Rationale and design of the RESTORE trial: A multicenter, randomized, double-blinded, parallel-group, placebo-controlled trial to evaluate the effect of Shenfu injection on myocardial injury in STEMI patients after primary PCI. American heart journal BACKGROUND:The mortality following ST-segment elevation myocardial infarction (STEMI) remains substantial in the reperfusion era. Shenfu injection, as a traditional Chinese herbal formula, can alleviate ischemia-reperfusion injury through multiple pharmacologic effects. However, no robust data are available regarding the role of Shenfu injection in reducing infarct size for patients with STEMI undergoing primary percutaneous coronary intervention (PPCI). METHODS/DESIGN:This RESTORE trial is a multicenter, randomized, double-blind, parallel-group, placebo-controlled trial (NCT04493840). A total of 326 eligible patients with first-time anterior STEMI undergoing PPCI within 12 h of symptom onset will be enrolled from 10 centers in mainland China. Patients are randomized in a 1:1 fashion to receive either intravenous Shenfu injection (80mL Shenfu injection + 70mL 5% glucose injection) or placebo group (150mL 5% glucose injection) before reperfusion and followed by once a day until 5 days after PPCI. The primary end point is infarct size assessed by cardiac magnetic resonance (CMR) imaging 5±2 days after PPCI. The major secondary end points include enzymatic infarct size, microvascular obstruction, intramyocardial hemorrhage, left ventricular volume and ejection fraction assessed by CMR, as well as cardiovascular events at 30 days. CONCLUSIONS:The RESTORE trial is sufficiently powered to demonstrate the clinical effects of Shenfu injection on myocardial injury in STEMI patients undergoing PPCI in the contemporary era. 10.1016/j.ahj.2023.02.005

Role of Excessive Mitochondrial Fission in Seawater Immersion Aggravated Hemorrhagic Shock-Induced Cardiac Dysfunction and the Protective Effect of Mitochondrial Division Inhibitor-1. Antioxidants & redox signaling Seawater immersion significantly aggravated organ dysfunction following hemorrhagic shock, leading to higher mortality rate. However, the effective treatment is still unavailable in clinic. Mitochondria were involved in the onset and development of multiple organ function disorders; whether mitochondria participate in the cardiac dysfunction following seawater immersion combined with hemorrhagic shock remains poorly understood. Hence, we investigated the role and possible mechanism of mitochondria in seawater immersion combined with hemorrhage shock-induced cardiac dysfunction. Mitochondrial fission protein dynamin-related protein 1 (Drp1) was activated and translocated from the cytoplasm to mitochondria in the heart following seawater immersion combined with hemorrhagic shock, leading to excessive mitochondrial fission. Excessive mitochondrial fission disrupted mitochondrial function and structure and activated mitophagy and apoptosis. At the same time, excessive mitochondrial fission resulted in disturbance of myocardial structure and hemodynamic disorders and ultimately provoked multiple organ dysfunction and high mortality. Further studies showed that the mitochondrial division inhibitor mitochondrial division inhibitor-1 can significantly reverse Drp1 mitochondrial translocation and inhibit mitochondrial fragmentation, reactive oxygen species (ROS) accumulation, mitophagy, and apoptosis and then protect circulation and vital organ functions, prolonging animal survival. Our findings indicate that Drp1-mediated mitochondrial fission could be a novel therapeutic targets for the treatment of seawater immersion combined with hemorrhagic shock. Drp1 mitochondrial translocation played an important role in the cardiac dysfunction after seawater immersion combined with hemorrhage shock. Drp1-mediated excessive mitochondrial fission leads to cardiac dysfunction due to the mitochondrial structure and bioenergetics impairment. 10.1089/ars.2022.0167

Incidence and risk factors for acute kidney injury after traumatic hemorrhagic shock: A 10-year retrospective cohort study. Journal of nephrology BACKGROUND:Acute kidney injury (AKI) is a common complication of traumatic hemorrhagic shock. The risk factors for AKI after traumatic hemorrhagic shock remain unclear. The aim of this study was to investigate the risk factors for AKI after traumatic hemorrhagic shock. METHODS:This was a ten-year retrospective cohort study of patients who experienced traumatic hemorrhagic shock between January 2013 and April 2023. Patient characteristics and clinical data were recorded for 417 patients. The outcome was the occurrence of AKI, defined as a serum creatinine increase of ≥ 0.3 mg/dL (≥ 26.5 μmol/L) within 48 h, or an increase to 1.5 times the baseline, or a urine volume of < 0.5 mL/(kg h.). Risk factors for AKI were tested by logistic regression models. RESULTS:The incidence of AKI after traumatic hemorrhagic shock was 29.3% (122/417 patients). Multivariable analysis revealed that the independent risk factors for AKI included age (OR, 1.048; 95% CI, 1.022-1.074; p < 0.001), B-type natriuretic peptide (OR, 1.002; 95% CI, 1.000-1.004; p = 0.041), sepsis (OR, 4.536; 95% CI, 1.651-12.462; p = 0.030) and acute myocardial injury (OR, 2.745; 95% CI, 1.027-7.342; p = 0.044). Road traffic accidents (OR, 0.202; 95% CI, 0.076-0.541; p = 0.001), mean arterial pressure (OR, 0.972; 95% CI, 0.950-0.995; p = 0.017), and base excess (OR, 0.842; 95% CI, 0.764-0.929; p = 0.001) were negatively correlated with AKI. The area under the receiver operating characteristic (ROC) curve for prediction by this model was 0.85 (95% CI, 0.81-0.90). CONCLUSION:The incidence of AKI after traumatic hemorrhagic shock was 29.3% in our series. Indicators of blood perfusion, sepsis and acute myocardial injury may be independent risk factors for AKI after traumatic hemorrhagic shock. Early detection and effective intervention on these risk factors could reduce the occurrence of AKI and improve outcomes. 10.1007/s40620-024-02035-1