Ex Situ Heart Perfusion as a Platform for Therapeutic Intervention: An Experimental Journey

Abstract

In this thesis, our endeavors into the optimization of ex situ heart perfusion (ESHP) for therapeutic purposes are outlined. In the first part of this thesis, steps toward optimization of ESHP to improve preservation are highlighted. These steps include the design of a perfusion protocol to enable extended normothermic ESHP, the validation of a novel device capable of assessing function during unloaded perfusion, and the identification of candidate biomarkers for quality assessment during hypothermic ESHP. The second part of this thesis focusses on the potential for ESHP to serve as a platform for therapeutic intervention. We explored this by conducting numerous literature reviews and conducted a proof-of-principle experimental study to assess whether it is possible to use lipid nanoparticles as a vector for delivery of mRNA to myocardial cells. In the discussion of this thesis, we reflect up future prospects of this promising technology.