Electrical conditioning strategies in myocardial ischemia-reperfusion injury

Although the care of patients presenting with a myocardial infarction (MI) has improved considerably over recent years, mortality in this group is still relatively high. To preserve myocardial function, it is crucial that blood flow is restored as quickly as possible to ischemic areas after an infarction, but this return of flow itself induces detrimental processes that eventually can lead to increased myocardial damage and cell death, a process indicated by the term ischemia-reperfusion injury (IRI). Myocardial IRI is, among others, associated with extensive alterations in energy metabolism, ion homeostasis, bioelectrical signaling pathways and autonomic balance. Current cardioprotective strategies against IRI consist of ischemic, pharmaceutical, stem-cell or mechanical conditioning strategies. Despite substantial pre-clinical progress with these approaches, clinical translation remains challenging. Therefore, alternative approaches are still necessary to reduce the clinical complications associated with IRI. Cardioprotective strategies applying neuromodulation or a form of electrical stimulation may provide for such an angle. It is the goal of this review to provide insight into the molecular and electrical consequences of IRI in the myocardium. Moreover, conditioning strategies that use neuromodulation or a form of electrical stimulation that are of interest for cardioprotection against IRI will be highlighted and explored. • Ischemia-reperfusion injury (IRI) is a major clinical problem in cardiac ischemia. • Present cardioprotective therapies insufficiently protect ischemia patients for IRI. • IRI is associated with metabolic, autonomic and bioelectrical adaptations. • Electrical or neuronal conditioning can increase cardioprotection against IRI. • Future studies should mimic real-world complexity and assess clear clinical endpoints.