Role of iron chelation in hemorrhagic myocardial infarction: a quantitative CMR study
Bibliographic record
Abstract
It has been speculated that iron chelation may be beneficial in acute myocardial infarction (AMI) and that early treatment can limit ischemia-reperfusion injury and also reduce infarct size. However, the role of iron chelation in hemorrhagic myocardial infarction, where it would be most suited, has not yet been explored. Reperfusion hemorrhage results in accumulation of iron degradation products of hemoglobin that may be pro-inflammatory as free iron is toxic in nature. The purpose of the study was to investigate the interaction between iron chelating agent deferiprone (DFP) and hemorrhage in a porcine model of myocardial infarction and monitor remodeling by cardiovascular magnetic resonance (CMR). The study involved two groups of animals that were subjected to a 90 min balloon occlusion of the LAD followed by reperfusion - untreated (N=2) and DFP treated (N=2). DFP (supported by ApoPharma Inc., Toronto, ON) was administered (orally) a few hours before the procedure (pre-loading) and treatment was continued with a daily dose of 100 mg/kg. Imaging was performed on a 3T MRI scanner (MR 750, GE Healthcare) pre-AMI (healthy) and day 2-week 4 post-AMI. Edema was evaluated by T2 quantification using a T2-prepared spiral sequence and hemorrhage was identified by T2* determined using a multi-echo gradient-echo acquisition. Infarct assessment was performed by delayed hyperenhancement (DHE) using an IR-GRE sequence. Figure 1 demonstrates representative images from the two groups while Figure 2 shows the cumulative time course of the CMR measurements. In the DFP group, hemorrhage was observed only on day 2 and by week 1 it had completely resolved. This was in contrast to the untreated group where resolution of hemorrhage was delayed to week 4. With DFP, inflammation or edema was substantially reduced by week 4 with T2 values approaching control levels. In the untreated group, edema persisted up to week 4. Ejection fraction (EF) was depressed by week 4 in both groups. However, end-diastolic and end-systolic volumes were relatively unchanged in the DFP group while they increased significantly in the untreated group. Short axis images from a representative animals subjected to 90 min LAD occlusion without (top panel) and with (bottom panel) treatment of iron chelator deferiprone (DFP). In the DFP group, hemorrhage, as indicated by T2* image (red arrows) was observed only on day 2 but resolved by week 1, unlike the untreated group where hemorrhage persisted even at week 1. The iron neutralizing capacity of DFP is apparent from this example. In both groups, microvascular obstruction (MVO) was seen on day 2 that was partially resolved by week 1. Cumulative time course of T2 and T2* parameters post-AMI pooled across all animals (N=2) in the 90 min infarct - untreated (top panel) and treated with deferiprone (DFP, bottom panel); error bars show standard error and day 0 indicates control MRI scans in healthy animals. Infarct zone is shown in red; remote myocardium is shown in blue; hemorrhagic core is shown in black. Hemorrhage may be a source of iron toxicity and a mediator of inflammation, directly contributing to adverse remodeling in the setting of AMI. DFP was able to penetrate the infarct zone and was also effective in neutralizing hemorrhagic byproducts. Elimination of hemorrhage resulted in faster resolution of edema and normal ventricular volumes, representing a beneficial remodeling process. Iron chelation could potentially serve as an adjunctive therapy in hemorrhagic AMI.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".