Comparison of the In Vivo Hemodynamic Effects of the Antiarrhythmic Agents Vernakalant and Flecainide in a Rat Hindlimb Perfusion Model
Bibliographic record
Abstract
A series of in vivo experiments were conducted to compare the hemodynamic actions of vernakalant (a novel, relatively atrial selective, antiarrhythmic drug) to flecainide after infusion into the peripheral vasculature. Anesthetized rats were surgically prepared to have an extracorporeal perfusion circuit whereby blood in the abdominal aorta (distal to the renal arteries) was diverted to a constant flow pump and returned to the abdominal aorta at the same level allowing measurement of hindlimb vascular resistance. The effects of cumulative, ascending doses of intravenous vernakalant and flecainide on vascular resistance, after arterial pressures, and heart rate were measured. Blood samples were drawn following each dose to determine drug plasma concentrations. Vernakalant had no significant vasomotor effects on peripheral or systemic vasculature. In contrast, flecainide decreased peripheral vascular resistance (15% at 0.8 μg/mL) and systemic pressures (32% mean arterial pressure at 0.8 μg/mL) in a dose-dependent manner. At therapeutic plasma concentrations, vernakalant (1 μg/mL) had little effect on heart rate (-24 beats/min) or QRS intervals (+3.4 msec), whereas flecainide (0.8 μg/mL) significantly decreased heart rate (55 beats/min) and increased QRS intervals (9.9 msec). In conclusion, vernakalant did not have negative hemodynamic effects at therapeutic plasma concentrations in a rat hindlimb perfusion model.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| 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) | 0.000 | 0.000 |
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 teacher head, 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".