Artemisinin alleviates cardiac and cerebral injury after cardiopulmonary resuscitation in pigs by regulating the HMGB1/TLR4/NF-κB mediated inflammatory pathway.

Artemisinin (Art), a sesquiterpene lactone for malaria therapy, attenuates ischemia-reperfusion-induced inflammation in vital organs. This study explored its protective effects and molecular mechanisms against cardiac and cerebral injury in male white pigs after cardiac arrest (CA)/cardiopulmonary resuscitation (CPR). Twenty-two pigs were randomized into sham (n = 6), CPR (n = 8), and Art (CPR + Art, n = 8) groups. A CPR model was established via ventricular fibrillation in the latter two groups, with Art intravenously administered to the Art group post return of spontaneous circulation (ROSC). Hemodynamics, blood gas, cardiac function, cardio-cerebral injury markers, neurological deficit score (NDS), inflammatory cytokines, and HMGB1/TLR4/NF-κB pathway protein expression were compared among groups. No intergroup differences were observed in baseline indices and coronary perfusion pressure during resuscitation (P>0.05), while the Art group had a higher 24-h survival rate (100%) than the CPR group (75%). Compared with the sham group, both the CPR and Art groups exhibited elevated heart rate, reduced blood pressure, decreased PaO₂ and pH, and increased lactic acid levels post-CA/CPR, indicative of acidosis. However, the Art group presented superior hemodynamic profiles, improved post-resuscitation cardiac function, reduced cardio-cerebral injury markers, and lower NDS compared with the CPR group (P < 0.05). We also found that Art downregulated the expression of cardio-cerebral tissue inflammatory cytokines and HMGB1/TLR4/NF-κB pathway proteins (P < 0.05). Collectively, Art treatment facilitates hemodynamic recovery and exerts a protective effect against CA/CPR-induced cardio-cerebral injury. The underlying mechanism may involve the inhibition of CA/CPR triggered inflammatory response via suppressing the HMGB1/TLR4/NF-κB signaling pathway.