Abstract 12366: Intracoronary Delivery of E06 Antibody Directed to Oxidized Phospholipids Decreases Infarct Size in a Porcine Model of Ischemia/Reperfusion Injury
Bibliographic record
Abstract
Introduction: Myocardial ischemia/reperfusion injury (IRI) results in additional myocardial cell loss post reperfusion. Oxidized phosphocholine(PC)-containing phospholipids (OxPL) have been shown to result in cardiomyocyte cell death during IRI. E06 is a natural murine monoclonal IgM antibody which binds to the PC headgroup of OxPL. Transgenic mice expressing a single-chain Fv E06 fragment have recently been shown to have smaller infarct sizes post myocardial IRI. The objective of this study was to determine if directly infused E06 IgM reduced IRI in a porcine model of reperfusion injury that more closely reflects human physiology. Methods: Male pigs, 45 to 50 kg, were randomized equally to IRI in two groups: 1) control with saline coronary infusion (n=7). 2) IgM E06 coronary infusion over 1 hour (n=7). The left anterior descending (LAD) artery was occluded distal to the second diagonal branch for 60 minutes using an angioplasty balloon. Following balloon deflation, saline or IgM E06 was infused over 60 min through a microcatheter. Following 120 min of total reperfusion, the area at risk (AAR) and infarct size (IS) were determined by triphenyltetrazolium chloride staining technique (TTC), and myocardial salvage index determined. Results: All animals survived post reperfusion and no differences were present in hemodynamics at the baseline and 2 h post reperfusion between groups. A 51.3% reduction in infarct size was noted in animals receiving intracoronary E06 compared to controls (IS/AAR 21.7% ± 3.4 vs 42.3% ± 3.7 p<0.0005). IS/LV size (7.7 ± 3.2 vs 11.9 ± 1.2 p<0.004) and myocardial salvage index (82.6% vs 57.6% in controls) were significantly improved in animals receiving E06 compared to controls. Conclusion: Intracoronary delivery of E06 antibody at the time of reperfusion leads to a significant reduction in infarct size, suggesting that generation of OxPL during reperfusion leads to cardiomyocyte cell death. Translation of this approach using humanized anti-OxPL antibodies may allow a novel approach to treat myocardial IRI in humans.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.007 | 0.001 |
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".