Efficacy of Pretreatment With the Angiotensin II Type 1 Receptor Blocker UP269-6 and Losartan in the Dog: Effect on Hemodynamics and Ischemia-Reperfusion
Bibliographic record
Abstract
BACKGROUND: Whether pretreatment with the novel oral angiotensin II (AngII) type 1 receptor (AT(1)R) antagonist UP269-6 (UP) can produce more effective AT(1)R blockade than losartan (LN) for cardioprotection during ischemia-reperfusion (IR) in the dog has not been determined. METHODS AND MATERIALS: We compared the effect of UP (n = 5) and LN (n = 5) on serial in vivo hemodynamics, AngII pressor responses, and left ventricular (LV) volumes and function (echocardiograms) during escalation to optimal oral dosage over 7 days (day 0 to day 6), and acute IR (15 minutes ischemia, 30 minutes reperfusion) and ex vivo AT(1)R protein (Western immunoblots) with additional sham (n = 5) and IR (n = 5) controls on day 6. Compared with LN, UP produced greater vasodepression and decrease in diastolic volume during dose escalation and greater inhibition of the AngII pressor response over the range of escalating concentrations (0.05, 0.10, 0.25, and 0.50 microg/kg) on day 6. Acute IR after UP pretreatment resulted in less increase in LV filling pressure and LV diastolic and systolic volumes and greater ejection fraction, although UP and LN had similar effects on AT(1)R protein. CONCLUSION: Pretreatment with UP269-6 over 7 days produces more effective pharmacological AT(1)R blockade and cardioprotection after acute IR than LN in the dog.
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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 | 0.001 |
| 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 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".