Pre‐emptive heme oxygenase‐1 (HO‐1) gene delivery reduces mortality and preserves left ventricular function one‐year after acute myocardial infarction
Bibliographic record
Abstract
We reported previously that pre‐delivery of HO‐1 gene to the heart by adeno‐associated virus (AAV) markedly reduces ischemia and reperfusion (I/R) injury. However, the effect of pre‐emptive HO‐1 gene delivery on long‐term survival and LV structure and function has not been determined. We assessed the effect of HO‐1 gene delivery on long term survival, myocardial function and LV remodeling 1 year after myocardial infarction (MI) using echocardiography, pressure‐volume (PV) analysis and morphometric approaches. Two groups of Lewis rats were injected with 2 x 10 11 particles of AAV‐LacZ or AAV‐hHO‐1 in the apical region of the LV wall. Six weeks after gene transfer, animals were subjected to 30 min of ischemia by ligation of the left anterior descending artery followed by reperfusion. Echocardiographic measurements and analysis of LV function were obtained at 12 months after MI. One year after MI, mortality was markedly reduced in the HO‐1 animals. PV analysis showed enhanced LV developed pressure, elevated maximal dP/dt and lower end diastolic volume in the HO‐1 compared to the LacZ animals. Echocardiography showed a larger apical anterior‐to‐posterior wall ratio in HO‐1 animals. Morphometric analysis revealed a 62% decrease in myocardial scarring and fibrosis in the HO‐1 relative to the LacZ animals. We conclude that pre‐emptive HO‐1 gene delivery may be useful as a therapeutic strategy to reduce post MI LV remodeling and heart failure. Supported by CIHR grants to L.G. Melo and C.A. Ward
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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) | 0.001 | 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) | 0.001 | 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".