Enhancing the recovery potential of the unloaded heart via ?-adrenergic receptor signalling Chronic HF of diverse pathologic origin is one major cause of morbidity and mortality worldwide especially affecting the population of the western world. Ventricular Assist Devices (VADs) are used mainly to support the circulation of patients with end-stage HF as a “bridge to transplantation”. In selected patients not eligible for a heart transplant, more complex VAD systems are permanently implanted as “destination therapy”. Ten years ago first reports emerged of functional recovery of a subpopulation of patients on mechanical support. Since then, increasing efforts have started to investigate this phenomenon and look for possible implicated factors, reliable indicators of recovery, factors that induce long-term functional improvement and additive treatment options that may contribute to a better understanding of the capacity of a failing heart to recover. The importance of ?-adrenergic receptor signalling pathway as a key modulator of myocardial function in disease and recovery has been clearly demonstrated and first attempts at integrating these findings into therapeutic concepts are being tested in clinical trials.
The administration of novel pharmacological and gene based therapies concomitant with the implantation of an assist device may open up further options to increase the use of VADs as “bridge-to-recovery”. We currently investigate effects of ?-adrenergic receptor agonist treatment as well as viral-mediated gene delivery of an agent facilitating adrenergic signalling in the model of heterotopic heart transplantation, especially focusing on the possibility to limit atrophy as one detrimental process occurring in the assisted, unloaded heart. Under this project we aim at characterizing the functional implications and molecular mechanism of unloading-induced atrophic remodelling as well as the benefit resulting from potential prevention via enhanced ?-adrenergic receptor signalling. Approaching these aspects both on an in vivo and in vitro level, the techniques we use are small animal microsurgery, hemodynamic physiology measurements, immunohistochemistry and advanced molecular biology all available in the laboratory.