1Universitäts-Herzzentrum Freiburg - Bad Krozingen Institut für Experimentelle Kardiovaskuläre Medizin Freiburg im Breisgau, Deutschland
Background: Reperfusion after an ischaemic period can lead to fatal arrhythmias. Typically, these arrhythmias are attributed to heterogeneities in the border zone between normally perfused myocardium and the reperfused myocardium. In previous work done in rabbits, we instead observed arrhythmias in the myocardium along the main branch of the reperfused coronary vessel (‘perivascular excitation tunnelling’, PVET) upon reperfusion.
Objective: To assess whether PVET occurs in a translationally-relevant model and to assess a two-step reperfusion method for preventing PVET-based arrhythmias.
Methods: Langendorff-perfused ex vivo pig hearts were used. The left marginal artery was separately cannulated and perfused to allow fine control of ischaemia and reperfusion. The hearts were loaded with a voltage-sensitive dye. Epifluorescence imaging was used to track action potential propagation during sinus rhythm, ischaemia, and reperfusion. Reperfusion was either one-step (sudden re-flow), or two-step, where the distal part of the ischaemic tissue was reperfused earlier than the proximal part.
Results: PVET occurred in 8 of the 9 pig hearts subjected to direct reperfusion, which lead to arrhythmias in 5 of the hearts. By comparison, the two-step reperfusion lead to PVET in 2 out of 4 hearts with no re-entry observed. The ‘distal-first’ two-step reperfusion of the blocked vessel did not give rise to re-entry, as the proximal part was still inexcitable – acting as a shield against break-through excitation. Upon subsequent reperfusion of the proximal tissue, any PVET-based re-entry that may develop in that tissue had a much reduced path length and the associated excitable gap was too short to allow re-entrant excitation. Subdividing reperfusion after acute ischaemic events into two spatially distinct domains meant that arrhythmogenic mechanisms were still present, but they were pathophysiologically silent.
Conclusion: PVET-based re-entry occurs in hearts with similar size, anatomy, and electrophysiology to humans, indicating it may be clinically relevant. We have developed a catheter that would allow controlled recovery of the ischaemic area in a two-zone reperfusion approach, where distal tissue is exposed to fully-physiological solution, while the proximal tissue is initially perfused with oxygenated but cardioplegic solution. This catheter will be tested in pig ex vivo and in vivo to identify if this constitutes an improved interventional tactic.