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May 6, 2025Frontiers in PhysiologyOpen Access

Acute ischaemia paradoxically accelerates RV activation via Purkinje-myocardial junctions, an effect abolished by rotigaptide.

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Why the study?

Although not all Purkinje-myocardial junctions are active at rest due to source-sink mismatch, whether gap junction uncoupling during acute ischaemia increases active junctions and activation complexity was unclear.

Comparison

Rotigaptide vs control during an ischaemia-reperfusion protocol

Design

Ex vivo optical mapping and computational modelling study

Key result

Acute ischaemia increased the number of active Purkinje-myocardial junctions, causing a paradoxical acceleration in right ventricular activation that was abolished by the gap junction enhancer rotigaptide.

Authors

RJRichard J. JabbourEBElham BehradfarMDMichael T Debney

Discussion

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Overview

Suggests gap junction modulation may alter ischaemic conduction in animals; leaves open clinical relevance for human ventricular arrhythmias.

Structured PICO

P
Population
12 Langendorff-perfused hearts from New Zealand white rabbits (~4 months old, 2.0-2.5 kg).
I
Intervention
Rotigaptide (50 nM) pretreatment prior to 40 min global ischaemia and 30 min reperfusion
C
Comparator
Control (ischaemia-reperfusion without rotigaptide)
O
Outcome
Percentage of right ventricle area activated within the first 5 mssurrogate

Main Result

Absolute Event Rate: 52% vs 62%

p-value: p=0.04

Acute ischaemia increases the number of active Purkinje-myocardial junctions leading to complex activation patterns, which can be mitigated by the gap junction enhancer rotigaptide.

Limitations

  • Inability to individually visualize Purkinje-myocardial junctions with current optical mapping techniques
  • Computational model did not account for myocardial heterogeneity
  • Did not include ischaemic effects on the Purkinje system in the computational model
  • Did not study changes associated with longer durations of ischaemia
  • Reduced depth of ischaemia due to not bubbling the physiological solution with nitrogen
  • Unable to individually visualize PMJs due to limitations of optical mapping techniques

Cite This Study

Jabbour et al. (2025) studied Acute ischaemia (n=12). Rotigaptide vs. Control (no rotigaptide) was evaluated on Percentage of right ventricle area activated within the first 5 ms (early ischaemia vs baseline) (p=0.04). Acute ischaemia increased the number of active Purkinje-myocardial junctions, causing a paradoxical acceleration in right ventricular activation that was abolished by the gap junction enhancer rotigaptide.

synapsesocial.com/papers/6a164116a2d9d2b88ec50d4ehttps://doi.org/10.3389/fphys.2025.1540400
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Gap junctional conductance in ventricular myocyte pairs isolated from postischemic rabbit myocardium.1992 · 39 citations
  2. 2Enhancement of Gap Junction Function During Acute Myocardial Infarction Modifies Healing and Reduces Late Ventricular Arrhythmia Susceptibility2016 · 47 citations
  3. 3Gap junction heterogeneity in reentrant ventricular tachycardia2006 · 5 citations
  4. 4Myocardial gap junction organization in ischemia and infarction1995 · 52 citations
  5. 5Reduced intercellular coupling leads to paradoxical propagation across the Purkinje-ventricular junction and aberrant myocardial activation2005 · 70 citations