Abstract 4141614: Reducing the Risks of Complex Pediatric Cardiovascular Surgery using Glucagon-Like Peptide 1 Peptides
Bibliographic record
Abstract
Background: Children with critical congenital heart disease (CHD) often require complex open-heart surgery with long aortic cross-clamp times (XC). Despite refinement in cardioplegia, ventricular dysfunction due to inadequate myocardial protection remains a major clinical challenge. Glucagon-like peptide-1 (GLP-1) has proven cardioprotective properties. This study characterizes the mechanisms of injury of long XC and investigates cardioprotective properties of GLP-1(28-36), a naturally occurring fragment of GLP-1. Method&Results: A pediatric surgical model of cardiopulmonary bypass and long XC was developed in 4-5 wk-old Yorkshire pigs. Pigs were subjected to 90-min XC (modelling common CHD repair, e.g. Tetralogy of Fallot) or 180-min XC (modelling complex CHD repair, e.g. corrected transposition). After 90-min XC [n=8], analysis of cardiac function at baseline vs. 2-h post-bypass revealed reduced ejection fraction (55±6% vs. 28±4%; P<0.001) and global longitudinal strain (-11.5±1.5% vs. -6.8±1.2%; P<0.001). Levels of arterial lactate (0.6±0.1 vs. 3.9±0.8 mmol/L; P<0.001), myeloperoxidase (MPO: 39±4 vs. 124±28 ng/mL; P<0.001) and cardiac Troponin-I (cTnI: 0.01±0.01 vs. 4.8±0.6 ng/mL; P<0.001) indicate metabolic- and oxidative-stress and cardiomyocyte injury. Markedly reduced survival after 180- vs. 90-min XC (37.5% vs. 100% survival; n=8/group, P<0.05) was accompanied by more profound cardiac dysfunction, metabolic- and oxidative-stress, and cardiomyocyte injury in pigs surviving 180-min XC. Untargeted plasma metabolomics reveal XC time-dependent signatures ( Figure 1 ). Adding GLP-1(28-36) vs. control SCRAM(28-36) [30nM; n=8/group] to cardioplegia during 90-min XC caused longer time to first heart beat following XC (165±21 vs. 59±7 sec; P<0.001), with markedly reduced oxidative stress (MPO: 74±19 vs. 131±30 ng/mL; P<0.01) and cardiomyocyte injury (cTnI: 1.9±0.4 vs. 5.1±0.7 ng/mL; P<0.001). Conclusions: In a new model of long XC designed to simulate pediatric surgical repair of common and complex CHD, we demonstrate time-dependent cardiac dysfunction correlating with metabolic- and oxidative-stress and cardiomyocyte injury. Treatment with GLP-1(28-36) reduced injury and may mediate this by inducing hibernation.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".