Role of oxidative stress in ischemia–reperfusion-induced alterations in myofibrillar ATPase activities and gene expression in the heartThis article is one of a selection of papers from the NATO Advanced Research Workshop on Translational Knowledge for Heart Health (published in part 1 of a 2-part Special Issue).
Bibliographic record
Abstract
Ischemia-reperfusion (IR) in the heart has been shown to produce myofibrillar remodeling and depress Ca2+ sensitivity of myofilaments; however, the mechanisms for these alterations are not clearly understood. In view of the role of oxidative stress in cardiac dysfunction due to IR, isolated rat hearts were subjected to global ischemia for 30 min followed by a 30-minute period of reperfusion. IR was found to induce cardiac dysfunction, as reflected by depressed LVDP, +dP/dt, and -dP/dt, and elevated LVEDP, and to reduce myofibrillar Ca2+-stimulated ATPase activity. These changes were simulated by perfusing the hearts with a mixture of xanthine plus xanthine oxidase, which is known to generate oxyradicals. The alterations in cardiac function and myofibrillar Ca2+-stimulated ATPase in IR hearts were attenuated by pretreatment with antioxidants (superoxide dismutase plus catalase, and N-acetylcysteine) and leupeptin, an inhibitor of Ca2+-dependent protease. The levels of mRNA for myosin heavy chain isoforms (alpha-MHC and beta-MHC) and myosin light chain (MLC1) were depressed in IR hearts. These changes in gene expression due to IR were prevented upon perfusing the hearts with superoxide plus catalase, with N-acetylcysteine, or with leupeptin. The results suggest that oxidative stress due to IR injury and associated proteolysis play an important role in inducing changes in myofibrillar Ca2+-stimulated ATPase activity and gene expression in the heart.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".