Nitroglycerin reduces myocardial oxygen consumption during exercise despite vascular tolerance
Bibliographic record
Abstract
The long-term benefits of nitroglycerin (NTG) therapy are limited by the development of vascular tolerance and endothelial dysfunction in conductance coronary arteries. We have determined whether nitrate tolerance extends to NTG effects on myocardial O2 consumption (MV(O2)) and the ability of endogenous nitric oxide (NO) to modulate MV(O2) during exercise. In chronically instrumented dogs (n = 8), hemodynamic and MV(O2) responses to treadmill exercise were measured before, during tolerance (3 and 7 days of NTG delivery), and 7 days after NTG withdrawal. Acute NTG delivery caused a parallel downward shift of the MV(O2)-triple product (TP) relations and reversed the disproportionate increases in MV(O2) caused by the blockade of NO formation. After 7 days of continuous transdermal NTG delivery, vascular tolerance was displayed as a >75% reduction of coronary blood flow (CBF) responses to NTG boluses. Despite vascular nitrate tolerance, MV(O2)-TP relations were shifted downward compared with pre-NTG exercise. Seven days after NTG withdrawal, vascular responses to boluses of NTG had recovered from tolerance, and MV(O2)-TP relations during exercise were back to pre-NTG level. At that time, blockade of NO formation failed to alter MV(O2)-TP relations. Thus NTG caused a sustained reduction of cardiac MV(O2), independent of metabolic demand during exercise, despite tolerance of the coronary microcirculation. NTG-induced vascular tolerance and MV(O2) reductions were reversible by NTG withdrawal, but endogenous NO-dependent modulation of O2 consumption was severely impaired.
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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) | 0.000 | 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) | 0.000 | 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 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".