SIRT1 and ischemia reperfusion injury: Similarly, Nadtochiy et al. comparing SIRT1-deficient (SIRT1+/−) and SIRT1-overexpressing (SIRT1+++) mice in heart ischemic preconditioning (IPC) showed that SIRT1+/−hearts could not be preconditioned properly, whereas SIRT1+++ hearts were endogenously protected against ischemia reperfusion injury and exhibited decreased cytosolic acetylation which was reversible by SIRT1 inhibitor splitomicin [36].