Perivascular Excitation Tunnelling: a Novel and Preventable Cause of Cardiac Reperfusion Arrhythmias
Bibliographic record
Abstract
Abstract Background Reperfusion after myocardial ischaemia can lead to deadly arrhythmias, in part due to heterogeneities in electrophysiology (EP) across affected tissue. There is a need to understand the spatiotemporal dynamics of ischaemia-reperfusion arrhythmias (IRA), so that reperfusion strategies to prevent them can be found. Methods Langendorff-perfused rabbit isolated hearts were loaded with a voltage-sensitive dye. Epifluorescence imaging was used to track action potential propagation across the cardiac surface. The heart was simultaneously perfused ‘globally’ ( via the aorta) and ‘locally’ ( via cannulation of a single coronary artery) with an oxygenated physiological saline solution. Local perfusion was subsequently switched to and from solutions that mimic aspects of ischaemia (acidosis, hypoxia, hyperkalaemia, or a simulated ischaemia solution combining all three) or to no-flow. Subsequently, different reperfusion strategies were tested to reduce IRA re-entries. The most successful strategy for preventing re-entry was tested in Langendorff-perfused isolated pig hearts to assess the clinical relevance of the observed mechanism and treatment strategy. Results Upon sudden reperfusion of the cannulated coronary artery in rabbit hearts we observed a preferential recovery of electrical excitability along the vessel’s main branch (‘perivascular excitation tunnelling’, PVET). This resulted in re-entry in roughly half of the hearts. Hyperkalaemia and hypoxia, but not acidosis, were sufficient to lead to conduction block, PVET, and re-entry, with both PVET and re-entry more frequently observed after hyperkalaemia than hypoxia. PVET was also present in pigs and PVET-based re-entries were successfully prevented in rabbit and pig hearts by two-step reperfusion, first of the distal majority of the previously ischaemic region, and then of the remaining tissue from the proximal point. With this strategy, any PVET that developed in the distal tissue was blocked by the still inexcitable proximal tissue. Upon reperfusion of the proximal tissue, there was a reduced path length for PVET. As a consequence, the associated excitable gap was too short for re-entrant excitation. Conclusions We observed a novel arrhythmia mechanism upon coronary reperfusion (PVET), which suggests that preferential recovery of myocardial excitability along the reperfused vessel is an important mechanism underlying IRA formation. PVET-induced re-entry reliably occurred in both rabbit and pig hearts and could be prevented by two-step reperfusion. Graphical Abstract
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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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".