Metabolic Profiles of the second and third windows of ischemic preconditioning

There have been numerous studies on the differences between the first window of ischemic preconditioning (IPC) and late IPC, i.e. the second window of IPC. Recently our group has shown the presence of a third window of IPC, which is induced by 6 episodes of non lethal ischemia over 3 days. This model differs from classical second window IPC, induced by 1 or 2 episodes of non lethal ischemia, followed 24 hr. later by a longer period of ischemia. The underlying molecular mechanisms mediating the second and third windows of IPC are very different, but both paradigms of IPC appear to affect myocardial metabolism. The goal of this study was to provide a global analysis of the metabolic profile of these two late IPC models, using a metabolomic approach based on liquid chromatography‐mass spectrometry (LC‐MS) and gas chromatography‐mass spectrometry (GC‐MS) techniques. Myocardial samples from the ischemic section of porcine hearts subjected to second and third window IPC were compared against sham controls. Out of 287 assessed metabolites, there were more changes in metabolic pathways noted in third window (119 metabolites) than second (24 metabolites), but surprisingly only 7 metabolites were common to both models. The results of this study confirm the importance of metabolic pathways mediating late IPC, and again illustrate major differences between the third and second windows of IPC.