Mechanisms by Which Adenosine Restores Conduction in Dormant Canine Pulmonary Veins
Bibliographic record
Abstract
BACKGROUND: Adenosine acutely reconnects pulmonary veins (PVs) after radiofrequency application, revealing "dormant conduction" and identifying PVs at risk of reconnection, but the underlying mechanisms are unknown. METHODS AND RESULTS: Canine PV and left-atrial (LA) action potentials were recorded with standard microelectrodes and ionic currents with whole-cell patch clamp before and after adenosine perfusion. PVs were isolated with radiofrequency current application in coronary-perfused LA-PV preparations. Adenosine abbreviated action potential duration similarly in PV and LA but significantly hyperpolarized resting potential (by 3.9+/-0.5%; P<0.05) and increased dV/dt(max) (by 34+/-10%) only in PV. Increased dV/dt(max) was not due to direct effects on I(Na), which was reduced similarly by adenosine in LA and PV but correlated with resting-potential hyperpolarization (r=0.80). Adenosine induced larger inward rectifier K(+)current (I(KAdo)) in PV (eg, -2.28+/-0.04 pA/pF; -100 mV) versus LA (-1.28+/-0.16 pA/pF). Radiofrequency ablation isolated PVs by depolarizing resting potential to voltages positive to -60 mV. Adenosine restored conduction in 5 dormant PVs, which had significantly more negative resting potentials (-57+/-6 mV) versus nondormant (-46+/-5 mV, n=6; P<0.001) before adenosine. Adenosine hyperpolarized both, but more negative resting-potential values after adenosine in dormant PVs (-66+/-6 mV versus -56+/-6 mV in nondormant; P<0.001) were sufficient to restore excitability. Adenosine effects on resting potential and conduction reversed on washout. Spontaneous recovery of conduction occurring in dormant PVs after 30 to 60 minutes was predicted by the adenosine response. CONCLUSIONS: Adenosine selectively hyperpolarizes canine PVs by increasing I(KAdo). PVs with dormant conduction show less radiofrequency-induced depolarization than nondormant veins, allowing adenosine-induced hyperpolarization to restore excitability by removing voltage-dependent I(Na) inactivation and explaining the restoration of conduction in dormant PVs.
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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 | 0.000 | 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 | 0.000 |
| 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".