Ischemia and reperfusion injury following cardioplegic arrest is attenuated by age and testosterone deficiency in male but not female mice
Bibliographic record
Abstract
BACKGROUND: Cardiovascular disease increases with age in both sexes. Treatment can require cardiac surgery, where the hearts are pre-treated with protective cardioplegic solution before ischemia and reperfusion (I/R). While endogenous estrogen is beneficial in I/R, whether testosterone is involved is uncertain and whether age modifies responses to I/R is unclear. We investigated sex- and age-specific differences in I/R injury in the hearts pre-treated with clinically relevant cardioplegic solution. METHODS: The hearts were isolated from young (6-9 months) and old (20-28 months) mice of both sexes and perfused (Langendorff) with Krebs-Henseleit buffer (15 min, 37 °C), followed by St. Thomas' two cardioplegia (6 min, 6-7 °C), global ischemia (90 min, 23-24 °C), and reperfusion (30 min, 37 °C). The hearts were perfused with triphenyltetrazolium chloride to quantify infarct area. Testosterone's role was investigated in gonadectomized (GDX, 6-9 months) male mice; serum testosterone and estradiol were measured with ELISA assays. RESULTS: Left ventricular developed pressure (LVDP) recovered to 67.3 ± 7.4% in the old compared to 21.8 ± 9.2% in the young male hearts (p < 0.05). Similar results were seen for rates of pressure development (+dP/dt) and decay (-dP/dt). Infarct areas were smaller in the old male hearts (16.6 ± 1.6%) than in the younger hearts (55.8 ± 1.2%, p < 0.05). By contrast, the hearts from young and old females exhibited a similar post-ischemic functional recovery and no age-dependent difference in infarcts. There was a sex difference in the young group, where ventricular function (LVDP, +dP/dt, -dP/dt) recovered better and infarcts were smaller in females than males. Estradiol levels were highest in young females. Testosterone was high in young males but low in females and old males, which suggested beneficial effects of low testosterone. Indeed, the hearts from GDX males exhibited much better recovery of LVDP in reperfusion than that from intact males (values were 64.4 ± 7.5 % vs. 21.8 ± 9.2%; p < 0.05). The GDX hearts also had smaller infarcts than the hearts from intact males (p < 0.05). CONCLUSIONS: Although age had no effect on susceptibility to I/R injury after cardioplegic arrest in females, it actually protected against injury in older males. Our findings indicate that low testosterone may be protective against I/R injury following cardioplegic arrest in older males.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".