A New Ex-Vivo Working Heart Model without Ischemia-Reperfusion Damage

Background: Rhythm and conductance disturbances may lead to heart failure. For better understanding of these circumstances electrophysiological studies are often performed using conventional Langendorff circulations or in-vivo studies. Limitations of in-vivo models include the difficulty accessing the left atrium between the pulmonary veins. In the well-established technique of Langendorff perfusion damages to the myocardium may arise from inevitable ischemia-reperfusion injury. Ischemia-reperfusion injury affects the electrophysiological properties of the myocardium, thus presenting an obstacle in conventional Langendorff perfusion. Therefore, we developed an ex-vivo working pig heart model without ischemia-reperfusion injury circumventing these limitations.

Methods: After full heparinization a median sternotomy was performed. The heart was exposed and the aortic root cannulated. Vent catheters were placed in the left ventricle via left atrial appendage and in the right ventricle via right atrial appendage. Extracorporeal circulation was started after the aorta and caval veins were clamped resulting in a coronary perfusion at 37°.

Results: The heart was stabilized achieving physiologic hemodynamic and metabolic parameters confirmed by repeated blood gas analyses. The beating heart-lung block was explanted and placed on a net to be able to reach all regions of the heart, especially the posterior left atrium between the pulmonary veins. Ablation and mapping catheters were inserted into the coronary sinus and a custom-made multi-electrode mapping system was placed around the heart. The heart has been successfully explanted without arresting the heart with subsequent ischemia. Metabolic, electrophysiologic and histologic parameters did not significantly changed after 1, 2, and 4 hours after ex-vivo perfusion compared with baseline. All areas of the heart were accessible from all angles allowing mapping, stimulation and silencing of areas of interest during spontaneous heart beating. Evaluation of radiofrequency ablation techniques and its impact on electrophysiological parameters of different areas of the heart was feasible.

Conclusion: We successfully developed an ex-vivo working heart model without ischemia-reperfusion injury and explanted with an intact left atrium allowing access to all areas of the heart for electrophysiological studies. This model might overcome major limitations of established ex-vivo and in vivo heart models.