Effects of First and Second Generation Calcium Channel Blockers on Diastolic Function of the Failing Hamster Heart: Relationship with Coronary Flow Changes
Bibliographic record
Abstract
Calcium channel blockers (CCBs) have variable efficacy in the treatment of heart failure. We hypothesized that modulation of left ventricular diastolic pressure (LVDP) may play a role in the variable efficacy of CCBs in this condition. Isolated perfused hearts from 200- to 250-day-old UM-X7.1 cardiomyopathic hamsters (failing hearts) and age-matched Syrian hamsters (normal hearts) were studied. After recording of heart rate, coronary flow (CF), LVDP and left ventricular systolic pressure (LVSP), hearts were exposed either to verapamil or diltiazem (1 nM-10 microM), mibefradil (1 nM-1 microM) or clentiazem (1 nM-10 microM). Mechanical increase in CF (+2 to +10 ml/min) was carried out using a roller pump. Mechanically-augmented flow led to an increase in coronary perfusion pressure (+40 to +90 mm Hg), LVSP (+5 to +40 mm Hg) and LVDP (+5 to +25 mm Hg). CCBs-induced increment of coronary flow led to a difference in their cardiac response. In normal hearts, the negative inotropic response was more important with diltiazem and verapamil. Failing hearts did not demonstrate increased inotropic sensitivity to first-generation CCBs. On the contrary, at clinically relevant concentrations, verapamil resulted in the most pronounced impairment of LVDP followed by diltiazem while mibefradil and clentiazem, at clinically relevant concentrations, preserved LVDP. Such findings provide an additional explanation for the variable efficacy of CCBs in heart failure.
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 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 | 0.000 | 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 | 0.000 |
| 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".