Clin Res Cardiol (2022). https://doi.org/10.1007/s00392-022-02002-5

Perivascular Excitation Tunnelling in Ischaemia-Reperfusion is Enhanced with Increased Heart Size

E. Chleilat1, T. Puig Walz1, P. Kohl1, C. Zgierski-Johnston1, for the study group: UHZ-BK

1Institut für Experimentelle Kardiovaskuläre Medizin, Universitäts-Herzzentrum Freiburg - Bad Krozingen GmbH, Freiburg im Breisgau;

Introduction: Reperfusion after myocardial ischaemia can lead to fatal arrhythmias, in part due to heterogeneities in electrophysiology across affected tissue. We have previously reported a novel mechanism of reperfusion arrhythmias, where preferential recovery of electrical excitability of myocardium along the main branch of the perfused coronary vessel leads to re-entrant excitation (PeriVascular Excitation Tunnelling, PVET).1 The aim of this work was to elucidate the risk factors for PVET-based arrhythmias to occur. Methods: Experiments involved optical mapping for high-resolution spatio-temporal visualisation of transmembrane potentials in Langendorff-perfused ex vivo hearts from two to four-month old rabbits. In addition to perfusion of the coronary vasculature via the aortic root (Langendorff mode), a branch of the left coronary artery was cannulated and perfused independently from the remainder of the heart. Initially, all tissue was perfused with identical oxygenated HEPES-buffered physiological solution. In the separately perfused artery, flow was either temporarily stopped or this was switched to and from solutions mimicking different aspects of ischaemia – hypoxia, hyperkalaemia, acidosis, or a combination of the three (simulated ischaemic solution). Results: There was no difference in incidences of excitation block, PVET, or re-entry between simulated ischaemic solution and no-flow ischaemia. When examining three different aspects of ischaemia independently, acidosis alone was observed to not lead to block, PVET, or re-entry. Interestingly, while hypoxia was more likely to cause block than hyperkalemia, it was less likely to be followed by PVET or re-entry upon reperfusion. When comparing larger and smaller hearts, the incidence of PVET-induced arrhythmias scaled with heart size. Conclusions: PVET upon post-ischaemic reperfusion appears to be driven by hyperkalaemia, with less influence of hypoxia and no discernible effect of acidosis. Larger hearts were more likely to have PVET-based arrhythmias, indicating that this mechanism may be underrepresented in small experimental animals, and perhaps more likely in the clinical setting. We are currently studying PVET in pig hearts, to assess how this novel arrhythmia mechanism scales to species and with hearts closer to human size. Reference: 1 Chleilat E, Puig Walz T, Seemann G, Kohl P and Zgierski-Johnston CM. Perivascular excitation tunnelling in ischaemia-reperfusion. 2020 German Cardiac Society 86th Annual Meeting. Clin Res Cardiol 2020/109 (Suppl 1):P880. doi: 10.1007/s00392-020-01621-0

https://dgk.org/kongress_programme/jt2022/aP1971.html