SIGMAR1 and ischemia: Although not many studies have discussed that Sig-1R stimulation can protect the injured myocardium post-ischemia–reperfusion by reducing apoptosis and improving endothelial integrity, Sig-1R agonists were administered before ischemic events in all these studies, potentially confounding the distinction between preventive and therapeutic effects and deviating from clinical reality, thereby reducing the translational relevance of such findings.