Salvianolic Acid B Preserves Myocardial Viability and Extends the Preservation Window of Mouse Hearts During Static Cold Storage

Background: Heart transplantation remains the definitive therapy for end-stage heart failure, but its success critically depends on optimal donor heart preservation. Although the University of Wisconsin (UW) solution is the clinical gold standard, its safe storage window for hearts is limited to 4–6 h. Extending this static cold storage (SCS) window represents a critical challenge. We hypothesized that Salvianolic acid B (SalB), a primary bioactive compound in Salvia miltiorrhiza with potent antioxidant and cardioprotective properties, could serve as an effective pharmacological additive to UW solution. Methods: Isolated mouse hearts were subjected to SCS at 4 °C for varying durations (4, 8, and 10 h) in either standard UW solution or UW solution supplemented with 0.8 mg/mL SalB. Myocardial injury was assessed via cardiac enzyme leakage (BNP, CK-MB, LDH), oxidative stress markers, sterile inflammation, and histopathology. The regulatory roles of SalB on apoptosis and autophagic flux were further evaluated, utilizing the autophagy inhibitor 3-methyladenine (3-MA) to establish mechanistic causality. Results: Hearts preserved in SalB-supplemented UW solution exhibited significantly ameliorated histopathological damage, reduced cold ischemia-induced enzyme efflux, and suppressed oxidative stress compared to standard UW solution. Notably, hearts preserved for 8 h with SalB maintained structural and biochemical integrity comparable to those stored for only 4 h in standard UW solution. Mechanistic investigations revealed that SalB treatment orchestrates a pro-survival shift by significantly reducing cardiomyocyte apoptosis and robustly enhancing autophagic flux to maintain cellular homeostasis. The abrogation of autophagy by 3-MA effectively reversed these cardioprotective benefits. Conclusions: Supplementing UW solution with SalB effectively prolongs the structural and biochemical preservation of donor hearts during cold storage up to 8–10 h. By mitigating ischemia–reperfusion injury via the targeted modulation of autophagic flux, SalB highlights its strong translational potential as a robust pharmacological additive for heart transplantation.