142101: Preservation of Cardiac Function by Glucagon-Like Peptide-1 (28-36) through Metabolic Modulation and Coronary Vasodilation in a Juvenile Porcine Model of Donation after Circulatory Death

2024· article· en· W4404360037 on OpenAlexaff
Sachiko Kadowaki, M. Ahsan Siraj, Mimi Deng, Robert X. Lao, Jing Li, Anita Nagy, Brigitte Mueller, Marlee Parker, Junko Kobayashi, Mansoor Husain, Osami Honjo

Bibliographic record

VenueCirculation · 2024
Typearticle
Languageen
FieldMedicine
TopicPancreatic function and diabetes
Canadian institutionsUniversity of TorontoUniversity Health NetworkHospital for Sick Children
Fundersnot available
KeywordsMedicineCirculatory systemVasodilationInternal medicineCardiologyCardiac function curveHeart failure

Abstract

fetched live from OpenAlex

Purpose and Hypothesis: Despite the increasing number of donation after circulatory death (DCD) heart transplants over the last decade, there is no promising cardioprotective agent to improve DCD heart function in this clinical setting. There is some evidence that glucagon-like peptide (GLP)-1 (28-36), a metabolite of the insulinotropic GLP-1(7-36) incretin hormone, provides cytoprotection to the coronary vasculature without activating the GLP-1 receptor. This study aims to explore the potential benefits of GLP-1(28-36) on DCD hearts in juvenile pigs. Methods and Results: DCD heart procurement was performed on twelve Yorkshire juvenile pigs (9-12 kg) with a 15-min warm ischemic period, followed by reperfusion for 2 hours using ex-vivo heart perfusion (unloaded condition) with either GLP-1(28-36) or scrambled GLP-1(28-36) control (SCRAM) (each N=6, 6-nM), before switching to working mode (loaded condition). Between-group differences were analyzed using Wilcoxon rank-sum tests and linear mixed-effects models. Over the reperfusion period, venous lactate levels trended down in the GLP-1(28-36) group, compared to SCRAM (3.0±1.1 vs. 4.4±0.5, mmol/L at 120min, p=0.01; Figure 1A ), despite no significant difference seen in plasma cardiac troponin I levels in working mode (GLP-1[28-36] vs. SCRAM, 61±20 vs. 83±18, ng/mL, p=0.08). Coronary vascular resistance was lower in the GLP-1(28-36) group vs. SCRAM (0.48±0.11 vs. 0.93±0.51 mmHg*min/mL/100g at 30min, p<0.01; Figure 1B ). During working mode, GLP-1(28-36)-treated hearts showed better diastolic function (dp/dt min: -3357±784 vs. -2372±471 mmHg/sec, p=0.03), with comparable systolic function (p=0.13). Higher levels of cardiac activated endothelial nitric oxide synthase (0.23±0.05 vs. 0.14±0.02, p<0.01) and plasma cyclic guanosine monophosphate (45±22 vs. 23±11, pmol/mL, p=0.03) were observed with GLP-1(28-36) treatment. Conclusion: GLP-1(28-36) preserves diastolic function of DCD hearts during ex-vivo heart perfusion by reducing anaerobic metabolism and maintaining coronary endothelial function.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.010

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0030.000

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 head0.025
GPT teacher head0.252
Teacher spread0.227 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
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
Published2024
Admission routes1
Has abstractyes

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