A58 UTILIZATION OF HYPOXIA-TOLERANT ORGANISMS AS A MODEL IN THE STUDY OF ISCHEMIC-REPERFUSION INJURY IN TRANSPLANT HEPATOLOGY
Bibliographic record
Abstract
Abstract Background Ischemic-reperfusion injury (IRI) is a barrier to successful liver transplantation. This complex process is initiated by an episode of hypoxia and decreased adenosine triphosphate (ATP) production. Mammalian hepatocytes are susceptible to prolonged hypoxia and may experience irreversible damage with ATP depletion. Yet, facultative anaerobes have developed physiological hepatoprotective strategies to tolerate hypoxic stress. The painted turtle (Chrysemys picta belli) and the common goldfish (Carassius auratus) are able to survive under severe hypoxia for weeks to months. Aims Introducing hypoxia-tolerant organisms as a suitable animal model for studying IRI in transplant hepatology. Methods A comprehensive search of PubMed, OVID, CINAHL, and Cochrane databases up to May 2023 was conducted to identify all studies reporting experimental evidence and hepatoprotective pathways in hypoxia-tolerant organisms (HTOs). Each article was qualitatively assessed. The primary focus was on cell death, intracellular ion gradient, mitochondrial function, and reactive oxygen species (ROS) with hypoxia and IRI. Results HTOs have increased glycogen storage with a greater ATP yield from anaerobic metabolism (glycolysis). Approximately 15-30% of liver mass in HTOs is composed of glycogen which is massive compared to 5-6% in mammals. Turtle isolated hepatocytes can tolerate 10 hours of anoxia by reducing cellular metabolic demand by 90% through decreased protein synthesis and ion channel activity. Goldfish hepatocytes can tolerate 6 hours of anoxia via similar strategies. In mammals, mitochondria undergo depolarization, Ca2+ efflux, cellular swelling, and apoptosis with anoxia. Yet, a depolarized mitochondrial membrane potential is regulated to provide cellular protection in HTOs. The ability to preserve mitochondrial function and electrochemical gradients with oxygen lack is an important contributor to cellular survival. Even in mammalian hepatocytes, if the mitochondrial integrity is maintained, cells are better able to tolerate ischemic insults. Finally, formation of radicals with reperfusion leads to hepatocyte apoptosis and necrosis in the mammalian model. Meanwhile, regulated ROS levels in turtles and goldfish cells, prevent cell death and IRI. Conclusions IRI is of significant interest in transplant hepatology. Although extremely valuable, the traditional mammalian models are vulnerable to hypoxia. Meanwhile, HTOs have undergone years of adaptation with thousands of genes dedicated to hypoxia tolerance. Utilizing these organisms can provide a broader understanding of IRI and avoid irreversible tissue damage in transplant hepatology. Funding Agencies CIHR
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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 | 0.005 | 0.015 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.005 | 0.004 |
| Bibliometrics | 0.019 | 0.018 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.003 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.008 | 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".