Sodium octanoate alleviates cardiac and cerebral injury after traumatic cardiac arrest in a porcine model.

INTRODUCTION: Traumatic cardiac arrest (TCA) is a severe condition with a high mortality rate, and patients who survive from TCA face a poor prognosis due to post-resuscitation injury, including cardiac and cerebral injury, which remains a serious challenge. Sodium octanoate has shown protective effects against various diseases. The present study aims to investigate sodium octanoate's protective effects against cardiac and cerebral injury after TCA in a porcine model. METHODS: The study included a total of 22 male domestic pigs divided into three groups: Sham group (n = 7), TCA group (n = 7), and sodium octanoate (SO) group (n = 8). Hemorrhage was initiated via the right femoral artery by a blood pump at a rate of 2 ml·kg-1·min-1 to establish TCA model. The Sham group underwent only endotracheal intubation and arteriovenous catheterization, without experiencing the blood loss/cardiac arrest/resuscitation model. At 5 min after resuscitation, the SO group received a continuous sodium octanoate infusion while the TCA group received the same volume of saline. General indicators were monitored, and blood samples were collected at baseline and at different time points after resuscitation. At 24 h after resuscitation, pigs were sacrificed, and heart and brain were obtained for cell apoptosis detection, iron deposition staining, oxidative stress detection, and the expression of ferroptosis-related proteins (ACSL4 and GPX4). RESULTS: Sodium octanoate significantly improved mean arterial pressure, cardiac output and ejection fraction induced by TCA. Serum biomarkers of cardiac and cerebral injury were found to increase at all time points after resuscitation, while sodium octanoate significantly reduced their levels. The apoptosis rates of cardiomyocytes and cerebral cortex cells in the SO group were significantly lower than in the TCA group, along with a reduced area of iron deposition staining. The sodium octanoate also reduced oxidative stress and down-regulated ferroptosis which was indicated by protein level alteration of ACSL4 and GPX4. CONCLUSION: Our study's findings suggest that early infusion of sodium octanoate significantly alleviates post-resuscitation cardiac and cerebral injury in a porcine model of TCA, possibly through inhibition of cell apoptosis and GPX4-mediated ferroptosis. Therefore, sodium octanoate could be a potential therapeutic strategy for patients with TCA.

ECMO management for severe pulmonary embolism with concurrent cerebral hemorrhage: a case report.

Background: Acute pulmonary embolism (APE) is a common and potentially fatal cardiovascular disease that can lead to sudden cardiac arrest in severe cases. When conventional cardiopulmonary resuscitation measures fail to achieve the return of spontaneous circulation (ROSC) in patients with APE, venoarterial extracorporeal membrane oxygenation (ECMO) becomes a viable therapeutic option. As an advanced life support treatment, ECMO ensures the perfusion of critical organs, providing sufficient time for interventions necessary for ROSC. Case introduction: We report the case of a patient who experienced cardiac arrest due to pulmonary embolism. During the treatment, the patient received two sessions of external cardiopulmonary resuscitation (ECPR) as supportive care and experienced cerebral hemorrhage. Ultimately, the patient improved and was discharged following support from extracorporeal membrane oxygenation (ECMO), careful anticoagulation strategies, and intervention with balloon pulmonary angioplasty. Conclusion: ECMO can serve as an important life support technology for patients with severe APE. Through a cautious anticoagulation therapy, not only was the ECMO support successfully maintained but also was further deterioration of cerebral hemorrhage effectively prevented. For patients with concurrent main pulmonary artery embolism and bleeding, balloon pulmonary angioplasty may be an option.

The establishment and evaluation of a swine model of deinagkistrodon acutus snakebite envenomation.

OBJECTIVE: To establish a preclinical large-animal model of Deinagkistrodon acutus snakebite envenomation and evaluate its feasibility. METHODS: The venom of D. acutus (0 mg/kg, 1 mg/kg, 2 mg/kg, 5 mg/kg, or 10 mg/kg) was injected into the left biceps femoris of 11 male pigs. Then, the circumferences of the limbs were regularly measured, and changes in muscle injury biomarkers, blood parameters, coagulation function, vital organ function and injury biomarkers were regularly detected. At 24 h after venom injection, the animals were euthanized, and the pathological damage to the vital organs mentioned above was evaluated. RESULTS: The two pigs receiving 10 mg/kg and 5 mg/kg snake venom died at 8 h and 12 h after injection, respectively. The remaining pigs were equally divided into 0 mg/kg, 1 mg/kg, and 2 mg/kg snake venom groups, and all of them survived to 24 h after injection. Compared with the pigs receiving 0 mg/kg snake venom, the pigs receiving 1 mg/kg or 2 mg/kg snake venom exhibited significant abnormities, including limb swelling; increased muscle injury biomarker creatine kinase (CK) and coagulation function indicators prothrombin time and D-dimer; and decreased blood routine indicator platelet and coagulation function indicator fibrinogen. Moreover, significant abnormalities in myocardial and cerebral function and injury biomarkers in the heart, brain, liver, kidney and intestine were also observed. In particular, the abnormalities mentioned above were significantly obvious in those pigs receiving 2 mg/kg snake venom. Pathological evaluation revealed that the morphology of muscle, heart, brain, liver, kidney, and intestine in those pigs receiving 0 mg/kg snake venom was normal; however, pathological damage was observed in those pigs receiving 1 mg/kg and 2 mg/kg snake venom. Similarly, the pathological damage was more severe in those pigs receiving 2 mg/kg snake venom. CONCLUSION: The intramuscular injection of 2 mg/kg D. acutus venom seems to be an optimal dose for examining the preclinical efficacy of existing and novel therapeutics for treating D. acutus envenomation in pigs.

SULFORAPHANE ALLEVIATES POSTRESUSCITATION LUNG PYROPTOSIS POSSIBLY VIA ACTIVATING THE NRF2/HO-1 PATHWAY.

ABSTRACT: Introduction: Sulforaphane (SFN), known as the activator of the nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway, has been proven to protect the lung against various pathological stimuli. The present study aimed to investigate the effect of SFN on lung injury induced by systemic ischemia reperfusion after cardiac arrest and resuscitation. Methods: After animal preparation, 24 pigs were randomly divided into sham group (n = 6), cardiopulmonary resuscitation group (CPR, n = 9), or CPR + SFN group (n = 9). The experimental model was then established by 10 min of cardiac arrest followed by 6 min of CPR. Once spontaneous circulation was achieved, a dose of 2 mg/kg of SFN diluted in 20 mL of saline was intravenously infused with a duration of 5 min. During 4 h of observation after resuscitation, extravascular lung water index (ELWI), pulmonary vascular permeability index (PVPI), and oxygenation index were regularly evaluated. At 24 h after resuscitation, lung tissues were harvested to evaluate the score of lung histopathological injury, the activity of superoxide dismutase, the contents of malondialdehyde, IL-1ß, and IL-18, and the expression levels of NOD-like receptor pyrin domain 3, cleaved caspase 1, gasdermin D (GSDMD), GSDMD N-terminal, Nrf2, and HO-1. Results: During CPR, spontaneous circulation was achieved in six and seven pigs in the CPR and CPR + SFN groups, respectively. After resuscitation, the indicators of lung injury (ELWI, PVPI, and oxygenation index) were all better in the CPR + SFN group than in the CPR group, in which the differences in ELWI and PVPI at 2, and 4 h after resuscitation were significant between the two groups. In addition, SFN significantly reduced lung injury score, improved oxidative imbalance (superoxide dismutase, malondialdehyde), decreased pyroptosis-related proinflammatory cytokines (IL-1ß, IL-18), downregulated pyroptosis-related proteins (NOD-like receptor pyrin domain 3, cleaved caspase 1, GSDMD, GSDMD N-terminal), and activated the Nrf2/HO-1 pathway when compared with the CPR group. Conclusion: SFN produced effective postresuscitation lung protection through alleviating lung pyroptosis possibly via activating the Nrf2/HO-1 pathway in pigs.