Ex situ heart perfusion: a novel model for drug validation and translation

Ex situ heart perfusion (ESHP) was first developed in the 19th century by the German physician Oskar Langendorff. In recent years, ESHP has been critical to the development of donation after circulatory determination of death (DCD) programmes around the globe. ESHP has potential uses that extend far beyond transplantation. Here, we argue that ESHP, and more broadly all ex situ organ perfusion, should be utilised to perform first-in-human studies using turned down donor hearts and explanted recipient hearts from transplantation. This model would enable significantly earlier testing of novel therapeutics in human hearts, with minimal risk to patients. Widespread adoption of this model could streamline drug discovery pipelines, by enabling inefficacious therapeutics to be abandoned earlier in the drug development process. This model is particularly attractive given the high proportion of medicines that fail in stage II and stage III clinical trials due to a lack of efficacy. Development of this model will be dependent on prolonging ex situ perfusion times. Collaboration between industry, academics and clinicians will be needed to ensure successful widespread adoption of this model.