Role of oxidative stress in ischemia-reperfusion induced alterations in myofibrillar ATPase activities in the heart
Bibliographic record
Abstract
Although ischemia-reperfusion (IR) in the heart has been shown to produce myofibrillar remodeling and depress Ca2*-sensitivity of myofilaments, the mechanisms for these alterations are not clearly understood.Since the generation ofreactive species and oxidants is known to produce cardiac dysfunction in IR hearls, it is likely that changes in myofibrils occur as a consequence of oxidative stress due to IR in the myocardium.In this study, therefore, isolated rat hearts were subjected to global ischemia for 30 min followed by a 30 min period of reperfusion upon treatments with or without superoxide dismutase (SOD) plus catalase, an oxyradical scavenging mixture, or N-acetylcysteine (NAC), an antioxidant.Because IR is also known to produce intracellular Ca2*-overload and subsequent proteolysis, experiments were carried out upon treating the hearts with leupeptin, an inhibitor of Ct*-dependent protease.Alterations in cardiac function were monitored by measuring left ventricular developed pressure (LVDP), rate of pressure development (+dP/dt), rate of pressure decay (-dP/dÐ and left ventricular end diastolic pressure (LVEDP) whereas changes in myofibrils were determined by measuring myofibrillar ATPase activities and gene expression for c¿-and B-myosin heavy chain (MHC) as well as myosin light chain 1 (MLCi).IR was found to induce cardiac dysfunction as reflected by depressed LVDP, +dP/dt and -dP/dt as well as elevated LVEDP.These changes in cardiac ftinction were simulated upon perfusing the heart with xanthine (X) plus xanthine oxidase (XO), an oxyradical generating system, and HzOz, an oxidant.Deplession in myofibrillar Ca2*- stimulated ATPase activity in the IR heart was not associated with any changes in myofibrilla.Mg2* ATPase.Although myofibrillar Ca2*-stimulated ATPase activity was depressed, Mg2* ATPase activity was increased in hearts perfused with X and XO.The mRNA levels for c¿-MHC, P-MHC and MLC1 were decreased in IR hearls.Alterations in cardiac function, myofibrillar C**-ATPase as well as gene expression for cr-MHC, B- MHC and MCL1 in IR hearts were attenuated by pretreatments with SOD plus catalase mixture, NAC and leupeptin.These results suggest that oxidative stress and associated intracellular Ca2*-overload play an important role in myofibrillar remodeling in hearts due to IR injury.
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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 | 0.001 | 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".