Sodium octanoate attenuates early post-resuscitation renal injury after hemorrhagic-induced cardiac arrest in a porcine model

Hemorrhage is the most common cause of traumatic cardiac arrest (TCA), and post-resuscitation renal injury remains a challenging clinical research focus. Sodium octanoate has been reported to exert protective effects in models of cerebral, cardiac, and intestinal injury. To investigate the effects of sodium octanoate on post-resuscitation renal injury, we established a porcine model of controlled hemorrhage-induced cardiac arrest, which simulates the ischemic injury of TCA. A total of 18 pigs were enrolled as experimental subjects and divided into three groups: SHAM group (n = 6), TCA group (n = 6), and Sodium octanoate (SO) group (n = 6). The SHAM group underwent anesthesia only, with endotracheal intubation and arterial/venous cannulation. In the TCA group, in addition to the procedures performed in the SHAM group, a TCA model was established by withdrawing blood via the femoral artery using a blood pump and reinfusing it through the femoral vein for resuscitation. In the SO group, after the TCA model was established, sodium octanoate was intravenously infused at a total dose of 30 mg/kg, starting 5 min after return of spontaneous circulation (ROSC), with the infusion completed within 1 h. Resuscitation parameters and survival outcomes were recorded for all groups. Serum creatinine and blood urea nitrogen levels were measured at baseline and at multiple time points after resuscitation. Euthanasia was performed 24 h post-resuscitation, and renal tissue samples from the same anatomical location were collected to evaluate histopathological changes, expression of proteins associated with pyroptosis, and levels of inflammatory cytokines. All animals were successfully resuscitated and remained alive at 24 h post-resuscitation. Following TCA model establishment, serum creatinine and blood urea nitrogen levels increased in both the TCA and SO groups. At 4 and 24 h post-resuscitation, SCr levels were significantly lower in the SO group than in the TCA group (both P < 0.05). BUN levels were significantly lower in the SO group than in the TCA group at all time points post-resuscitation (all P < 0.01). At 24 h post-resuscitation, renal tissue levels of NGAL, KIM-1, NLRP3, caspase-1, GSDMD-N, IL-1β, and IL-18 were significantly lower in the SO group than in the TCA group (all P < 0.05). Histopathological examination revealed prominent inflammatory cell infiltration and focal cellular necrosis in the TCA group, whereas the SO group treated with sodium octanoate exhibited only minimal inflammatory cell infiltration with no significant necrosis. Furthermore, at 2 and 4 h post-resuscitation, HR, MAP, and CO differed significantly between the TCA and SO groups (all P < 0.05). At 4 h post-resuscitation, Lac levels were significantly lower in the SO group than in the TCA group ( P < 0.05). This study suggests that sodium octanoate may attenuate early renal injury at 24 h post-resuscitation in a porcine model of controlled hemorrhage-induced cardiac arrest. The potential mechanism may involve the modulation of inflammasome-associated inflammatory signaling, leading to reduced inflammatory response and cellular necrosis. Sodium octanoate shows potential therapeutic value for early renal injury following resuscitation from TCA.