Myocardial infarction is one of the leading causes of death and incapacity worldwide. Reopening the culprit artery to restore oxygenation is essential to prevent irreversible myocardial damage, but can also lead to deleterious events including arrhythmias. In previous work with rabbits, we identified a new type of ischaemia-reperfusion arrhythmia occurring in the myocardium along the main branch of the reperfused vessel (“perivascular excitation tunnelling”, PVET) and showed that a 2-stage reperfusion method could prevent subsequent re-entrant arrhythmias.

Computational modelling of reperfusion using openCARP was performed. A simplified ventricular model was generated with an ischaemic area and a central channel representing the recovered myocardium around the reperfused vessel. With this model we could replicate PVET-induced arrhythmias and predicted that the size of the ischaemic area is a major determinant of arrhythmia likelihood. Prior work comparing small versus large rabbit hearts showed that larger hearts were indeed more likely to have re-entrant arrhythmias.¹

To assess possible clinical relevance, as well as to identify whether risk scales with heart size across species, we performed experiments in pig hearts. All investigations conformed to German animal welfare laws and were performed with ethical approval by the local Institutional Animal Care and Use Committee (Regierungspräsidium Freiburg, X-21/03B). Explanted pig hearts were Langendorff perfused with HEPES-buffered physiological solution and optical mapping of transmembrane voltage performed. A cannula was inserted into a coronary artery and local ischaemia was achieved by perfusion of a simulated ischaemic solution (high K⁺/low O₂ solution). Reperfusion was performed either by reperfusing the whole ischaemic area at once (1-stage), or in a sequential manner (2-stage, with the cannula initially pushed deep into the artery for the first reperfusion step, and subsequently returned to the original position).

We confirmed the presence of PVET in pig hearts, characterised by the preferential recovery of myocardial excitability along the main branch of the reperfused vessel. In hearts reperfused with the 1-stage method, PVET occurred in 11 of the 12 hearts, resulting in re‑entrant arrhythmias in 7 cases (N=12). The likelihood of PVET-driven re-entrant arrhythmias in the pig heart was no higher than in the rabbit heart, indicating that ischaemic size alone is not a sufficient parameter to predict arrhythmia. With the 2-stage protocol, PVET occurred in 4 of 6 hearts, but no re-entrant arrhythmias were observed. Thus, the two-stage protocol did not significantly alter PVET likelihood but did reduce the likelihood of re-entrant arrhythmias (p-value: 0.038; Fisher’s exact test). We are currently optimising the computational model to incorporate realistic vasculature geometries and species differences. Finally, we are testing a new catheter, developed together with OSYPKA AG, to assess the efficacy of a 2-zone reperfusion method in a preclinical setting, which involves two separately controlled flow beds, enabling simultaneous reperfusion with different solutions preventing a delay in tissue re-oxygenation. In the future, we hope to use imaging approaches and computational modelling for risk stratification to identify which patients would benefit from use of this catheter during percutaneous coronary intervention following myocardial infarction and thereby improve patient outcomes.