Cardiopulmonary bypass (CPB) technology has been widely utilized in cardiac surgery since the 1950s, enabling a bloodless surgical field and a motionless heart while maintaining systemic perfusion, particularly to vital organs such as the brain [1]. Nevertheless, myocardial ischemia/reperfusion (I/R) injury remains an inevitable consequence in all patients undergoing cardiac surgery involving aortic cross-clamping and subsequent reperfusion. Despite significant progress in reducing myocardial I/R injury through improved surgical techniques, perioperative monitoring, and cardioprotective strategies, new challenges remain [2,3]. These challenges are driven by the increasing complexity of surgeries and the growing number of critically ill patients. This highlights the urgent need to further refine cardioprotective strategies and to conduct deeper mechanistic studies on I/R injury to improve clinical outcomes.

Myocardial I/R injury involves two distinct but interrelated processes—ischemia and reperfusion—each contributing to a complex set of pathophysiological changes, such as oxidative stress, calcium overload, mitochondrial dysfunction, and neuroinflammation, which ultimately lead to cardiomyocyte death [4,5]. Among these, the reperfusion injury salvage kinase (RISK) pathway and the survival activating factor enhancement (SAFE) pathways are key signaling mechanisms that regulate apoptosis and dysfunction after myocardial I/R injury. Evidence suggests that the effectiveness of cardioprotective strategies depends on the integrity of these pathways in both healthy and failing hearts [[6], [7], [8]]. Caveolin-3 (Cav3) is a member of the caveolin family and predominantly located in the plasma membrane of cardiomyocytes as a structural protein for caveolae [9]. Cav3 can orchestrate various receptors, such as opioid and adenosine receptors, and modulate including RISK and SAFE pathways contributing to myocardial I/R injury, arrhythmia, and heart failure [[10], [11], [12], [13]]. Accumulating studies have demonstrated that the decrease of Cav3 leads to disruption of mitochondrial function, inflammatory reaction, and calcium homeostasis, thereby exacerbating cardiomyocyte death, whereas such an effect is substantially restored by Cav3 overexpression or stability [[14], [15], [16]]. Therefore, modulation of Cav3 expression has been recognized as a promising therapeutic strategy for alleviating both chronic heart disease and myocardial I/R injury [9,17]. However, the majority of studies on Cav3 have been conducted in animal models, and the interaction between Cav3 and key signaling pathways involved in myocardial I/R injury, as well as its functional role in human cardiac tissue, remains to be fully elucidated.

To address these questions, we obtained human atrial myocardium tissues prior to ischemia and 30 min following myocardial reperfusion from patients undergoing scheduled cardiac surgery. We evaluated the expression levels of Cav3, pro-survival kinases, and apoptosis-related proteins, and examined the correlations among these factors. This study aims to determine whether Cav3 are associated with myocardial I/R injury in cardiac surgery, as well as to elucidate the underlying potential molecular mechanisms.