Cellular and Molecular Mechanism of Cardiac Regeneration: A Comparison of Newts, Zebrafish, and Mammals.

Cardiovascular disease is the leading cause of death worldwide. Current palliative treatments can slow the progression of heart failure, but ultimately, the only curative treatment for end-stage heart failure is heart transplantation, which is only available for a minority of patients due to lack of donors' hearts. Explorative research has shown the replacement of the damaged and lost myocardium by inducing cardiac regeneration from preexisting myocardial cells. Lower vertebrates, such as the newt and zebrafish, can regenerate lost myocardium through cardiomyocyte proliferation. The preexisting adult cardiomyocytes replace the lost cells through subsequent dedifferentiation, proliferation, migration, and re-differentiation. Similarly, neonatal mice show complete cardiac regeneration post-injury; however, this regenerative capacity is remarkably diminished one week after birth. In contrast, the adult mammalian heart presents a fibrotic rather than a regenerative response and only shows signs of partial pathological cardiomyocyte dedifferentiation after injury. In this review, we explore the cellular and molecular responses to myocardial insults in different adult species to give insights for future interventional directions by which one can promote or activate cardiac regeneration in mammals.

Novel method for electrode-tissue contact measurement with multi-electrode catheters.

Aims: With multi-electrode catheters, measuring contact force (CF) on each electrode is technically challenging. Present electrical methods, like the electrical coupling index (ECI) may yield false positive values in pulmonary veins. We developed a novel method that measures electrode-interface resistance (IR) by applying a very local electrical field between neighbouring catheter electrodes while measuring voltage between each catheter electrode and a skin patch. The aim of this study was to evaluate the new IR method to measure electrode-tissue contact. Methods and results: In vitro, effects of remote high-impedance structures were studied. In addition, both ECI and IR were directly compared with true electrode-tissue CF. In five pigs, the influence of high-impedance pulmonary tissue on ECI and IR was investigated while navigating the free floating catheter into the caval veins. Inside the left atrium (LA), IR was directly compared with CF. Finally, multi-electrode IR measurements in the LA and inferior pulmonary vein (IPV) were compared. In vitro, IR is much less affected by remote high-impedance structures than ECI (3% vs. 32%). Both IR and ECI strongly relate to electrode-tissue CF (r2 = 0.84). In vivo, and in contrast to ECI, IR was not affected by nearby pulmonary tissue. Inside the LA, a strong relation between IR and CF was found. This finding was confirmed by simultaneous multi-electrode measurements in LA and IPV. Conclusion: Data of the present study suggest that electrode-tissue contact affects the IR while being highly insensitive to remote structures. This method facilitates electrode-tissue contact measurements with circular multi-electrode ablation catheters.