Gastrodin exerts perioperative myocardial protection by improving mitophagy through the PINK1/Parkin pathway to reduce myocardial ischemia-reperfusion injury

•We hypothesized that GAS could repair mitochondrial damage and regulate autophagy.•Male C57BL/6 mice and H9C2 cells survived in I/R and H/R injury after GAS treatment.•MI area diminished and cardiac function improved in GAS-treated mice with MIRI.•Viability increased and cardiomyocyte injury was alleviated in GAS-treated cells.•GAS could be a perioperative myocardial protective agent via PINK1/Parkin pathway. Although blood flow is restored after treatment of myocardial infarction (MI), myocardial ischemia and reperfusion (I/R) can cause cardiac injury, which is a leading cause of heart failure. Gastrodin (GAS) exerts protective effects against brain, heart, and kidney I/R. However, its pharmacological mechanism in myocardial I/R injury (MIRI) remains unclear. GAS regulates autophagy in various diseases, such as acute hepatitis, vascular dementia, and stroke. We hypothesized that GAS could repair mitochondrial damage and regulate autophagy to protect against MIRI. Male C57BL/6 mice and H9C2 cells were subjected to I/R and hypoxia-reoxygenation (H/R) injury after GAS administration, respectively, to assess the impact of GAS on cardiomyocyte phenotypes, heart, and mitochondrial structure and function. The effect of GAS on cardiac function and mitochondrial structure in patients undergoing cardiac surgery has been observed in clinical practice. The effects of GAS on cardiac structure and function, mitochondrial structure, and expression of related molecules in an animal model of MIRI were evaluated using immunohistochemical staining, enzyme-linked immunosorbent assay (ELISA), transmission electron microscopy, western blotting, and gene sequencing. Its effects on the morphological, molecular, and functional phenotypes of cardiomyocytes undergoing H/R were observed using immunohistochemical staining, real-time quantitative PCR, and western blotting. GAS significantly reduces myocardial infarct size and improves cardiac function in MIRI mice in animal models and increases cardiomyocyte viability and reduces cardiomyocyte damage in cellular models. In clinical practice, myocardial injury was alleviated with better cardiac function in patients undergoing cardiac surgery after the application of GAS; improvements in mitochondria and autophagy activation were also observed. GAS primarily exerts cardioprotective effects through activation of the PINK1/Parkin pathway, which promotes mitochondrial autophagy to clear damaged mitochondria. GAS can promote mitophagy and