Abstract 8681: The Cardioprotective Role of Renin-Angiotensin System Antagonism in the Prevention of Doxorubicin and Trastuzumab Mediated Cardiac Dysfunction
Bibliographic record
Abstract
Background: In breast cancer patients, the administration of chemotherapeutic based agents, in particular Doxorubicin (Dox), is associated with an increased risk of cardiotoxicity. The introduction of novel monoclonal antibodies in breast cancer therapy, specifically Trastuzumab (Trz), further compounds this issue of drug induced cardiac dysfunction. Little is known about the use of renin-angiotensin system (RAS) antagonists in the prevention of Dox and Trz mediated cardiac dysfunction. Objective: To evaluate the cardioprotective effects of RAS antagonism in the prevention of Dox and Trz mediated cardiomyopathy in a chronic murine model. Methods: A total of 120 C57Bl/6 mice were randomized to three arms: (A) Trz; (B) Dox; or (C) Dox+Trz. The mice in each arm were further randomized to receive prophylactic treatment daily in their drinking water with either placebo, direct renin inhibitor (DRI), angiotensin converting enzyme inhibitor (ACEI), or angiotensin receptor blocker (ARB). Serial murine echocardiography was performed weekly for 13 weeks, after which the hearts were removed for histopathologic analyses. Results: In arm A (Trz), there was no evidence of cardiotoxicity at week 13. In arms B (Dox) and C (Dox+Trz), prophylactic treatment with either RAS antagonist was partially cardioprotective. In arm C (Dox+Trz), mice prophylactic treated with either placebo, DRI, ACEI or ARB demonstrated a decrease in fractional shortening from 51±2% at baseline to 26±2%, 40±2%, 32±2% and 34±2% (p<0.05), at week 13, respectively. Survival analyses of each arm corroborated the echocardiographic findings (Figure 1). There was a decrease in histologic evidence of cardiac damage due to Dox+Trz pretreated with either RAS antagonist. Conclusion: Prophylactic administration of RAS antagonists is partially cardioprotective in a chronic murine model of chemotherapy induced cardiac dysfunction. Figure 1:
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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) | 0.001 | 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 | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 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".