Cardioprotection in The Mouse Heart: Acute Protective Effects of An Estrogen Receptor Agonist
Bibliographic record
Abstract
Background High calcium levels in ischemia promote contractile dysfunction and cell death in myocytes from aged or ovariectomized female mice. This suggests that low estrogen levels alter myocyte calcium homeostasis promoting ischemia and reperfusion (I/R) injury. Objective To determine whether the G‐protein coupled estrogen receptor (GPER) agonist, G1, enhances the benefits of a cardioplegic solution designed to protect hearts from ischemic damage. Methods Hearts were isolated from adult female and male mice (6–9 mos, n=28) for Langendorff perfusion experiments and then perfused with Krebs‐Henseleit buffer (37°C; 80 mmHg) for 15 min. Perfusion was interrupted and St. Thomas' 2 cardioplegic solution was delivered (6–9°C) either with G1 (500 nM), G1 (500 nM) + G15 (GPER antagonist; 1 μM) or with vehicle alone for 6 min. This was followed by 90 min global ischemia (23–24°C) and 30 min reperfusion (37°C). An enzyme‐linked immunosorbent assay (ELISA) was used to measure cardiac troponin‐I (cTnI) release from coronary effluent samples collected during reperfusion. Also, hearts were perfused with triphenyltetrazolium chloride (TTC) following reperfusion, which differentiated the infarcted (white) from viable (red) tissue. Results Post‐ischemic functional recovery in hearts perfused with cardioplegia + G1 (500 nM) was significantly better than cardioplegia alone in females. Left ventricular developed pressure (LVDP) recovered to 52.0 ± 11.5% for control vs. 75.6 ± 6.5% for G1 (p<0.05). Similar results were seen when the rates of pressure development (+dp/dt) and decay (−dp/dt) were assessed. Values for recovery of +dp/dt were 54.0 ± 12.1% vs. 77.6 ± 7.8% and for −dp/dt were 55.3 ± 12.2% vs. 81.0 ± 6.7% for control and G1, respectively. These effects of G1 were blocked by G15 (1 μM), where LVDP recovered to 57.0 ± 2%; +dp/dt and −dp/dt recovered to 60.4 ± 1.6% and 62.2 ± 3.6% respectively for G1 + G15 (p<0.05). cTnI release from female mouse hearts was slightly reduced in hearts treated with G1; values for cTnI were 9.0 ± 2.0 ng/ml and 6.5 ± 3.0 ng/ml for control and G1, respectively. Also, infarct sizes were smaller in the hearts treated with G1 (15.3 ± 3.6%) than the vehicle control (20.0 ± 3.5%), although this was not statistically significant. By contrast, no significant beneficial effects of G1 were observed in hearts from male mice (LVDP = 36.2 ± 5% for control vs. 49.0 ± 11.7% for G1). Conclusions These results demonstrate that addition of G1 enhances the cardioprotective properties of a standard cardioplegic solution and significantly improves functional recovery after ischemia in female mouse hearts. These results have the potential to improve outcomes during cardiac surgery. Support or Funding Information Canadian Institutes of Health research (CIHR), Nova Scotia Research and Innovation Graduate Scholarship (NSGS), Nova Scotia Health Research Foundation (NSHRF), Heart and Stroke Foundation (BrightRed Graduate Student Scholarship) This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 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 | 0.001 |
| 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".