Introduction. Myocardial infarction is one of the leading causes of death and incapacity in the world. The reopening of the culprit artery to restore tissue oxygenation is essential to prevent irreversible damage of the myocardium, but it can also lead to deleterious events including potentially lethal arrhythmias. In previous work with rabbits, we identified a new type of ischemia reperfusion arrhythmia occurring in the myocardium along the main branch of the reperfused vessel (“perivascular excitation tunnelling”, PVET) and showed that a 2-step reperfusion method could prevent them. In this work, we first investigate the presence of PVET in pig heart and the possibilities to prevent it using the 2-step reperfusion method. Next, test a new catheter, developed together with OSYPKA AG, to assess the efficacy of a 2-zone reperfusion method in a preclinical setting, which elevates advantages of 2-step reperfusion to a simultaneous reperfusion protocol with separately controlled flow beds, preventing a delay in tissue re-oxygenation.
Methods. Explanted porcine hearts were mounted on a Langendorff setup and perfused with physiological solution. For PVET investigation, a cannula was inserted into a coronary artery and local ischemia was achieved by perfusion of a simulated ischemic solution (high K+/low 02/low pH solution containing metabolic inhibitors). Reperfusion was either by reperfusing the whole infarcted area at once (1-step), or in a sequential manner (2-steps, with the cannula initially pushed deep into the artery for the first reperfusion step, and subsequently returned to the original position). For catheter testing, the proximal balloon was inflated, and simulated ischemic solution was perfused to the occluded flow bed. Reperfusion was either by deflating the proximal balloon (1-step), or involved inflating the distal balloon to create two separated flow beds to initiate the 2-zone reperfusion protocol. With this approach, ischemic areas are not sequentially but simultaneously reperfused using the two catheter’s lumens. The distal area is perfused with oxygenated saline and the proximal with oxygenated cardioplegic solution. Once the distal part regains electrical excitability, the distal balloon is deflated and proximal solution is switched to oxygenated saline. Optical mapping of membrane voltage was used throughout the procedures to monitor the electrical activity of the heart.
Results. We confirmed the presence of PVET in porcine heart, characterised by the preferential recovery of myocardial excitability along the reperfused main vessel’s branch. In hearts reperfused with the 1-step method, PVET occurred in 11 of the 12 hearts, resulting in re‑entrant arrhythmias in 7 cases (N=12). With the 2-step protocol, PVET occurred in 4 of 6 hearts, but no arrhythmias were observed. On-going tests with the newly developed catheter demonstrate feasibility to introduce and position it into the coronary arteries and use it to create well defined simultaneous flow beds.
Conclusion. PVET-based reperfusion arrhythmias are present, and preventable by 2-step reperfusion, in large animals. A newly developed catheter showed promising first results for its potential to replace the 2-step with a 2-zone perfusion method, which will be assessed ex vivo and in vivo.
