Heart surgeries involving bypass to correct coronary and valvular disease are commonly performed procedures. Whilst for the majority, the outcome is favourable, the inevitable temporary interruption of blood flow results in damage to the heart through acute ischaemia-reperfusion injury. Factors such as hypertrophy and diabetes can exacerbate this cardiac injury and worsen clinical outcomes. There is a clear need to protect patients against this peri-operative injury. We have developed novel low-dose carbon monoxide (oCOms) releasing compounds with multimodal signalling effects that target ischaemia-reperfusion injury pathways and demonstrate protection in hearts burdened with hypertrophy. Our study will establish if functional protection of the heart and other organs can be obtained in cardiac surgery. We will trial our pharmacological agents in clinically relevant models of acute myocardial ischaemia and of cardiac bypass surgery in diseased hearts. Ultimately, these compounds will be developed as surgical adjuncts to protect the heart and improve patient outcomes.