Towards the prevention of post cardiac surgery organ failure

Background: Organ injury and dysfunction of the heart and kidneys are common and often life-threatening complications of cardiac surgery with cardiopulmonary bypass. There are no effective prevention strategies. Our recent work on the obesity paradox suggests that baseline metabolic status determines patients’ susceptibility to organ injury.Methods: We have identified three clinical interventions that alter metabolic status in patients, and also have organ protection effects in preclinical models. We propose to evaluate these as organ protection strategies in cardiac surgery in a series of proof of concept randomised controlled trials. We will use the randomisation of patients to different metabolic interventions in these trials to explore the mechanisms underlying our clinical observations. In addition, we will assess whether biomarkers of metabolic status identified in these trials can be used for improved risk stratification and diagnosis of organ injury in cardiac surgery.Value of Results: This programme will explore the mechanisms underlying the obesity paradox and establish whether interventions that alter energy substrate and mitochondrial function pre-surgery have clinical benefits. The insights gained in these trials will improve our understanding of post cardiac surgery organ failure, as well as the obesity paradox observed in other clinical settings.