Professor Massimo Caputo and Professor Saadeh Suleiman

Despite significant improvement in our understanding of triggers and mediators of cardiac cellular death during reperfusion injury, cardioprotective strategies of the developing heart remain suboptimal. One reason for this is that interventions are designed and tested using normal, healthy hearts, not considering developmental stages and disease-induced cardiac remodelling which involves cellular, metabolic, molecular, structural and functional changes. To address disease remodelling in neonates, human and animal cardiac tissue was used to investigate molecular characteristics associated with different pathologies.

One project involved investigating molecular remodelling in the hearts of chronically hypoxic fetal sheep as a model for cyanotic paediatric patients. Infarction induced cardiac remodelling into failure in rats has been investigated, and similar experiments in piglets are planned. Hearts from these experimental models will be used to test and optimise the efficacy of different cardioplegic interventions using ex-vivo and in-vivo studies. In the meantime, a clinically relevant healthy piglet model to investigate the cardioprotective efficacy of sildenafil when used as an additive to cardioplegia at different stages of development has been utilised.

An additional approach is to identify targets that are involved in triggering regeneration during development, and the potential use of the extracellular matrix protein agrin in therapies to repair damage in clinically relevant experimental models and in human hearts is being investigated.