Preconditioning for cardioprotection against ischemia reperfusion injury: the roles of nitric oxide, reactive oxygen species, heat shock proteins, reactive hyperemia and antioxidants--a mini review.
Bibliographic record
Abstract
BACKGROUND: In recent years, extensive studies have expanded the knowledge of the role of preconditioning (PC) for cardiac protection against ischemia reperfusion (I/R) injury. These studies are reviewed, and their relevance to the early and late phases of cardiac protection is discussed. CONCLUSIONS: First, there is strong evidence that the L-arginine-nitric oxide pathway plays a major role in PC. Second, early and late phase protection are probably distinct phenomena with similar effects induced by different mechanisms. Third, nitric oxide appears to be causally involved in both mechanisms. Fourth, nitric oxide produced by endothelial nitric oxide synthase (eNOS) in the early seconds of ischemia induces reactive hyperemia. It is proposed that reactive hyperemia provides the short-lived protection of early phase PC. It is unlikely that heat shock protein 72 (HSP72) or antioxidants have a role in early phase protection--both have a time lag of 12 to 24 h after PC before gene expression occurs. Fifth, late phase PC appears to depend on HSP72 gene expression mediated by the L-arginine-nitric-oxide pathway; during late phase PC, the inducible nitric oxide synthase (iNOS) content is increased while the eNOS content is unchanged. There is good evidence for an obligatory role of iNOS in cardiac protection afforded by the late phase of I/R protection in vivo. Sixth, the results of studies on the role of endogenous antioxidants in late phase protection are contradictory and further study is required. Seventh, studies on the signalling and transduction processes associated with preconditioning provide important information that may be helpful in the development of drugs protective against I/R injury. Finally, until such drugs are developed, PC by heat shock may be an effective alternative. A recent study in a human subject reported that HSP72 is upregulated by induction of hyperthermia within a range of moderate fever levels--oral temperatures between 38.6 degrees C and 39.5 degrees C. If this is confirmed, it seems plausible that inducing hyperthermia 24 h before major cardiac surgery may be an effective therapeutic strategy for protection against I/R.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".